Q95343	Involved in susceptibility to Stevens-Johnson syndrome [MIM:608579]. This is a life-threatening reaction of the skin to particular types of medication. It is characterized by high fever, malaise and blistering exanthema. The more severe form of the disease is referred to as toxic epidermal necrolysis.
Q29846	HLA-B27 is associated with the development of ankylosing spondylitis (AS) [MIM:106300]. AS is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton and is considered the prototype of seronegative spondyloarthropathies (SNSA), which include reactive arthritis (e.g., Reiter's syndrome), psoritic spondylitis, and other spondyloarthropathies (SpA). In the Greek Cypriot population, a restricted number of HLA-B27 subtypes are associated with AS and other B27-related diseases and an elevated frequency of the B*2702 allele in the AS patients is identified. The allele B*2707 seems to have a protective role in this population because it was found only in the healthy controls.
P18464	HLA-B51 is associated with Behcet disease but it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. About 20% of healthy individuals of various ethnic origin carries the HLA-B 51 locus, compared with 50 to 80% of patients. Behcet disease is a systemic disorder of recurrent acute inflammation characterized by 4 major symptoms: oral aphthous ulcers, skin lesions, ocular symptoms and genital ulcerations. Occasionally, inflammation in tissues and organs throughout the body can occur, including the gastrointestinal tract, central nervous system, vascular system, lungs, and kidneys. The etiology of Behcet disease is unclear.
Q29963	Genetic variation in HLA-C is associated with susceptibility to psoriasis 1 (PSORS1) [MIM:177900]. Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. It is characterized by red, scaly skin lesions that are usually found on the scalp, elbows, and knees, and may be associated with severe arthritis. The lesions are caused by hyperproliferative keratinocytes and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age.
P30154	Defects in PPP2R1B might be a cause of some lung and colorectal cancers.
Q00005	Defects in PPP2R2B are the cause of spinocerebellar ataxia type 12 (SCA12) [MIM:604326]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
Q7M2H4	Allelic variation at the HLA-DRB1 locus is a major contributor to genetic predisposition for sarcoidosis [MIM:181000]. Sarcoidosis is a disease of unknown aetiology in which there are chronic inflammatory granulomatous lesions in lymph nodes and other organs.
P01903	Genetic variations in HLA-DRA are associated with susceptibility to hepatitis B virus infection (HBV infection) [MIM:610424]. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection may result in subclinical or asymptomatic infection, acute self-limited hepatitis, or fulminant hepatitis requiring liver transplantation.
P26439	Defects in HSD3B2 are the cause of adrenal hyperplasia type 2 (AH2) [MIM:201810]. AH2 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late onset (NC or LOAH), and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life.
P26439	Mild HSD3B2 deficiency in hyperandrogenic females is associated with characteristic traits of polycystic ovary syndrome, such as insulin resistance and luteinizing hormon hypersecretion.
Q9H2F3	Defects in HSD3B7 are the cause of congenital bile acid synthesis defect type 1 (CBAS1) [MIM:607765]; also known as neonatal progressive intrahepatic cholestasis. CBSA1 is due to a primary defect in bile synthesis leading to progressive liver disease. Clinical features include neonatal jaundice, severe intrahepatic cholestasis, chirrosis.
P78314	Defects in SH3BP2 are the cause of cherubism (CRBM) [MIM:118400]. CRBM is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.
P11171	Defects in EPB41 are the cause of elliptocytosis type 1 (EL1) [MIM:611804]. EL1 is a Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant, hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
P11171	Defects in EPB41 are a cause of hereditary pyropoikilocytosis (HPP) [MIM:266140]. HPP is an autosomal recessive hematologic disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.
Q9UC45	Defects in NT5C3 are the cause of P5N deficiency [MIM:266120]; also called hemolytic anemia due to P5N deficiency or hemolytic anemia due to UMPH1 deficiency. P5N deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stipplig and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.
P49902	Aberration of this enzyme may be related to the urate production in hyperuricemia and gout.
P21589	There is a decrease in the activity of NT5 in B-cell chronic lymphocytic leukemia.
Q676U5	Genetic variations in ATG16L1 are associated with susceptibility to inflammatory bowel disease type 10 (IBD10) [MIM:611081]. IBD is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease (CD) and ulcerative colitis phenotypes. IBD10 individuals show the phenotype characteristic to CD. It may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. CD is commonly classified as autoimmune disease.
Q86U19	The major physiological function of AAT is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE). A hereditary deficiency of AAT, is associated with a 20-30 fold increased risk of developing chronic obstructive pulmonary disease.
Q86U19	Deficiency of the normal inhibitor in individuals homozygous for allele Z or M-Malton can result in the development of chronic emphysema or infantile liver cirrhosis.
Q86U19	Variant Pittsburgh is the cause of bleeding diathesis.
P08697	Defects in SERPINF2 are the cause of alpha-2-plasmin inhibitor deficiency (APLID) [MIM:262850]. APLID is an autosomal recessive disorder resulting in severe hemorrhagic diathesis.
Q9UCC8	Defects in APP are a cause of autosomal dominant Alzheimer disease (AD) [MIM:104300]. AD is the most prevelant form of dementia, characterized by neurofibrillary tangles and amyloid plaques deposition in the brain. Identical lesions occur in the neurons of aged Down syndrome but at an earlier age than in AD. The major constituent of these neuritic plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. Mutations occurring at the beta-amyloid N-terminal, such as the Swedish double mutation, appear to increase levels of beta-amyloid by facilitating beta-secretase cleavage resulting in elevated levels of both beta-APP42 and beta-APP40. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31, are also implicated in AD neuronal death. Alzheimer disease caused by mutations in APP is a rare occurrence and usually causes the familial or early-onset form of the disease (FAD). Flemish-type AD is characterized by, in addition to presenile dementia, cerebral hemorrhaging due to cerebral amyloid angiopathy which is similar to, but distinct from, cerebroarterial amyloidosis Dutch type. Only about 5% of all cases of Alzheimer disease are caused by FAD mutations, the rest are sporadic.
Q9UCC8	Defects in APP are the cause of hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWAD) [MIM:609065]. HCHWAD is characterized by amyloid deposits in cerebral vessels. The principal clinical characteristics are recurring cerebral hemorrhages, sometimes preceded by migrainous headaches or mental cleavage. Beta-APP40 is the predominant form of cerebrovascular amyloid.
Q9UCC8	Defects in APP are the cause of hereditary cerebroarterial amyloidosis Iowa type [MIM:605714]. Hereditary cerebroarterial amyloidosis Iowa type is an autosomal dominant dementia beginning in the sixth or seventh decade of life. The patients have progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. They do not present cerebral hemorrhaging.
Q9NS82	Defects in SLC7A10 may be involved in cystinuria (CSNU) which arises from impaired transport of cystine and dibasic amino acids through the epithelial cells of the renal tubule and gastrointestinal tract. Three types of cystinuria have been described.
Q9NRG9	Defects in AAAS are the cause of achalasia-addisonianism- alacrima syndrome (AAAS) [MIM:231550]; also known as triple-A syndrome or Allgrove syndrome. AAAS is an autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)- resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.
Q8N177	Defects in SERPINA3 may be a cause of chronic obstructive pulmonary disease (COPD) [MIM:107280].
Q9UGJ0	Defects in PRKAG2 are the cause of Wolff-Parkinson-White syndrome (WPWS) [MIM:194200]; also known as preexcitation syndrome. It is the second most common cause of paroxysmal supraventricular tachycardia.
Q9UGJ0	Defects in PRKAG2 are a cause of cardiomyopathy familial hypertrophic with Wolff-Parkinson-White syndrome (CHMWPWS) [MIM:600858]. HCM due to PRKAG2 mutations is probably due to polysaccharide storage in the heart. Defects in PRKAG2 may not be a frequent cause of HCM where no features of pre-excitation are found in affected individuals.
Q9UGJ0	Defects in PRKAG2 are a cause of glycogen storage disease of heart lethal congenital (GSDH) [MIM:261740]; also known as phosphorylase kinase deficiency of heart or congenital nonlysosomal cardiac glycogenosis. GSDH is a rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise.
Q9MYP4	Defects in PRKAG3 are the cause of the RN- phenotype which is associated with excess glycogen content (about 70%) in skeletal muscle. This mutation originated in the hampshire breed pigs and has beneficial effects on meat content but detrimental effects on processing yield. Thus, this mutation is of considerable economic significance in the pig breeding industry.
Q9UDR5	Defects in AASS are the cause of hyperlysinemia [MIM:238700]. Hyperlysinemia is an autosomal recessive condition characterized by hyperlysinemia lysinuria and variable saccharopinuria.
Q0VD83	Genetic variations in APOB48R may be a cause of susceptibility to hypercholesterolemia.
O95477	Defects in ABCA1 are a cause of high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by absence of high density lipoprotein (HDL) cholesterol from plasma, accumulation of cholesteryl esters, premature coronary artery disease (CAD), hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness.
O95477	Defects in ABCA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). HDLD2 is inherited as autosomal dominant trait. It is characterized by moderately low HDL cholesterol, predilection toward premature coronary artery disease (CAD) and a reduction in cellular cholesterol efflux.
Q99758	Defects in ABCA3 are the cause of pulmonary surfactant metabolism dysfunction type 3 (SMDP3) [MIM:610921]; also called pulmonary alveolar proteinosis due to ABCA3 deficiency. Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular non-specific interstitial pneumonitis (NSIP).
P78363	Defects in ABCA4 are the cause of Stargardt disease type 1 (STGD1) [MIM:248200]. STGD is one of the most frequent causes of macular degeneration in childhood. It is characterized by macular dystrophy with juvenile-onset, rapidly progressive course, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. STGD1 inheritance is autosomal recessive.
P78363	Defects in ABCA4 are the cause of fundus flavimaculatus (FFM) [MIM:248200]. FFM is an autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course.
P78363	Defects in ABCA4 may be a cause of age-related macular degeneration type 2 (ARMD2) [MIM:153800]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
P78363	Defects in ABCA4 are the cause of cone-rod dystrophy type 3 (CORD3) [MIM:604116]. CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
P78363	Defects in ABCA4 are the cause of retinitis pigmentosa type 19 (RP19) [MIM:601718]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP19 is characterized by choroidal atrophy. Inheritance is autosomal recessive.
Q86UK0	Defects in ABCA12 are the cause of ichthyosis harlequin (HI) [MIM:242500]; also known as harlequin fetus. HI is a very severe skin disorder in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period.
Q86UK0	Defects in ABCA12 are the cause of ichthyosis lamellar type 2 (LI2) [MIM:601277]; also known as ichthyosis congenita IIB (ICR2B). LI is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. It is one the most severe forms of ichthyoses apparent at birth and persisting throughout life. LI patients are born encased in a tight, shiny, translucent covering called collodion membrane. Over the first weeks of life, the collodion membrane is gradually replaced by generalized large, dark brown, plate-like scales with minimal to no erythroderma. Tautness of facial skin commonly results in ectropion, eclabium and scarring alopecia of the scalp. Common complications are severe heat intolerance and recurrent ear infections.
O75027	Defects in ABCB7 are the cause of X-linked sideroblastic anemia with ataxia (ASAT) [MIM:301310]. ASAT is a recessive disorder characterized by an infantile to early childhood onset of nonprogressive cerebellar ataxia and mild anemia with hypochromia and microcytosis.
O95342	Defects in ABCB11 are the cause of progressive familial intrahepatic cholestasis type 2 (PFIC2) [MIM:601847]. PFIC2 is an inherited liver disease of childhood which is characterized by cholestasis and normal serum gamma-glutamyltransferase activity. Defects in ABCB11 are also found in cases of chronic intrahepatic cholestasis without obvious familial history of chronic liver disease.
O95342	Defects in ABCB11 are the cause of benign recurrent intrahepatic cholestasis type 2 (BRIC2) [MIM:605479]. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration and patients are asymptomatic between episodes, both clinically and biochemically.
O95342	Genetic variations in ABCB11 may play a role in drug- induced cholestasis causing liver damage.
Q09428	Defects in ABCC8 are a cause of leucine-induced hypoglycemia (LIH) [MIM:240800]; also called leucine-sensitive hypoglycemia of infancy. LIH is a rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglicemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine.
Q09428	Defects in ABCC8 are the cause of familial hyperinsulinemic hypoglycemia type 1 (HHF1) [MIM:256450]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or hyperinsulinism. HHF1 is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. It causes nesidioblastosis, a diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Q09428	Defects in ABCC8 are a cause of permanent neonatal diabetes mellitus (PNDM) [MIM:606176]; also called permanent diabetes mellitus of infancy (PDMI). PNDM is a rare form of diabetes characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.
Q09428	Defects in ABCC8 are the cause of transient neonatal diabetes mellitus type 2 (TNDM2) [MIM:610374]. Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to- severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence.
Q09428	Defects in ABCC8 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2, in Northern European Caucasians.
O60706	Defects in ABCC9 are the cause of cardiomyopathy dilated type 1O (CMD1O) [MIM:608569]; also known as dilated cardiomyopathy with ventricular tachycardia. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
P33897	Defects in ABCD1 are the cause of X-linked adrenoleukodystrophy (X-ALD) [MIM:300100]. X-ALD is a peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and "Addison disease only" (ADO) phenotype.
P33897	Microdeletions in ABCD1 are involved in the contiguous ABCD1/DXS1375E deletion syndrome (CADDS) [MIM:300475]. Patients manifest profound neonatal hypotonia, subsequent failure to thrive, and cholestatic liver disease.
P28288	Defects in ABCD3 may be the cause of Zellweger syndrome type 2 (ZWS-2) [MIM:170995]. ZWS-2 is an autosomal recessive disorder due to defective import mechanisms for peroxisomal matrix enzymes. The clinical phenotype includes characteristic facies, progressive neurological dysfunction, liver disease and death in infancy.
Q9BXL1	Overexpressed in macrophages from patients with Tangier disease compared to control macrophages. Expressed in foamy macrophages within the atherosclerotic plaque. May play a role in the cholesterol metabolism of macrophages in vitro and in the atherosclerotic plaque.
Q9H222	Defects in ABCG5 are a cause of sitosterolemia [MIM:210250]; also known as phytosterolemia or shellfish sterolemia. It is a rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.
Q9H221	Genetic variations in ABCG8 can be associated with susceptibility to gallbladder disease type 4 (GBD4) [MIM:611465]. With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries.
Q9H221	Defects in ABCG8 are a cause of sitosterolemia [MIM:210250]; also known as phytosterolemia or shellfish sterolemia. It is a rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.
Q8WTS1	Defects in ABHD5 are the cause of Chanarin-Dorfman syndrome (CDS) [MIM:275630]; also called triglyceride storage disease with impaired long-chain fatty acid oxidation or neutral lipid storage disease with ichthyosis. CDS is an autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non- bullous congenital ichthyosiform erythroderma.
Q9NXZ9	A chromosomal aberration involving ABI1 is a cause of acute leukemias. Translocation t(10;11)(p11.2;q23) with MLL. ABI1 isoform 2 was found to be present in acute leukemia MLL-ABI1 fusion transcript.
P00519	A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia (CML) [MIM:608232]. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Q86WB3	Defects in ACACA are a cause of ACACA deficiency [MIM:200350]; also called ACAC or ACC deficiency. ACACA deficiency is an inborn error of de novo fatty acid synthesis. The disorder is associated with severe brain damage, persistent myopathy and poor growth.
Q9UKU7	Defects in ACAD8 are the cause of isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]. The symptoms of IBDD generally appear until late in infancy or in childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia).
Q9H845	Defects in ACAD9 are a cause of acyl-CoA dehydrogenase family member type 9 deficiency (ACAD9 deficiency) [MIM:611126]. ACAD9 deficiency patients present with episodic liver dysfunction during otherwise mild illnesses or cardiomyopathy, along with chronic neurologic dysfunction.
P28330	Defects in ACADL are the cause of long-chain acyl-CoA dehydrogenase deficiency (LCAD deficiency) [MIM:201460]. LCAD deficiency leads to non-ketotic hypoglycemia.
P11310	Defects in ACADM are the cause of medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) [MIM:201450]. It is an autosomal recessive disease which causes fasting hypoglycemia, hepatic dysfunction, and encephalopathy, often resulting in death in infancy. The disease frequency is one in 13000.
P16219	Defects in ACADS are the cause of short-chain acyl-CoA dehydrogenase deficiency (SCAD deficiency) [MIM:201470]. It is an autosomal recessive disorder resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
P49748	Defects in ACADVL are the cause of very long chain acyl- CoA dehydrogenase deficiency (VLCAD deficiency) [MIM:201475]. VLCAD deficiency is an autosomal recessive disease which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting.
P45954	Defects in ACADSB are the cause of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]; also called 2-methylbutyryl-CoA dehydrogenase deficiency or 2- methylbutyryl glycinuria. SBCADD is an autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features.
Q5EE38	Defects in Acd are the cause of adrenocortical dysplasia (ACD). ACD is a spontaneous autosomal recessive mouse mutant resulting from spontaneous splicing mutation of acd. ACD mice are characterized by developmental defects in organs derived from the urogenital ridge, reduced survival, poor growth, skin hyperpigmentation and adrenal insufficiency. Forty percent of the mutants died within 24 hours. Analysis of E14.5 to E17.5 embryos revealed reduced formation of caudal structure as well as limb defects.
P12821	Genetic variations in ACE may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
P12821	Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
P12821	Genetic variations in ACE can influence susceptibility to diabetic nephropathy [MIM:603933]. Diabetic nephropathy is a kidney disease and resultant kidney function impairment due to the long standing effects of diabetes on the microvasculature (glomerulus) of the kidney. Features include increased urine protein and declining kidney function.
Q15822	Defects in CHRNA2 are the cause of nocturnal frontal lobe epilepsy type 4 (ENFL4) [MIM:610353]. ENFL4 is an autosomal dominant epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking.
P32297	Genetic variations in CHRNA3 may be associated with susceptibility to lung cancer type 2 (LNCR2) [MIM:612052].
P32297	Genetic variations in CHRNA3 may be associated with susceptibility to peripheral arterial occlusive disease type 2 (PAOD2) [MIM:612052]. PAOD results from atherosclerosis of large and medium peripheral arteries, as well as the aorta. Many risk factors contribute to PAOD, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease.
P43681	Defects in CHRNA4 are the cause of nocturnal frontal lobe epilepsy type 1 (ENFL1) [MIM:600513]; also symbolized ADNFLE. ENFL1 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
P30532	Genetic variations in CHRNA5 may be associated with susceptibility to lung cancer type 2 (LNCR2) [MIM:612052].
P02708	Defects in CHRNA1 are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.
P02708	The alpha subunit is the main focus for antibody binding in myasthenia gravis [MIM:254200]. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.
P02708	Defects in CHRNA1 are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
P02708	Defects in CHRNA1 are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
P17787	Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:605375]. ENFL3 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
P11230	Defects in CHRNB1 are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
P11230	Defects in CHRNB1 are a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (ACHRDCMS) [MIM:608931]. ACHRDCMS is a post-synaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance.
Q07001	Defects in CHRND are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.
Q07001	Defects in CHRND are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Q07001	Defects in CHRND are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Q04844	The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis [MIM:254200]. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase- inhibiting drugs.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (ACHRDCMS) [MIM:608931]. ACHRDCMS is a post-synaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance.
P07510	Defects in CHRNG are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. Inheritance can be autosomal dominant, autosomal recessive, or X linked, but autosomal recessive inheritance appears to be most common. Clinical expression is very variable, and, in the severest form, lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia (e.g., chin to sternum, cervical, axillary, humero-ulnar, crural, popliteal, and ankles), and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies-in particular, cleft palate-are frequent.
P07510	Defects in CHRNG are a cause of Escobar syndrome [MIM:265000]; also called Escobar variant multiple pterygium syndrome or nonlethal type multiple pterygium syndrome. Escobar syndrome is a nonlethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis.
P08172	Genetic variations in CHRM2 can influence susceptibility to major depressive disorder (MDD) [MIM:608516]. MDD is one of the most common psychiatric disorders. MDD is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning.
Q15067	Defects in ACOX1 are the cause of pseudoneonatal adrenoleukodystrophy [MIM:264470]; also known as peroxisomal acyl- CoA oxidase deficiency. Pseudo-NALD is a peroxisomal single-enzyme disorder. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very- long chain fatty cids, due to decreased or absent peroxisome acyl- CoA oxidase activity. Peroxisomes are intact and functioning.
Q99424	Absent in patients suffering from Zellweger syndrome.
O60488	Defects in ACSL4 are the cause of non-syndromic mental retardation X-linked type 63 (MRX63) [MIM:300387]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.
O60488	Defects in ACSL4 may be a cause of AMME complex [MIM:300194]; also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;12)(q31;p13) with ETV6.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;12)(q31;p13) with ETV6.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ETV6.
P62736	Defects in ACTA2 are the cause of aortic aneurysm familial thoracic type 6 (AAT6) [MIM:611788]. AATs are characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. They are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
P60709	Defects in ACTB are a cause of juvenile-onset dystonia [MIM:607371]. Dystonia is a movement disorder with a neurological basis, due to disordered tonicity of muscle. It is characterized by sustained involuntary muscle contractions that cause abnormal postures and repetitive movements. It may affect muscles throughout the body (generalized), in certain parts of the body (segmental), or may be confined to particular muscles or muscle groups (focal). Individuals with juvenile-onset dystonia due to ACTB mutations present a complicated phenotype that includes progressive generalized dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.
P68032	Defects in ACTC1 are the cause of cardiomyopathy dilated type 1R (CMD1R) [MIM:102540]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
P68032	Defects in ACTC1 are the cause of cardiomyopathy familial hypertrophic type 11 (CMH11) [MIM:612098]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
P63261	Defects in ACTG1 are the cause of non-syndromic sensorineural deafness autosomal dominant type 20 (DFNA20) [MIM:604717]; also called autosomal dominant deafness type 26 (DFNA26). DFNA20 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q01718	Defects in MC2R are the cause of glucocorticoid deficiency type 1 (GCCD1) [MIM:202200]; also known as familial glucocorticoid deficiency type 1 (FGD1). GCCD1 is an autosomal recessive disorder due to congenital insensitivity or resistance to adrenocorticotropin (ACTH). It is characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency.
O43707	Cytoplasmic localization of ACTN4 may be associated with cancer metastases due to enhanced cell motility.
O43707	Defects in ACTN4 are the cause of focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]. FSGS1 is a common renal lesion characterized by increased urinary protein excretion (proteinuria) and decreasing kidney function (nephrotic syndrome). Renal insufficiency often progresses to end-stage renal disease (ESRD) (also known as end-stage renal failure), a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS1 is defined by the presence of segmental sclerosis in glomeruli, and is seen in all ethnic groups, although it is particularly common in individuals of African descent. FSGS1 occurs as an isolated primary condition or secondary to disorders as HIV infection, obesity, hypertension and diabetes. FSGS1 may also be inherited as a Mendelian trait.
P68133	Defects in ACTA1 are the cause of nemaline myopathy type 3 (NEM3) [MIM:161800]. Nemaline myopathy (NEM) is a form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination. The clinical phenotype is highly variable, with differing age at onset and severity.
P68133	Defects in ACTA1 are a cause of congenital myopathy with excess of thin myofilaments (CM) [MIM:102610].
P68133	Defects in ACTA1 are a cause of congenital myopathy with fiber-type disproportion (CFTD) [MIM:255310]; also known as congenital fiber-type disproportion myopathy (CFTDM). CFTD is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
P37023	Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:600376]; also known as Osler- Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.
Q04771	Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:135100]. FOP is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification in FOP begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible.
Q03154	Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:609924]. ACY1D results in a metabolic disorder manifesting with encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.
P45381	Defects in ASPA are the cause of Canavan disease (CAND) [MIM:271900]; also known as spongy degeneration of the brain. CAND is a rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demeylination that gives rise to a spongy appearance. The clinical features are onset in early infancy, atonia of neck muscles, hypotonia, hyperextension of legs and flexion of arms, blindness, severe mental defect, megalocephaly, and death by 18 months on the average.
O75078	Rearrangements occur in breast and ovarian cancers which involve multiple exons and disrupt the coding region.
Q9BZ11	Defects in ADAM33 may be a cause of susceptibility to asthma.
O00116	Defects in AGPS are the cause of rhizomelic chondrodysplasia punctata type 3 (RCDP3) [MIM:600121]. RCDP3 is characterized by rhizomelic shortening of femur and humerus, vertebral disorders, cataract, cutaneous lesions and severe mental retardation.
P00813	Defects in ADA are the cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:102700]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA-SCID is an autosomal recessive form accounting for about 50% of non-X-linked SCIDs. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.
P00813	In hereditary hemolytic anemia, the level of this enzyme in erythrocytes increases 50-70 times.
Q8NI60	Defects in CABC1 are a cause of coenzyme Q10 deficiency [MIM:607426]; also known as primary CoQ10 deficiency. Coenzyme Q10 deficiency patients present a progressive neurological disorder with cerebellar atrophy, developmental delay, and hyperlactatemia.
Q8NI60	Defects in CABC1 are the cause of spinocerebellar ataxia autosomal recessive type 9 (SCAR9) [MIM:612016]; also known as autosomal recessive cerebellar ataxia type 2 (ARCA2). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR9 is an autosomal recessive form characterized by gait ataxia and cerebellar atrophy with slow progression and few associated features. Patients can manifest brisk tendon reflexes and Hoffmann sign, mild psychomotor retardation, mild axonal degeneration of the sural nerve, exercise intolerance and elevated serum lactate.
Q96PN6	Genetic variations in ADCY10 are associated with absorptive hypercalciuria type 2 (HCA2) [MIM:143870]. Absorptive hypercalciuria (AH) is a common cause of calcium oxalate nephrolithiasis. Clinically, AH is characterized by intestinal hyperabsorption of calcium in the presence of normal serum calcium and immunoreactive PTH (iPTH). It is often accompanied by low bone mineral density (BMD), particularly of the lumbar spine. About 50% of patients with AH present with a family history of calcium oxalate nephrolithiasis and hypercalciuria.
Q15848	Defects in ADIPOQ are the cause of adiponectin deficiency [MIM:605441]. The result is a very low concentration of plasma adiponectin. Decreased adiponectin plasma levels are associated with obesity insulin resistance, and diabetes type 2.
Q9UHA1	Polymorphic forms of ADRB2 could impart some form of nocturnal asthma.
P12235	Defects in SLC25A4 are a cause of autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 2 (PEOA2) [MIM:609283]. Progressive external ophthalmoplegia (PEO) is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of ptosis and weakness of the extraocular muscles and exercise intolerance. The typical histological findings are ragged-red fibers (RRFs) with focal cytochrome c oxidase deficiency in patients' skeletal muscle.
P55197	A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with MLL/HRX. The result is a rogue activator protein.
P55197	A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
P55198	A chromosomal aberration involving MLLT6 is associated with acute leukemias. Translocation t(11;17)(q23;q21) with MLL/HRX. The result is a rogue activator protein.
Q13015	A chromosomal aberration involving MLLT11 is found in acute leukemias. Translocation t(1;11)(q21;q23) with MLL.
P42568	A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with MLL/HRX. The result is a rogue activator protein.
P55196	A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein.
Q8N556	Overexpressed in prostate carcinoma, expression levels positively correlate with aggressiveness of the disease.
P51825	A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with MLL/HRX. The result is a rogue activator protein.
P51816	Defects in AFF2 are the cause of FRAXE [MIM:309548]. FRAXE is an X-linked form of mental retardation. Loss of FMR2 expression is correlated with FRAXE CCG(N) expansion. Normal individuals have 6-35 copies of the repeat, whereas cytogenetically positive, developmentally delayed males have more than 200 copies and show methylation of the associated CPG island.
Q9UHB7	A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a MLL-AFF4 fusion protein.
Q5I7T1	Defects in ALG10B may reduce susceptibility to acquired long QT syndrome (aLQTS) [MIM:152427]. It is a cardiac anomaly characterized by a paradoxical life-threatening cardiac rhythm disturbance.
P06280	Defects in GLA are the cause of Fabry disease (FD) [MIM:301500]. FD is a rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaoslyceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.
Q8N302	Defects in AGGF1 are a cause of Klippel-Trenaunay syndrome (KTS) [MIM:149000]. KTS is a congenital disease characterized by malformations of capillary (98% of KTS patients), venous (72%) and lymphatic (11%) vessels, and bony and soft tissue hypertrophy that leads to large cutaneous hemangiomata with hypertrophy of the related bones and soft tissues.
O00253	Defects in AGRP may be a cause of autosomal dominant obesity [MIM:601665].
P30556	Defects in AGTR1 are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
Q8N157	Defects in AHI1 are the cause of Joubert syndrome type 3 (JBTS3) [MIM:608629]. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS3 shows minimal extra central nervous system involvement and appears not to be associated with renal dysfunction.
Q9GZX7	Defects in AICDA are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2) [MIM:605258]. HIGM2 is characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. HIGM2 causes the absence of Ig class switch recombination (CSR), the lack of Ig somatic hypermutations, and lymph node hyperplasia caused by the presence of giant germinal centers.
O14862	Defects in AIM2 may be a cause of microsatellite unstable colon cancers.
Q9NZN9	Defects in AIPL1 are the cause of Leber congenital amaurosis type 4 (LCA4) [MIM:604393]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
O00170	Defects in AIP are a cause of pituitary adenoma predisposition (PAP) [MIM:102200].
O00170	Defects in AIP are a cause of familial isolated pituitary adenoma (FIPA) [MIM:102200].
O00170	Defects in AIP are a cause of growth hormone-secreting pituitary adenoma [MIM:102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma.
O00170	Defects in AIP are a cause of ACTH-secreting pituitary adenoma [MIM:219090]; also known as pituitary Cushing disease. Cushing disease is a condition associated with increased blood cortisol resulting from adrenocorticotropic hormone (ACTH)- producing pituitary tumors that are resistant to glucocorticoid negative feedback.
O43918	Defects in AIRE are a cause of autoimmune poly- endocrinopathy candidiasis ectodermal dystrophy (APECED) [MIM:240300]; also known as autoimmune polyglandular syndrome type I (APS-1). APECED is an autosomal recessive disease characterized by: (1) autoimmune polyendocrinopathies: hypoparathyroidism, adrenocortical failure, IDDM, gonadal failure, hypothyroidism, pernicious anemia, and hepatitis; (2) chronic mucocutaneous candidiasis; (3) ectodermal dystrophies: vitiligo, alopecia, keratopathy, dystrophy of dental enamel, nails and tympanic membranes. In addition, a high proportion of patients develop squamous cell carcinoma of the oral mucosa. The disease is reported worldwide but is exceptionally prevalent among the Finnish population (incidence 1:25000) and the Iranian jews (incidence 1:9000).
O43918	Most of the mutations alter the nucleus-cytoplasm distribution of AIRE and disturb its association with nuclear dots and cytoplasmic filaments. Most of the mutations also decrease transactivation of the protein. The HSR domain is responsible for the homomultimerization activity of AIRE. All the missense mutations of the HSR and the SAND domains decrease this activity, but those in other domains do not. The AIRE protein is present in soluble high-molecular-weight complexes. Mutations in the HSR domain and deletion of PHD zinc fingers disturb the formation of these complexes.
P51857	Defects in AKR1D1 are the cause of congenital bile acid synthesis defect type 2 (CBAS2) [MIM:235555]; also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.
Q02952	Antibodies to the C-terminal of gravin can be produced by patients with myasthenia gravis (MG).
Q9Y6Y2	Defects in AKAP9 are the cause of long QT syndrome type 11 (LQT11) [MIM:611820]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to excercise or emotional stress. They can present with a sentinel event of sudden cardiac death in infancy.
P31751	Alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas.
Q64362	Defects in Aktip are a cause of embryonic death in homozygous animals. Death occurs at about 10 days of development. Symptoms include loss of left-right asymmetry, malformation of the developing brain and of the spinal cord, syndactyly and polydactyly. Heterozygous animals are characterized by polydactyly and thymic hyperplasia.
P51648	Defects in ALDH3A2 are the cause of Sjoegren-Larsson syndrome (SLS) [MIM:270200]. SLS is an autosomal recessive neurocutaneous disorder characterized by a combination of severe mental retardation, spastic di- or tetraplegia and congenital ichthyosis (increased keratinization). Ichthyosis is usually evident at birth, neurologic symptoms appear in the first or second year of life. Most patients have an IQ of less than 60. Additional clinical features include glistening white spots on the retina, seizures, short stature and speech defects.
P30038	Defects in ALDH4A1 are the cause of hyperprolinemia type II (HPII) [MIM:239510]. HPII is characterized by the accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. The disorder may be causally related to neurologic manifestations, including seizures and mental retardation.
P20292	Genetic variations in ALOX5AP may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
P20292	Haplotypes HapA and HapB are associated with susceptibility to myocardial infarction [MIM:608557].
P49419	Defects in ALDH7A1 are the cause of pyridoxine-dependent epilepsy (PDE) [MIM:266100]. PDE is characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride.
Q9P157	Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.
Q9P157	A variant structure of albumin could lead to increased binding of zinc resulting in an asymptomatic augmentation of zinc concentration in the blood [MIM:194470].
P04075	Defects in ALDOA are the cause of aldolase A deficiency [MIM:611881]; also known as aldoA deficiency or red cell aldolase deficiency. Aldolase A deficiency is an autosomal recessive disorder associated with hereditary hemolytic anemia.
P05062	Defects in ALDOB are the cause of hereditary fructose intolerance (HFI) [MIM:229600]. HFI is an autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.
P15121	In diabetes and galactosemia, increased AR activity leads to high levels of sorbitol and galactitol, respectively, in the cells of many tissues. Accumulation of sugar alcohols has been shown to cause osmotic cataracts in the lens. AR is also thought to play a key role in diabetic complications of three other target tissues, namely, nerve, kidney and retina.
P84996	Defects in GNAS are the cause of GNAS hyperfunction [MIM:139320]. This condition is characterized by increased trauma- related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms.
P84996	Defects in GNAS are a cause of ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]; also known as adrenal Cushing syndrome due to AIMAH. AIMAH is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands.
P84996	Genetic variations in GNAS are the cause of pseudohypoparathyroidism type 1B (PHP1B) [MIM:603233]. PHP1B is characterized by parathyroid hormone (PTH)-resistant hypocalcemia and hyperphosphatemia. Patients affected with PHP1B have normal activity of the product of GNAS, lack developmental defects characteristic of AHO, and typically show no other endocrine abnormalities besides resistance to PTH. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.
P84996	Defects in GNAS may be a cause of colorectal cancer (CRC) [MIM:114500].
Q9BV10	Defects in ALG12 are the cause of congenital disorder of glycosylation type 1G (CDG1G) [MIM:607143]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9BT22	Defects in ALG1 are the cause of congenital disorder of glycosylation type 1K (CDG1K) [MIM:608540]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9H553	Defects in ALG2 are the cause of congenital disorder of glycosylation type 1I (CDG1I) [MIM:607906]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q92685	Defects in ALG3 are the cause of congenital disorder of glycosylation type 1D (CDG1D) [MIM:601110]; also known as carbohydrate-deficient glycoprotein syndrome type IV (CDGS4). CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins.
Q9Y672	Defects in ALG6 are the cause of congenital disorder of glycosylation type 1C (CDG1C) [MIM:603147]; also known as carbohydrate-deficient glycoprotein syndrome type V. CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1C patients have muscular hypotonia, show a delayed statomotor development and are mentally retarded. CDG1C is biochemically characterized by an accumulation of dolichyl pyrophosphate-linked Man(9)GlcNAc(2) in the endoplasmic reticulum.
Q9BVK2	Defects in ALG8 are the cause of congenital disorder of glycosylation type 1H (CDG1H) [MIM:608104]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9H6U8	A chromosomal aberration involving ALG9 is found in a family with bipolar affective disorder. Translocation t(9;11)(p24;q23).
Q9H6U8	Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) [MIM:608776]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9UM73	A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas.
Q9UM73	A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A.
Q9UM73	A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17.
Q8TCU4	Defects in ALMS1 are the cause of Alstrom syndrome (ALMS) [MIM:203800]. Alstrom syndrome is a rare autosomal recessive disorder characterized by progressive cone-rod retinal dystrophy, neurosensory hearing loss, early childhood obesity and type 2 diabetes mellitus. Dilated cardiomyopathy, acanthosis nigricans, male hypogonadism, hypothyroidism, developmental delay and hepatic dysfunction can also be associated with the syndrome.
Q9HCF4	A chromosomal aberration involving ALO17 is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALK.
Q96Q42	Defects in ALS2 are the cause of amyotrophic lateral sclerosis type 2 (ALS2) [MIM:205100]. ALS2 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.
Q96Q42	Defects in ALS2 are the cause of juvenile primary lateral sclerosis (JPLS) [MIM:606353]. JPLS is a neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons of the motor cortex while the lower neurons are unaffected.
Q96Q42	Defects in ALS2 are the cause of infantile-onset ascending spastic paralysis (IAHSP) [MIM:607225]. IAHSP is characterized by progressive spasticity and weakness of limbs.
Q9H161	Defects in ALX4 are the cause of parietal foramina 2 (PFM2) [MIM:609597]; also known as foramina parietalia permagna (FPP). PFM2 is an autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM2 is also a clinical feature of Potocki- Shaffer syndrome.
Q9H161	Involved in Potocki-Shaffer syndrome (PSS) [MIM:601224]. PSS is a contiguous gene syndrome caused by deletion of the 11p11.2 region.
O35137	Defects in Alx4 are the cause of Strong luxoid (lst) phenotype. At heterozygosity lst is characterized by preaxial abnormalities of the hindfeet and, very rarely, of the forefeet. Homozygotes show preaxial polydactyly of all four limbs, reductions and duplications of the radius, absence of the tibia, craniofacial defects, reduction of the pubis, and dorsal alopecia.
Q9UHK6	Defects in AMACR are the cause of alpha-methylacyl-CoA racemase deficiency (AMACRD) [MIM:604489]. AMACRD results in elevated plasma concentrations of pristanic acid C27-bile-acid intermediates. It can be associated with polyneuropathy, retinitis pigmentosa, epilepsy.
Q9UHK6	Defects in AMACR are the cause of congenital bile acid synthesis defect type 4 (CBAS4) [MIM:214950]; also known as cholestasis, intrahepatic, with defective conversion of trihydroxycoprostanic acid to cholic acid or trihydroxycoprostanic acid in bile. Clinical features include neonatal jaundice, intrahepatic cholestasis, bile duct deficiency and absence of cholic acid from bile.
Q9NP70	Defects in AMBN are found in patients with ameloblastomas.
Q99217	Defects in AMELX are the cause of amelogenesis imperfecta hypoplastic type 1 (AIH1) [MIM:301200]. AIH1 is a X-linked defect of dental enamel formation. Teeth have only a thin layer of enamel with normal hardness. The thinness of the enamel makes the teeth appear small.
Q9Y4X0	Defects in AMMECR1 may be a cause of AMME complex [MIM:300194]; also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome.
Q16671	Defects in AMHR2 are the cause of persistent Muellerian duct syndrome type 2 (PMDS-2) [MIM:261550]. PMDS-2 is a form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males.
Q6UKI2	Defects in AMN could be a cause of a canine form of megaloblastic anemia 1 (MGA1).
Q9BXJ7	Defects in AMN are a cause of recessive hereditary megaloblastic anemia 1 (MGA1) [MIM:261100]; also referred to as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS). MGA1 is due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.
P23109	Defects in AMPD1 are the cause of adenosine monophosphate deaminase deficiency muscle type (AMPDDM) [MIM:102770]. AMPDDM is a metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue.
Q01432	Defects in AMPD3 are the cause of adenosine monophosphate deaminase deficiency erythrocyte type (AMPDDE) [MIM:102772]. AMPDDE is a metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady- state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders.
P49418	Antibodies against AMPH are detected in patients with stiff-man syndrome, a rare disease of the central nervous system characterized by progressive rigidity of the body musculature with superimposed painful spasms.
P15144	Defects in ANPEP may be a cause of various types of leukemia or lymphoma.
P30533	In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis.
P54802	Defects in NAGLU are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB) [MIM:252920]; also known as Sanfilippo syndrome B. MPS-IIIB is an autosomal recessive disorder whose clinical features are severe mental deterioration but mild somatic manifestations in childhood, and death in the second decade. Biochemically, this disease is characterized by undegraded or partially degraded heparan sulfate which accumulates in lysosomes and is excreted in urine.
P10275	Genetic variation in AR can be responsible of androgenetic alopecia (AGA) [MIM:109200].
P10275	Defects in AR are the cause of androgen insensibility syndrome (AIS) [MIM:300068]; previously known as testicular feminization syndrome (TFM). It can be complete (CAIS) when external genitalia are phenotypically female; or partial (PAIS) when external genitalia are substantively ambiguous or mild (MAIS) when external genitalia are normal male or nearly so.
P10275	Defects in AR are the cause of X-linked spinal and bulbar muscular atrophy (SBMA) [MIM:313200]; also known as Kennedy disease. In SBMA patients the number of Gln ranges from 40 to 52. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
P10275	Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor.
P10275	Defects in AR may be the cause of infertility male syndrome [MIM:308370]; also called androgen insensitivity. It is characterized by azoospermia, elevated testosterone and luteinizing hormone plasma levels and an abnormal androgen receptor.
P10275	Defects in AR are the cause of Reifenstein syndrome [MIM:312300]; also known as partial androgen insensitivity. The features of this form of male pseudohermaphroditism are hypospadias, hypogonadism, gynecomastia, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance.
P15207	Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).
P03950	Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:611895]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.
Q9BY76	Found to be highly expressed in the early stages of collagen-induced arthritis (CIA).
Q9BY76	Serum levels of ANGPTL4 are significantly lower in patients with diabetes type 2 than those in healthy subjects, suggesting that decreased ANGPTL4 could be a causative factor of this disease.
Q9BY76	Produced in ischemic tissues in conditions such as critical leg ischemia. In tumors, ANGPTL4 could be produced in the hypoxic areas surrounding necrotic regions. High levels could be produced in tumor cells of conventional renal cell carcinoma. This molecule therefore seems to be a marker of conventional renal cell carcinoma.
Q9Z1P8	Elevated levels of expression in models of obesity and diabetes.
P01019	Defects in AGT are associated with susceptibility to essential hypertension [MIM:145500]. Hypertension also occurs in 5-7% of all pregnancies where it is a leading cause of maternal, fetal and neonatal morbidity and mortality. Among pregnancy- induced hypertension cases, severe pre-eclampsia [MIM:189800] is characterized by the development of hypertension and proteinuria after the 20th week of pregnancy and is the most distinctive, life-threatening form.
P01019	Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
P16157	Defects in ANK1 are a cause of hereditary spherocytosis (HS) [MIM:182900]. Inheritance can be autosomal dominant or recessive.
Q01484	Defects in ANK2 are the cause of long QT syndrome type 4 (LQT4) [MIM:600919]; also known as sick sinus syndrome with bradycardia. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress. LQT4 displays many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature.
Q9HCJ1	Defects in ANKH are the cause of chondrocalcinosis 2 (CCAL2) [MIM:118600]. Chondrocalcinosis is a common cause of joint pain and arthritis caused by calcium deposition in articular cartilage and the presence of calcium hypophosphate crystals in synovial fluid, cartilage and periarticular soft tissue. CCAL2 inheritance is autosomal dominant.
Q9HCJ1	Defects in ANKH are the cause of craniometaphyseal dysplasia Jackson type (CMDJ) [MIM:123000]. CMDJ is a rare autosomal dominant skeletal disorder characterized by abnormal bone formation and mineralization in membranous as well as endochondral bones. Progressive thickening of the bones can cause narrowing of cranial foramina and can lead to severe visual and neurological impairment, such as facial palsy and deafness.
Q9JHZ2	Defects in Ankh are the cause of a generalized, progressive form of arthritis. In ank mice hydroxyapatite crystals develop in articular surfaces and synovial fluid leading to joint space narrowing, cartilage erosion, and formation of bony outgrowths or osteophytes that cause fusion and joint immobility and destruction.
P0C0T2	Defects in Anks6 are the cause of polycystic kidney disease (cy). Heterozygous cy rats are characterized by progressive formation and enlargement of cysts in kidneys.
P20594	Defects in NPR2 are the cause of acromesomelic dysplasia Maroteaux type (AMDM) [MIM:602875]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDM is an autosomal recessive form characterized by axial skeletal involvement with wedging of vertebral bodies. In AMDM all skeletal elements are present but show abnormal rates of linear growth.
P70180	Defects in Npr3 are the cause of a number of skeletal- overgrowth phenotypes, Longjohn (Lgj), Longjohn-2J (Lgj-2J) and Strigosus (Stri). These are all recessive conditions characterized by an elongated body, thoracic kyphosis, arachnodactyly, and sacral and/or tail kinks, but no significant changes in craniofacial structures.
P01008	Defects in SERPINC1 are the cause of antithrombin III deficiency (AT-III deficiency) [MIM:107300]. AT-III deficiency is an important risk factor for hereditary thrombophilia [MIM:188050], a multifactorial trait characterized by recurrent thrombosis and abnormal platelet aggregation in response to various agents. AT-III deficiency is inherited as an autosomal dominant disorder, in which affected individuals are prone to develop serious spontaneous thrombosis. AT-III deficiency is classified into 4 types. Type I: characterized by a 50% decrease in antigenic and functional levels. Type II: has defects affecting the thrombin-binding domain. Type III: alteration of the heparin- binding domain. Plasma AT-III antigen levels are normal in type II and III. Type IV: consists of miscellaneous group of unclassifiable mutations.
P01008	AT-III Basel, Tours/Alger/Amiens/Toyama, Rouen-1, -2, -3 and -4 have decreased (or lack) heparin-binding properties.
P01008	AT-III Hamilton, Glasgow/Sheffield/Chicago, Northwick- Park/Milano-1, Pescara, Denver/Milano-2, and Utah are deprived of inhibitory activity.
P58335	Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures.
P58335	Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility.
P50995	Antibodies against ANXA11 are present in sera from patients with various autoimmune diseases, predominantly in sera from patients with rheumatoid arthritis, systemic lupus erythematosus, or Sjoegren syndrome.
O76027	ANXA9 is one of the target molecules recognized by autoantibodies in patients with pemphigus vulgaris. Pemphigus vulgaris is a rare, autoimmune skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion.
P21397	Defects in MAOA are the cause of Brunner syndrome [MIM:300615]. Brunner syndrome is a form of X-linked non- dysmorphic mild mental retardation. Male patients are affected by a syndrome of borderline mental retardation and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior.
Q10567	Deletion of the AP1B1 gene may play a role in the tumorigenesis of meningiomas.
P56377	Defects in AP1S2 are the cause of X-linked mental retardation 59 (MRX59) [MIM:300630]. Mental retardation has a prevalence of about 2%-3% in developed populations and is more common in males than in females. Mutations in genes on the X chromosome are known to be a major cause of familial X-linked mental retardation. MRX59 consists of a mild-to-profound mental retardation. Other features includes hypotonia early in life and delay in walking.
P05549	Defects in TFAP2A are the cause of branchiooculofacial syndrome (BOFS) [MIM:113620]; also known as branchial clefts with characteristic facies, growth retardation, imperforate nasolacrimal duct, and premature aging or lip pseudocleft- hemangiomatous branchial cyst syndrome. BOFS is a rare autosomal dominant cleft palate craniofacial disorder with variable expressivity. The major features include cutaneous anomalies, ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies.
Q92481	Defects in TFAP2B are the cause of Char syndrome (CHAR) [MIM:169100]. CHAR is an autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.
O00203	Defects in AP3B1 are the cause of Hermansky-Pudlak syndrome 2 (HPS2) [MIM:608233, 203300]. Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype and patients with HPS2 have an increased susceptibility to infections.
Q9Z1T1	Defects in Ap3b1 are the cause of the autosomal recessive phenotype 'pearl' (pe). Pearl mice exhibit hypopigmentation, lysosomal secretion abnormalities, and platelet-dense granules with reduced levels of adenine nucleotides and serotonin. The changes in platelets lead to prolonged bleeding. Additionally, pearl mice exhibit reduced sensitivity in the dark-adapted state.
P25054	Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:175100]; which includes also Gardner syndrome (GS). FAP and GS contribute to tumor development in patients with uninherited forms of colorectal cancer. FAP is characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.
P25054	APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.
P25054	Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:135290]; also called familial infiltrative fibromatosis (FIF). It is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.
P25054	Defects in APC are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).
P25054	Defects in APC are a cause of Turcot syndrome [MIM:276300]. Turcot syndrome is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.
P02647	Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant.
P02647	Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I.
P02647	Defects in APOA1 are a cause of systemic non-neuropathic amyloidosis [MIM:105200]; also known as amyloidosis VIII or Ostertag-type amyloidosis. It is an autosomal dominant disorder characterized by generalized amyloid deposition.
P09813	Defects in Apoa2 are the cause of senescence accelerated mouse (SAM), the senile amyloid is a mutated apolipoprotein A-II.
Q6Q788	Defects in APOA5 are a cause of susceptibility to familial hypertriglyceridemia [MIM:145750]. It is a coronary heart disease risk factor. On a regular diet the patient demonstrates increased plasma VLDL. Plasma triglycerides are persistently increased, while plasma cholesterol and phospholipids are usually within normal limits.
Q6Q788	Defects in APOA5 are a cause of hyperlipoproteinemia type 5 [MIM:144650]. Hyperlipoproteinemia type 5 is characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin-dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A) [MIM:232200].
P08519	Elevated plasma concentrations of apo(a) and its naturally occurring proteolytic fragments are correlated with atherosclerosis. Homology with plasminogen kringles IV and V is thought to underlie the atherogenicity of the protein, because the fragments are competing with plasminogen for fibrin(ogen) binding.
P14417	Elevated plasma concentrations of apo(a) and its naturally occurring proteolytic fragments are correlated with atherosclerosis. Homology with plasminogen kringles IV and V is thought to underlie the atherogenicity of the protein, because the fragments are competing with plasminogen for fibrin(ogen) binding.
Q13787	Defects in APOB are a cause of familial hypobetalipoproteinemia (FHBL) [MIM:107730]. FHBL is a genetically heterogeneous autosomal co-dominant disorder, associated with reduced plasma concentrations of apoB, LDL and VLDL. Heterozygotes for FHBL are usually asymptomatic with LDL cholesterol and apoB- 100 concentrations less than 50% of those in normal plasma. Homozygotes have extremely low plasma LDL cholesterol and apoB-100 concentrations, and clinical presentation may vary from no symptoms to severe gastrointestinal and neurological dysfunction similar to abetalipoproteinemia [MIM:200100].
Q13787	Defects in APOB are a cause of familial ligand-defective apolipoprotein B-100 (FDB) [MIM:144010]. FDB is a dominantly inherited disorder of lipoprotein metabolism leading to hypercholesterolemia and increased proneness to coronary artery disease (CAD). The plasma cholesterol levels are dramatically elevated due to impaired clearance of LDL particles by defective APOB/E receptors.
Q13787	Defects in APOB associated with defects in other genes (polygenic) can contribute to hypocholesterolemia.
P02655	Defects in APOC2 are the cause of hyperlipoproteinemia type IB [MIM:207750]. It is an autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis.
P02656	Defects in APOC3 may be a cause of hyperalphalipoproteinemia [MIM:143470]. Affected individuals show high levels of alpha-lipoprotein (high density lipoprotein/HDL).
P02649	Defects in APOE are a cause of hyperlipoproteinemia type III [MIM:107741]; also known as familial dysbetalipoproteinemia. Individuals with hyperlipoproteinemia type III, are clinically characterized by xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for APOE*2 alleles. More severe cases of hyperlipoproteinemia type III have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE*4 variant are at higher risk of CAD.
P02649	The APOE*4 allele is associated with late onset Alzheimer disease 2 (AD2) [MIM:104310]. The APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.
P02649	Defects in APOE are a cause of sea-blue histiocyte disease [MIM:269600]; also called sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.
P02649	Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:611771]. LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians.
Q7Z2E3	Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.
Q7Z2E3	Defects in APTX are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy. Coenzyme Q10 deficiency due to APTX mutations is typically associated with cerebellar ataxia.
P07741	Defects in APRT are the cause of APRT deficiency [MIM:102600]; also known as 2,8-dihydroxyadenine urolithiasis. It is an autosomal recessive disease characterized by renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.
P41181	Defects in AQP2 are a cause of autosomal nephrogenic diabetes insipidus, type I (AD-NDI) [MIM:125800]. It is characterized by excessive water drinking (polydypsia) and urine excretion (polyuria).
P05089	Defects in ARG1 are the cause of argininemia [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.
Q15052	Defects in ARHGEF6 are the cause of non-syndromic mental retardation X-linked type 46 (MRX46) [MIM:300436]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.
O43307	Defects in ARHGEF9 are a cause of startle disease with epilepsy (STHEE) [MIM:300607]; also known as hyperekplexia with epilepsy. Startle disease is a genetically heterogeneous neurologic disorder. STHE is characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli.
O15013	Defects in ARHGEF10 are the cause of slowed nerve conduction velocity (SNCV) [MIM:608236]. Affected individuals present a reduction in nerve conduction velocities without any clinical signs of peripheral or central nervous system dysfunction. SNCV inheritance is autosomal dominant.
Q9NZN5	A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with MLL.
Q5SW96	Defects in LDLRAP1 are the cause of autosomal recessive hypercholesterolemia (ARH) [MIM:603813]. ARH is a disorder caused by defective internalization of LDL receptors (LDLR) in the liver. ARH has the clinical features of familial hypercholesterolemia (FH) [MIM:143890] homozygotes, including severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. LDL receptor (LDLR) activity measured in skin fibroblasts is normal, as the LDL binding ability.
Q969Q4	Defects in ARL11 may be a cause of susceptibility to chronic lymphocytic leukemia (CLL) [MIM:151400].
Q9H0F7	Defects in ARL6 are a cause of Bardet-Biedl syndrome type 3 (BBS3) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease.
P04424	Defects in ASL are the cause of arginosuccinicaciduria [MIM:207900]. Arginosuccinicaciduria is an autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness.
P0C7Q2	Defects in ARMS2 influence susceptibility to age-related macular degeneration type 8 (ARMD8) [MIM:611313]. ARMD is the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch's membrane. ARMD is likely to be a mechanistically heterogeneous group of disorders, and the specific disease mechanisms that underlie the vast majority of cases are currently unknown. However, a number of studies have suggested that both genetic and environmental factors are likely to play a role.
P08168	S-antigen induces autoimmune uveitis.
Q28281	S-antigen induces autoimmune uveitis.
Q28281	Defects in SAG may be the cause of generalized progressive retinal atrophy (gPRA) in some breeds.
P10523	S-antigen induces autoimmune uveitis.
P10523	Defects in SAG are the cause of Oguchi disease 1 [MIM:258100]; also known as stationary night blindness Oguchi type-1. It is a form of recessively inherited stationary night blindness.
P20443	S-antigen induces autoimmune uveitis.
P79260	S-antigen induces autoimmune uveitis.
P15887	S-antigen induces autoimmune uveitis.
P15289	Defects in ARSA are a cause of metachromatic leukodystrophy (MLD) [MIM:250100]. MLD is a disease characterized by intralysosomal storage of cerebroside-3-sulfate, as well as in the myelin membranes. Whereas storage occurs in many cells, the disease almost exclusively affects oligodendrocytes. Patients suffer from a progressive demyelination, which causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Several years after the onset of the disease, patients die in a decerebrated state. Three forms of the disease can be distinguished according to the age at onset: late-infantile, juvenile and adult.
P15289	Arylsulfatase A activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. MSD is a disorder characterized by decreased activity of all known sulfatases. MSD is due to defects in SUMF1 resulting in the lack of post- translational modification of a highly conserved cysteine into 3- oxoalanine. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
P33727	Defects in ARSB are the cause of mucopolysaccharidosis type VI (MPS-VI). MPS-VI has been described in Siamese cats.
P15848	Defects in ARSB are the cause of mucopolysaccharidosis type VI (MPS-VI) [MIM:253200]; also known as Maroteaux-Lamy syndrome. MPS-VI is an autosomal recessive disorder characterized by the accumulation of dermatan sulfate in lysosomes. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities. A wide variation in clinical severity is observed.
P15848	Arylsulfatase B activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. MSD is a disorder characterized by decreased activity of all known sulfatases. MSD is due to defects in SUMF1 resulting in the lack of post- translational modification of a highly conserved cysteine into 3- oxoalanine. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
P50430	Defects in Arsb are the cause of mucopolysaccharidosis type VI (MPS-VI).
P51690	Defects in ARSE are the cause of chondrodysplasia punctata X-linked recessive type 1 (CDPX1) [MIM:302950]. CDP is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. CDPX1 is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. This disease can also be induced by inhibition with the drug warfarin.
O00192	Gene deleted in velo-cardio-facial syndrome (VCFS); it is hemizygous in all VCFS patients with interstitial deletions. This hemizygosity may play a role in the etiology of some of the phenotypes associated with VCFS characterized by a wide spectrum phenotypes, including conotruncal heart defects, cleft palate and facial dysmorphology.
Q96QS3	Defects in ARX are the cause of lissencephaly X-linked type 2 (LISX2) [MIM:300215]; also known as lissencephaly X-linked with ambiguous genitalia (XLAG). LISX2 is a classic type lissencephaly associated with abnormal genitalia. LISX2 patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
Q96QS3	Defects in ARX are a cause of X-linked infantile spasm syndrome (ISSX) [MIM:308350]; also known as X-linked West syndrome. The disorder is characterized by infantile spasms, hypsarrhythmia on EEG, and developmental arrest leading to severe to profound mental retardation.
Q96QS3	Defects in ARX are a cause of myoclonic epilepsy X-linked with intellectual disability and spasticity (XMEIDS) [MIM:300432]. XMEIDS is characterized by myoclonic epilepsy with generalized spasticity and intellectual deficit.
Q96QS3	Defects in ARX are a cause of Partington syndrome (PRTS) [MIM:309510]; also known as X-linked syndromic mental retardation 1 (MRXS1). PRTS is characterized by mental retardation, episodic dystonic hand movements, and dysarthria.
Q96QS3	Defects in ARX are the cause of non-syndromic mental retardation X-linked type 54 (MRX54) [MIM:300419]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.
Q96QS3	Defects in ARX are the cause of agenesis of corpus callosum with abnormal genitalia (ACC with abnormal genitalia) [MIM:300004]. ACC with abnormal genitalia consists of a brain and genital malformations syndrome.
Q96KY8	N-acetylation polymorphism is determined by a low or high NAT activity in liver, it has been implicated in the action and toxicity of amine-containing drugs, and in the susceptibility to bladder cancer and systemic lupus erythematosus. This isozyme is responsible for this polymorphism.
P0C7U1	ASAH2B/ASAH2L shows reduced expression with increasing age, reduced expression in females across ages, and further reduction in late-onset Alzheimer disease (LOAD) patients. This reduction is even more pronounced in patients with an affected mother.
Q13510	Defects in ASAH1 are the cause of Farber disease (FD) [MIM:228000]; also known as Farber lipogranulomatosis. This sphingolipid disease is characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, marked accumulation of ceramide in lysosomes, and death by three years of age.
P17405	Defects in SMPD1 are the cause of Niemann-Pick disease type A (NPA) [MIM:257200]; also referred to as the classical infantile form. Niemann-Pick disease is a clinically and genetically heterogeneous recessive disorder. It is caused by the accumulation of sphingomyelin and other metabolically related lipids in the lysosomes, resulting in neurodegeneration starting from early life. Patients may show xanthomas, pigmentation, hepatosplenomegaly, lymphadenopathy and mental retardation. Niemann-Pick disease occurs more frequently among individuals of Ashkenazi Jewish ancestry than in the general population. NPA is characterized by very early onset in infancy and a rapidly progressive course leading to death by three years.
P17405	Defects in SMPD1 are the cause of Niemann-Pick disease type B (NPB) [MIM:607616]; also referred to as the visceral form. NPB has little if any neurologic involvement and patients may survive into adulthood.
Q9BZE9	Chromosomal aberrations involving ASPSCR1 are recurrent in alveolar soft part sarcoma (ASPS) [MIM:606243]. Translocation t(X;17)(p11;q25) with TFE3 forms a ASPSCR1-TFE3 fusion protein.
Q9BZE9	A chromosomal aberration involving ASPSCR1 may be a cause of papillary renal cell carcinoma (PRCC) [MIM:605074].
P20933	Defects in AGA are the cause of aspartylglucosaminuria (AGU) [MIM:208400]. AGU is an inborn lysosomal storage disease. Clinical features of AGU include mild to severe mental retardation manifesting from the age of 2, coarse facial features and mild connective tissue abnormalities. This recessively inherited disease is overrepresented in the Finnish population.
Q9NVT6	Defects in ASPM are the cause of microcephaly primary type 5 (MCPH5) [MIM:608716]; also known as true microcephaly or microcephaly vera. Microcephaly is defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits. This entity is inherited as autosomal recessive trait.
Q96KQ4	Defects in PPP1R13B may be a cause of breast cancers. It is overexpressed in many patients suffering from breast carcinomas and expressing a wild-type TP53 protein.
Q13625	Defects in TP53BP2 may be involved in breast cancer. TP53BP2 is down-regulated in many patients suffering from breast carcinomas and expressing a wild-type TP53 protein. Overexpressed in lung cancer cell lines.
P14568	Defects in ASS1 are the cause of a bovine form of citrullinemia.
P00966	Defects in ASS1 are the cause of citrullinemia type 1 (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN1 usually manifests in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder CTLN1 form can develop later in childhood or adulthood.
Q76L83	A chromosomal aberration involving ASXL2 is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with MYST3 generates a MYST3-ASXL2 fusion protein.
O60312	Defects in ATP10A are a cause of Angelman syndrome (AS) [MIM:105830]; also known as 'happy puppet syndrome'. AS is characterized by features of severe motor and intellectual retardation, microcephaly, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, hyperactivity, hypopigmentation, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, and an unusual facies characterized by macrostomia, a large mandible and open-mouthed expression, a great propensity for protruding the tongue ('tongue thrusting'), and an occipital groove.
Q9NQ11	Defects in ATP13A2 are the cause of Kufor-Rakeb syndrome (KRS) [MIM:606693]; also known as Parkinson disease-9. KRS is a rare hereditary disease with juvenile onset. In addition to typical signs of Parkinson disease, affected individuals show symptoms of more widespread neurodegeneration, including dementia.
Q4VNC1	A chromosomal aberration involving ATP13A4 is found in 2 patients with specific language impairment (SLI) disorders. Paracentric inversion inv(3)(q25;q29). The inversion produces a disruption of the protein.
P50993	Defects in ATP1A2 are the cause of familial hemiplegic migraine 2 (FHM2) [MIM:602481]. Familial hemiplegic migraine is a rare, severe, autosomal dominant subtype of migraine characterized by aura and some hemiparesis.
P50993	Defects in ATP1A2 are a cause of alternating hemiplegia of childhood (AHC) [MIM:104290]. AHC is typically distinguished from familial hemiplegic migraine by infantile onset of the symptoms and high prevalence of associated neurological deficits that become increasingly obvious with age.
P13637	Defects in ATP1A3 are the cause of dystonia-12 (DYT12) [MIM:128235]; also known as rapid-onset dystonia parkinsonism (RDP). DYT12 is an autosomal dominant form of dystonia- parkinsonism characterized by an unusually rapid evolution of signs and symptoms. Affected persons develop dystonia and parkinsonism between 14 and 45 years of age. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability.
O14983	Defects in ATP2A1 are the cause of Brody disease (BD) [MIM:601003]. BD is an autosomal recessive myopathy characterized by increasing impairment of relaxation of fast twist skeletal muscle during exercise.
P16615	Defects in ATP2A2 are a cause of acrokeratosis verruciformis (AKV) [MIM:101900]; also known as Hopf disease. AKV is a localized disorder of keratinization, which is inherited as an autosomal dominant trait. Its onset is early in life with multiple flat-topped, flesh-colored papules on the hands and feet, punctate keratoses on the palms and soles, with varying degrees of nail involvement. The histopathology shows a distinctive pattern of epidermal features with hyperkeratosis, hypergranulosis, and acanthosis together with papillomatosis. These changes are frequently associated with circumscribed elevations of the epidermis that are said to resemble church spires. There are no features of dyskeratosis or acantholysis, the typical findings in lesions of Darier disease.
P16615	Defects in ATP2A2 are the cause of Darier disease (DD) [MIM:124200]; also known as Darier-White disease (DAR). DD is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic plaques. In a few families, neuropsychiatric abnormalities such as mild mental retardation, schizophrenia, bipolar disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction, and oral contraception exacerbate disease symptoms. Prevalence has been estimated at 1 in 50000.
Q9R0K7	Atp2b2 null deficient mice are deaf.
P98194	Defects in ATP2C1 are the cause of Hailey-Hailey disease (HHD) [MIM:169600]; also known as benign familial pemphigus. HHD is an autosomal dominant disorder characterized by persistent blisters and suprabasal cell separation (acantholysis) of the epidermis, due to impaired keratinocyte adhesion. Patients lacking all isoforms except isoform 2 have HHD.
P32876	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P05496	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P48202	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
A1XQS5	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06645	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P17605	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P07926	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06055	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P56383	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q5RAP9	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06646	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06056	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q3ZC75	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P48201	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P56384	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q5RFL2	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q71S46	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
O43520	Defects in ATP8B1 are the cause of progressive familial intrahepatic cholestasis type 1 (PFIC1) [MIM:211600]; also known as Byler disease. PFIC1 is an autosomal recessive disorder, characterized by early infancy cholestasis, that may be initially episodic but progresses to malnutrition, growth retardation and end-stage liver disease before adulthood.
O43520	Defects in ATP8B1 are the cause of benign recurrent intrahepatic cholestasis type 1 (BRIC1) [MIM:243300]; also known as Summerskill syndrome. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.
O43520	Defects in ATP8B1 can be associated with intrahepatic cholestasis of pregnancy (ICP) [MIM:147480]; also known as pregnancy-related cholestasis. ICP is a multifactorial liver disorder of pregnancy. It presents during the second or, more commonly, the third trimestre of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP causes fetal distress, spontaneous premature delivery and intrauterine death. ICP patients have spontaneous and progressive disappearance of cholestasis after delivery.
Q86WG3	Defects in ATCAY are the cause of cerebellar ataxia, cayman type (ATCAY) [MIM:601238]. ATCAY is found in a population isolate on Grand Cayman Island and causes a marked psychomotor retardation and prominent nonprogressive cerebellar dysfunction including nystagmus, intention tremor, dysarthria, and wide-based ataxic gait. Hypotonia is present from early childhood.
Q8BHE3	Defects in Atcay are the cause of jittery phenotype, which is characterized by severe truncal and limb ataxia and die of starvation and dehydration by 3-4 weeks of age.
Q8WXF7	Defects in SPG3A are the cause of spastic paraplegia autosomal dominant type 3 (SPG3) [MIM:182600]; also known as Strumpell-Lorrain syndrome. Spastic paraplegia is a degenerative spinal cord disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs.
Q13315	Defects in ATM are the cause of ataxia telangiectasia (AT) [MIM:208900]; also known as Louis-Bar syndrome, which includes four complementation groups: A, C, D and E. This rare recessive disorder is characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. AT patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation.
Q13315	Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients.
Q13315	Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL).
Q13315	Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
Q62388	Atm-deficient mice show a phenotype similar to human ataxia telangiectasia (AT) and consistently develop immature T- cells malignancies.
P54259	Defects in ATN1 are the cause of dentatorubral- pallidoluysian atrophy (DRPLA) [MIM:125370]. DRPLA is an autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.
P54259	Defects in ATN1 are the cause of Haw River syndrome (HRS) [MIM:140340]. HRS is a dominant neurodegenerative disease representing a unique spectrum of multiple system degenerations that resemble Huntington disease, spinocerebellar atrophy and dentatorubropallidoluysian atrophy.
P54710	Defects in FXYD2 are the cause of hypomagnesemia type 2 (HOMG2) [MIM:154020]; also known as dominant renal hypomagnesemia or hypomagnesemia with hypocalciuria. HOMG2 is a disorder due to primary renal wasting of magnesium. Plasma levels of other electrolytes are normal. The only abnormality found, in addition to low magnesium levels, is lowered renal excretion of calcium resulting in hypocalciuria.
P18434	Parietal cell autoantigen associated with autoimmune gastritis.
Q8HNQ4	Defects in MT-ATP6 are the cause of neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) [MIM:551500].
Q8HNQ4	Defects in MT-ATP6 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]; also known as Leber optic atrophy. LHON is a maternally inherited disease resulting in acute bilateral blindness due to retinal degeneration predominantly in young men. Cardiac conduction defects and neurological defects have also been described.
Q8HNQ4	Defects in MT-ATP6 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
Q8HNQ4	Defects in MT-ATP6 are a cause of infantile bilateral striatal necrosis [MIM:500003]. Bilateral striatal necrosis is a neurological disorder resembling Leigh syndrome.
Q04656	Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:309400]; also known as kinky hair disease. MNKD is an X- linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes.
Q04656	Defects in ATP7A are the cause of occipital horn syndrome (OHS) [MIM:304150]; also known as X-linked cutis laxa. OHS is an X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities included occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga.
Q64430	Defects in Atp7a are associated with mottled, an X-linked recessive condition characterized by mottled pigmentation of the coat, defects in connective tissue and neonatal or fetal death. It is due to a defect in absorption and transport of copper. The mottled mutants exhibit a diversity of phenotypes. Two of these mutants are called brindled and blotchy and their phenotypes resemble classical Menkes disease (MD) and occipital horn syndrome (OHS) in humans, respectively. Other mutants are called dappled, mosaic, tortoiseshell, pewter, etc.
P35670	Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.
Q64446	Defects in Atp7b are the cause of the toxic milk mouse mutant (tx) phenotype, characterized by accumulation of copper in the liver in a manner similar to that observed in patients with Wilson disease.
Q64535	Deficiency of Atp7b expression is the cause of the Long- Evans Cinnamon (LEC) phenotype, inherited in an autosomal recessive manner, characterized by excessive hepatic copper accumulation, defective holoceruloplasmin biosynthesis, impaired biliary copper excretion and the development of necrotizing hepatitis by 4 months of age.
Q8N5M1	Defects in ATPAF2 are the cause of complex V mitochondrial respiratory chain ATPAF2 subunit deficiency (ATPAF2 deficiency) [MIM:604273]; also called ATP synthase deficiency or ATPase deficiency. ATPAF2 deficiency seems to be an early presenting disease in which lactic acidosis, dysmorphic features, and methyl glutaconic aciduria can be major clues in the diagnosis. Dysmorphic features include a large mouth, prominent nasal bridge, micrognathia, rocker-bottom feet and flexion contractures of the limbs associated with camptodactyly. Patients are hypertonic and have an enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebro spinal fluid (CSF).
Q99J86	Defects in Atrn (isoform 1) are the cause of the autosomal recessive phenotype zitter (zi), which is characterized by progressive hypomyelination and vacuolation in the central nervous system resulting in early-onset tremor and progressive flaccid paresis of the hind limb. This is due to an 8-bp deletion at the splice donor site of intron 12, which results in aberrant and unstable transcripts.
Q9H0Z1	Defects in ATRX are the cause of X-linked alpha- thalassemia/mental retardation syndrome (ATR-X) [MIM:301040]. ATR- X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.
Q9H0Z1	Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:309580]; also called Carpenter-Waziri syndrome (CWS), Juberg- Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.
Q9H0Z1	Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.
Q13535	Defects in ATR are a cause of Seckel syndrome 1 (SCKL1) [MIM:210600]. SCKL1 is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance.
Q9H324	Defects in ADAMTS10 are a cause of the autosomal recessive form of Weill-Marchesani syndrome (WMS) [M