GPR119

Homo sapiens (Human)

GPR119; G-protein coupled receptor 119

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.

Developmental and epileptic encephalopathy 24 (DEE24) [MIM:615871]: A disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals. {ECO:0000269|PubMed:24747641, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Generalized epilepsy with febrile seizures plus 10 (GEFSP10) [MIM:618482]: An autosomal dominant neurologic disorder with incomplete penetrance, characterized by variable types of seizures including absence, tonic-clonic, febrile, focal, and eyelid myoclonia. Some patients have normal neurologic development. Others have mild-to-moderate intellectual disability or autism spectrum disorder. {ECO:0000269|PubMed:29936235, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.

DB05166

Q12797-6

NA

3D-structure; Cell membrane; G-protein coupled receptor; Lipid-binding; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

32134.1

292

0.12

34.96

9.12

8.03

-10.79

THRA

Homo sapiens (Human)

V-erbA-related protein 7; THRA2; THRA1; Nuclear receptor subfamily 1 group A member 1; NR1A1; ERBA1; EAR7; EAR-7; C-erbA-alpha; C-erbA-1

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription.

Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) [MIM:614450]: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance. {ECO:0000269|PubMed:22168587, ECO:0000269|PubMed:24969835, ECO:0000269|PubMed:25670821, ECO:0000269|PubMed:26037512}. The disease is caused by variants affecting the gene represented in this entry.

DB01118; DB00509; DB04855; DB05035; DB03176; DB00451; DB00279; DB01583; DB05235; DB09100

Q9Y2J4; Q9Y2J4-4; O95971; Q8TAP6; Q96JM7; Q15648; Q6FHY5; P31321; Q96A49; O75410-7; Q9JLI4

NA

3D-structure; Alternative splicing; Congenital hypothyroidism; Cytoplasm; Disease variant; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A

29910.1

267

0.07

52.75

5.31

-11.32

-10.73

EPHX2

Homo sapiens (Human)

Bifunctional epoxide hydrolase 2

AB hydrolase superfamily, Epoxide hydrolase family

Ether bond hydrolase

Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid.

Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. {ECO:0000269|PubMed:17332249}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 6 (NS6) [MIM:613224]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. {ECO:0000269|PubMed:19966803}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: RAS-associated autoimmune leukoproliferative disorder (RALD) [MIM:614470]: A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies. {ECO:0000269|PubMed:17517660}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanocytic nevus syndrome, congenital (CMNS) [MIM:137550]: A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip. {ECO:0000269|PubMed:18633438, ECO:0000269|PubMed:23392294}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanosis, neurocutaneous (NCMS) [MIM:249400]: A rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma. {ECO:0000269|PubMed:23392294}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]: Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. {ECO:0000269|PubMed:22499344}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12727991}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB08257; DB08258; DB08259; DB06345; DB12610; DB08256; DB02029; DB04213; DB03677

NA

NA

3D-structure; Acetylation; Alternative splicing; Aromatic hydrocarbons catabolism; Cytoplasm; Detoxification; Direct protein sequencing; Hydrolase; Lipid metabolism; Lipoprotein; Magnesium; Metal-binding; Multifunctional enzyme; Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome

A

61744.9

547

0.09

43.97

5.81

-7.76

-10.61

F2R

Homo sapiens (Human)

NA

TR;PAR1;CF2R

G-protein coupled receptor 1 family

Signaling protein / antagonist

G-protein alpha-subunit binding.G-protein beta-subunit binding.G-protein coupled receptor activity.Receptor binding.Thrombin-activated receptor activity.

3-ketothiolase deficiency (3KTD) [MIM:203750]: An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype. {ECO:0000269|PubMed:1346617, ECO:0000269|PubMed:1715688, ECO:0000269|PubMed:7728148, ECO:0000269|PubMed:9744475}. The disease is caused by variants affecting the gene represented in this entry.

DB05361; DB00086; DB11300; DB09030

Q03135; Q9UNN8

NA

3D-structure; Blood coagulation; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Hemostasis; Membrane; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A

31193.7

282

0.16

36.7

8.2

2.98

-10.59

XDH

Homo sapiens (Human)

Xanthine oxidase; Xanthine dehydrogenase; XDHA

Xanthine dehydrogenase family

CH/CH(2) oxidoreductase

Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). Key enzyme in purine degradation.

Xanthinuria 1 (XAN1) [MIM:278300]: A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol. {ECO:0000269|PubMed:10844591, ECO:0000269|PubMed:11379872, ECO:0000269|PubMed:14551354, ECO:0000269|PubMed:9153281}. The disease is caused by variants affecting the gene represented in this entry.

DB00640; DB00041; DB00437; DB00993; DB00958; DB01136; DB00856; DB00515; DB00746; DB03328; DB00997; DB03516; DB12466; DB04854; DB03147; DB04335; DB01020; DB00583; DB00170; DB01033; DB00157; DB03841; DB00336; DB01250; DB05262; DB06478; DB01168; DB00339; DB00127; DB01685; DB00831

Q9Y3R0-3

NA

2Fe-2S; 3D-structure; Cytoplasm; Disease variant; Disulfide bond; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase; Peroxisome; Proteomics identification; Reference proteome; Secreted

A,B,C,D

143697

1307

0.08

37.9

8.01

7.07

-10.58

GRIN2A

Homo sapiens (Human)

NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A

Glutamate-gated ion channel (TC 1.A.10.1) family, NR1/GRIN1 subfamily

Glutamate-gated ion channel

Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 101 (DEE101) [MIM:619814]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:34611970}. The disease is caused by variants affecting the gene represented in this entry.

DB01931; DB00659; DB06151; DB08838; DB01238; DB00289; DB05824; DB04620; DB03929; DB00647; DB00843; DB00228; DB11823; DB13146; DB06741; DB00142; DB00874; DB08954; DB06738; DB09409; DB09481; DB01043; DB00454; DB00333; DB04896; DB01173; DB00312; DB01174; DB01708; DB00418; DB00193

P05067; P35637; Q12879-1; Q13224; Q62936

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Intellectual disability; Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc

B

53395.6

469

0.11

29.84

8.72

5.65

-10.51

LTA4H

Homo sapiens (Human)

Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase

Peptidase M1 family

Ether bond hydrolase

Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4.

Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR) [MIM:301220]: An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines. {ECO:0000269|PubMed:27019227}. The disease is caused by variants affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication. {ECO:0000269|PubMed:27019227}.; DISEASE: Van Esch-O'Driscoll syndrome (VEODS) [MIM:301030]: An X-linked recessive syndrome characterized by different degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism, and variable congenital malformations. {ECO:0000269|PubMed:31006512}. The disease is caused by variants affecting the gene represented in this entry.

DB07102; DB06917; DB07258; DB07094; DB07259; DB02352; DB07292; DB07104; DB06828; DB08466; DB01197; DB05177; DB03366; DB08040; DB06851; DB02062; DB07099; DB07260; DB07196; DB11781; DB03424; DB07237

Q9BSI4

EC 3.3.2.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Hydrolase; Leukotriene biosynthesis; Lipid metabolism; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Zinc

A

68927

608

0.1

38.84

5.87

-9.86

-10.5

Pseudo LasR

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

Autoinducer-regulated transcriptional regulatory protein family

NA

Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

DB08324

NA

NA

3D-structure; Activator; DNA-binding; Quorum sensing; Reference proteome; Transcription; Transcription regulation

A

18305.5

163

0.12

46.52

5.19

-6.78

-10.49

CYP2D6

Homo sapiens (Human)

P450-DB1; Cytochrome P450-DB1; Cytochrome P450 2D6; CYPIID6; CYP2DL1

Cytochrome P450 family

Paired donor oxygen oxidoreductase

It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes.

A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.

DB01562; DB01472; DB14010; DB12001; DB05812; DB01193; DB00316; DB15568; DB00918; DB06203; DB00866; DB01424; DB01118; DB00321; DB00381; DB00613; DB00543; DB00182; DB00701; DB11785; DB01435; DB01429; DB01274; DB01238; DB14185; DB09204; DB11638; DB06216; DB00637; DB11586; DB00335; DB00289; DB01076; DB00972; DB04957; DB09013; DB16703; DB01086; DB06770; DB01244; DB15982; DB00195; DB01295; DB12236; DB01128; DB04889; DB00810; DB13975; DB08807; DB00188; DB09128; DB12151; DB12752; DB06726; DB00297; DB08808; DB00921; DB01156; DB00490; DB09173; DB00201; DB09061; DB14737; DB06016; DB00521; DB01136; DB00482; DB04846; DB00439; DB00185; DB00608; DB01114; DB00477; DB00356; DB01410; DB01166; DB00501; DB01012; DB00568; DB00604; DB00215; DB12499; DB00283; DB04920; DB14025; DB00349; DB00845; DB01242; DB00575; DB13508; DB00257; DB00363; DB09065; DB05239; DB00907; DB00318; DB11672; DB14635; DB00924; DB00091; DB11963; DB06292; DB04884; DB00496; DB01264; DB09183; DB04840; DB00705; DB06512; DB01151; DB06700; DB16650; DB12161; DB13679; DB09555; DB01191; DB00633; DB01576; DB00514; DB00647; DB11994; DB01551; DB00343; DB01093; DB01075; DB00757; DB01184; DB00843; DB09167; DB00590; DB01142; DB00997; DB00470; DB04855; DB00476; DB00625; DB11979; DB00216; DB15444; DB09039; DB13874; DB01228; DB06735; DB11718; DB00494; DB13757; DB00751; DB00530; DB13443; DB01175; DB06678; DB00187; DB00330; DB01466; DB01628; DB01590; DB12500; DB01023; DB00574; DB06702; DB12265; DB01195; DB04841; DB00472; DB00623; DB01095; DB00176; DB00983; DB02703; DB15149; DB00674; DB05087; DB00317; DB08909; DB00986; DB01218; DB00502; DB00956; DB01611; DB00557; DB09053; DB01177; DB04946; DB00619; DB00458; DB08952; DB00224; DB06370; DB13293; DB04818; DB16200; DB11633; DB06636; DB00951; DB11757; DB00602; DB09570; DB01026; DB00598; DB12212; DB00448; DB11732; DB16217; DB09078; DB00528; DB12070; DB09351; DB01210; DB08918; DB00281; DB04948; DB01206; DB00836; DB01601; DB00455; DB04871; DB09195; DB06708; DB04829; DB09238; DB00934; DB14921; DB00737; DB14009; DB09224; DB00170; DB00454; DB00532; DB13530; DB06691; DB01071; DB00933; DB01577; DB00333; DB00763; DB01403; DB01028; DB09241; DB01214; DB01233; DB00264; DB00379; DB06148; DB01388; DB01110; DB00211; DB01454; DB06595; DB00834; DB00805; DB08893; DB00370; DB12523; DB01171; DB00745; DB14011; DB09049; DB00731; DB04861; DB01149; DB00220; DB09048; DB00238; DB00627; DB00622; DB00699; DB02701; DB00184; DB01115; DB04868; DB12005; DB00540; DB00334; DB14881; DB00338; DB00904; DB11130; DB04911; DB01173; DB11837; DB04938; DB01096; DB01580; DB01062; DB00497; DB06412; DB01192; DB01267; DB00377; DB06603; DB00715; DB06589; DB00022; DB01359; DB00738; DB01074; DB08922; DB00850; DB03783; DB00780; DB00914; DB00252; DB05316; DB01100; DB00960; DB00592; DB01621; DB04951; DB17472; DB11642; DB08901; DB01297; DB15822; DB01087; DB01035; DB00433; DB00396; DB01131; DB00420; DB01069; DB09288; DB01182; DB00571; DB04216; DB01224; DB00908; DB00468; DB01129; DB00863; DB00243; DB00234; DB14761; DB00409; DB06506; DB02709; DB11855; DB13174; DB11753; DB08864; DB14840; DB00734; DB12693; DB00503; DB00953; DB09291; DB15119; DB00412; DB05271; DB12332; DB11614; DB06654; DB01232; DB01037; DB06144; DB01104; DB00203; DB00641; DB01591; DB00398; DB12713; DB00489; DB06727; DB01323; DB09118; DB06820; DB06729; DB06608; DB11770; DB00675; DB00706; DB06204; DB06083; DB01079; DB12095; DB06287; DB00857; DB00342; DB13775; DB04905; DB04844; DB11712; DB00277; DB00679; DB01623; DB00208; DB00373; DB01409; DB00932; DB06137; DB01036; DB05109; DB00193; DB00752; DB00656; DB12245; DB00726; DB00792; DB00209; DB15328; DB09076; DB13609; DB15091; DB11915; DB00862; DB08881; DB00285; DB00661; DB06217; DB06684; DB09185; DB00570; DB00361; DB11739; DB09068; DB01392; DB00549; DB15688; DB00425; DB01624

NA

EC 1.14.14.-

3D-structure; Alternative splicing; Cholesterol metabolism; Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism

A

51898.1

464

0.09

43.83

6.76

-0.99

-10.49

MAOB

Homo sapiens (Human)

MAO-B; Amine oxidase [flavin-containing] B

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.

Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.

DB08176; DB02211; DB08516; DB08480; DB01472; DB04307; DB07512; DB07513; DB00915; DB00182; DB06698; DB04889; DB00215; DB09130; DB04147; DB00988; DB01363; DB00668; DB01175; DB02509; DB03147; DB14914; DB00614; DB04818; DB02095; DB01247; DB00601; DB01577; DB01442; DB01171; DB08082; DB02643; DB04677; DB03894; DB08804; DB04820; DB00184; DB04821; DB12612; DB01626; DB00780; DB00191; DB00388; DB01132; DB00721; DB01168; DB01367; DB09363; DB06654; DB01037; DB01104; DB14569; DB09042; DB00752; DB16446; DB09185; DB04832; DB00909

P55212; P28329-3; Q8NI60; Q5RI15; Q92915-2; P22607; Q53GS7; P06396; P01112; O14901; P13473-2; P21397; Q9BVL2; O75400-2; P62826; Q6NTF9-3; Q9Y371; Q7Z699; Q9UMX0; Q9Y649

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; FAD; Flavoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane; Oxidoreductase; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A,B

56019.9

494

0.09

34.81

6.51

-2.2

-10.46

TPMT

Homo sapiens (Human)

NA

NA

Class I-like SAM-binding methyltransferase superfamily, TPMT family

Transferase

Thiopurine S-methyltransferase activity.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB00993; DB00436; DB01327; DB01033; DB01250; DB01021

Q8TAP4-4; Q15047-2; P61981

2.1.1.67

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Methyltransferase; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A

25971.5

229

0.12

32.58

6.74

-0.6

-10.46

PFF0160c

Plasmodium falciparum (isolate 3D7)

NA

NA

Dihydroorotate dehydrogenase family, Type 2 subfamily

Oxidoreductase

Dihydroorotate dehydrogenase activity.

Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. The disease is caused by variants affecting the gene represented in this entry.

DB01117

NA

1.3.5.2

3D-structure; Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Pyrimidine biosynthesis; Reference proteome; Transit peptide; Transmembrane; Transmembrane helix

A,B

42573.5

378

0.1

36.63

8.21

3.17

-10.44

MAP3K2

Homo sapiens (Human)

NA

MEKK2;MAPKKK2

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily

Transferase

ATP binding.MAP kinase kinase kinase activity.Metal ion binding.Protein kinase activity.Protein kinase binding.Protein serine/threonine kinase activity.

Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. The disease is caused by variants affecting the gene represented in this entry.

DB06616; DB12010

Q13163; P31947; Q9H7B4-1; Q9UNE7; P62258

2.7.11.25

3D-structure; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

I,J

48735.2

425

0.08

44.28

7.24

0.6

-10.44

PROC

Homo sapiens (Human)

Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; PROC; Blood coagulation factor XIV; Autoprothrombin IIA; Anticoagulant protein C; Activation peptide

Peptidase S1 family

Peptidase

Protein C is avitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.

Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency. {ECO:0000269|PubMed:1301959, ECO:0000269|PubMed:1347706, ECO:0000269|PubMed:1511989, ECO:0000269|PubMed:1868249, ECO:0000269|PubMed:2437584, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:25748729, ECO:0000269|PubMed:2602169, ECO:0000269|PubMed:7792728, ECO:0000269|PubMed:7865674, ECO:0000269|PubMed:8292730, ECO:0000269|PubMed:8398832, ECO:0000269|PubMed:8499568, ECO:0000269|PubMed:8560401, ECO:0000269|PubMed:8829639, ECO:0000269|PubMed:9798967}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. {ECO:0000269|PubMed:1511988, ECO:0000269|PubMed:1593215, ECO:0000269|PubMed:1611081, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:7841323, ECO:0000269|PubMed:7841324, ECO:0000269|PubMed:7878626}. The disease is caused by variants affecting the gene represented in this entry.

DB13192; DB00025; DB09131; DB09332; DB13998; DB00170; DB13999; DB13149; DB00464; DB14738

A8MQ03; P51511

EC 3.4.21.69

3D-structure; Alternative splicing; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Endoplasmic reticulum; Gamma-carboxyglutamic acid; Glycoprotein; Golgi apparatus; Hemostasis; Hydrolase; Hydroxylation; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Thrombophilia; Zymogen

C,D

45326

411

0.12

40.68

7.07

0.29

-10.4

soxA

Bacillus sp. (strain B-0618)

NA

sox

MSOX/MTOX family, MSOX subfamily

Oxidoreductase

Sarcosine oxidase activity.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB03098; DB01918; DB03517; DB03147; DB03366; DB02083; DB02543

NA

1.5.3.1

3D-structure; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; Oxidoreductase

A,B

42606.4

385

0.1

26.97

5.27

-17.18

-10.4

KDM1B

Homo sapiens (Human)

Lysine-specific histone demethylase 2; LSD2; Flavin-containing amine oxidase domain-containing protein 1; C6orf193; AOF1

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor.

Angioedema, hereditary, 1 (HAE1) [MIM:106100]: An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional. {ECO:0000269|PubMed:12773530, ECO:0000269|PubMed:1363816, ECO:0000269|PubMed:1451784, ECO:0000269|PubMed:14635117, ECO:0000269|PubMed:16409206, ECO:0000269|PubMed:2118657, ECO:0000269|PubMed:2296585, ECO:0000269|PubMed:22994404, ECO:0000269|PubMed:2365061, ECO:0000269|PubMed:24456027, ECO:0000269|PubMed:3178731, ECO:0000269|PubMed:7814636, ECO:0000269|PubMed:7883978, ECO:0000269|PubMed:8172583, ECO:0000269|PubMed:8529136, ECO:0000269|PubMed:8755917, ECO:0000269|Ref.41}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q96L03

EC 1.-.-.-

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Developmental protein; FAD; Flavoprotein; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger

A,C

85795.5

763

0.1

37.87

8.41

9.16

-10.41

DHODH

Homo sapiens (Human)

Dihydroorotate oxidase; Dihydroorotate dehydrogenase (quinone), mitochondrial; DHOdehase; DHODH

Dihydroorotate dehydrogenase family, Type 2 subfamily

CH-CH donor oxidoreductase

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. {ECO:0000269|PubMed:19915526}. The disease is caused by variants affecting the gene represented in this entry.

DB07559; DB07561; DB08172; DB08169; DB07443; DB07978; DB07975; DB04281; DB08249; DB07977; DB07976; DB04583; DB08008; DB01117; DB03523; DB03480; DB02613; DB04147; DB03247; DB01097; DB06481; DB08006; DB02262; DB05125; DB08880; DB07646

Q6ZMZ0; P49638

EC 1.3.5.2

3D-structure; Disease variant; Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Proteomics identification; Pyrimidine biosynthesis; Reference proteome; Transit peptide; Transmembrane; Transmembrane helix

A

38341.4

353

0.05

39.27

9.28

5.52

-10.4

mmaA2

Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

NA

Rv0644c;mma2

CFA/CMAS family

Transferase

Cyclopropane-fatty-acyl-phospholipid synthase activity.Methyltransferase activity.

Oocyte/zygote/embryo maturation arrest 16 (OZEMA16) [MIM:617234]: A rare cause of female primary infertility. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27545678}. The disease is caused by variants affecting the gene represented in this entry.

DB01718; DB01752

NA

2.1.1.79

3D-structure; Acetylation; Lipid biosynthesis; Lipid metabolism; Methyltransferase; Reference proteome; S-adenosyl-L-methionine; Transferase

A

32493.6

285

0.1

43.61

5.53

-10.17

-10.39

DPP8

Homo sapiens (Human)

Prolyl dipeptidase DPP8; MSTP141; MSTP135; MSTP097; Dipeptidyl peptidase VIII; Dipeptidyl peptidase IV-related protein 1; DPRP1; DPRP-1; DPP VIII; DP8

Peptidase S9B family, DPPIV subfamily

Peptidase

Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.14.5

3D-structure; Alternative splicing; Aminopeptidase; Apoptosis; Cytoplasm; Hydrolase; Protease; Proteomics identification; Reference proteome; Serine protease

A,D

97764.9

849

0.12

47.71

5.69

-21.66

-10.39

CYP46A1

Homo sapiens (Human)

Cytochrome P450 46A1; CYP46; Cholesterol 24S-hydroxylase; Cholesterol 24-monooxygenase; CH24H

Cytochrome P450 family

Paired donor oxygen oxidoreductase

Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation. By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning. Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis. Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain. May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole. P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain.

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1) [MIM:607250]: A form of spinocerebellar ataxia, 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. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence. {ECO:0000269|PubMed:12244316, ECO:0000269|PubMed:15647511, ECO:0000269|PubMed:15920477, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:17948061}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.14.14.25

3D-structure; Alternative splicing; Cell projection; Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism; Synapse; Transmembrane; Transmembrane helix

A

48977

427

0.1

49.59

9.04

6.25

-10.39