NR3C1

Homo sapiens (Human)

Nuclear receptor subfamily 3 group C member 1; GRL; GR

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity).

Glucocorticoid resistance, generalized (GCCR) [MIM:615962]: An autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of Cushing syndrome typical signs. Clinical features include hypoglycemia, hypertension, metabolic alkalosis, chronic fatigue and profound anxiety. {ECO:0000269|PubMed:11589680, ECO:0000269|PubMed:11701741, ECO:0000269|PubMed:12050230, ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:1704018, ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:20335448, ECO:0000269|PubMed:21362280, ECO:0000269|PubMed:23426617, ECO:0000269|PubMed:24483153, ECO:0000269|PubMed:26031419, ECO:0000269|PubMed:26541474, ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:7683692}. The disease is caused by variants affecting the gene represented in this entry.

DB00240; DB04630; DB00288; DB00394; DB00443; DB14669; DB01222; DB01410; DB01013; DB13158; DB00838; DB01380; DB13003; DB11921; DB01260; DB00547; DB01234; DB14649; DB00223; DB09095; DB06781; DB01395; DB00687; DB00663; DB00180; DB00591; DB01047; DB00324; DB01185; DB00846; DB13867; DB08906; DB00588; DB11619; DB02210; DB00769; DB00741; DB14538; DB14539; DB14540; DB14541; DB14542; DB14543; DB14544; DB00367; DB14596; DB00253; DB00351; DB00959; DB00834; DB00764; DB14512; DB00717; DB12637; DB05423; DB01384; DB01130; DB00860; DB15566; DB14631; DB00635; DB00396; DB00896; DB14583; DB00421; DB09091; DB00620; DB08867; DB00596; DB15114

P31749; P01730; P00533; P41235; P07900; Q6ZU52; P06239; P28702; Q14141; O95416; P82094; P59598; Q62667; Q61026

NA

3D-structure; Acetylation; Alternative initiation; Alternative splicing; Apoptosis; Cell cycle; Cell division; Chromatin regulator; Chromosome; Chromosome partition; Cytoplasm; Cytoskeleton; Disease variant; DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; Methylation; Mitochondrion; Mitosis; Nucleus; Phosphoprotein; Proteomics identification; Pseudohermaphroditism; Receptor; Reference proteome; RNA-binding; Steroid-binding; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

30565.2

262

0.1

46.97

5.79

-4.17

-10.12

BRAF

Homo sapiens (Human)

V-Raf murine sarcoma viral oncogene homolog B1; RAFB1; Proto-oncogene B-Raf; P94; BRAF1; BRAF(V599E); BRAF serine/threonine kinase; B-raf protein; B-Raf

Protein kinase superfamily, TKL Ser/Thr protein kinase family, RAF subfamily

Kinase

May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway. Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.

Defects in BRAF are found in a wide range of cancers. {ECO:0000269|PubMed:18974108}.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12198537, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:23263490, ECO:0000269|PubMed:24455489}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. {ECO:0000269|PubMed:12460919}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. {ECO:0000269|PubMed:14612909}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Cardiofaciocutaneous syndrome 1 (CFC1) [MIM:115150]: A multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 7 (NS7) [MIM:613706]: 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:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: LEOPARD syndrome 3 (LPRD3) [MIM:613707]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation. {ECO:0000269|PubMed:18974108}.

DB08553; DB08912; DB11718; DB12010; DB07000; DB06999; DB05984; DB08896; DB14840; DB00398; DB08881; DB05190

P15056; P01112; P08238; P46940; Q02750; P36507; Q13233; P01111; Q02156; P04049; Q15349; P31947; Q13114; P31946; P62258; P63104; Q61097; P29678; Q99N57; Q8CGE9

EC 2.7.11.1

3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Cardiomyopathy; Cell membrane; Chromosomal rearrangement; Cytoplasm; Deafness; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Isopeptide bond; Kinase; Membrane; Metal-binding; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation; Zinc; Zinc-finger

A,B

28819.9

252

0.08

46.62

9.15

6.46

-10.12

GRM5

Homo sapiens (Human)

MGLUR5; GPRC1E

G-protein coupled receptor 3 family

GPCR glutamate

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Charcot-Marie-Tooth disease, axonal, 2D (CMT2D) [MIM:601472]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:17101916, ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:20169446, ECO:0000269|PubMed:24604904, ECO:0000269|PubMed:25168514, ECO:0000269|PubMed:26244500, ECO:0000269|PubMed:26503042, ECO:0000269|PubMed:31173493}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 5 (HMND5) [MIM:600794]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:23279345, ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:26503042}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy, infantile, James type (SMAJI) [MIM:619042]: An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency. {ECO:0000269|PubMed:32181591}. The disease is caused by variants affecting the gene represented in this entry.

DB00659; DB05070; DB12733; DB06201

P41594; Q7Z6G3

NA

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

A

27065.4

247

0.13

42.92

9.24

11.34

-10.12

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

-10.12

CYP1A2

Homo sapiens (Human)

NA

NA

Cytochrome P450 family

Oxidoreductase

Aromatase activity.Caffeine oxidase activity.Demethylase activity.Electron carrier activity.Enzyme binding.Heme binding.Iron ion binding.Monooxygenase activity.Oxidoreductase activity.Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen.Oxygen binding.

Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. The disease is caused by variants affecting the gene represented in this entry.

DB08496; DB01667; DB14132; DB04356; DB02489; DB11932; DB12001; DB05812; DB13573; DB01418; DB00316; DB15568; DB06594; DB00518; DB05396; DB00969; DB07453; DB01424; DB01223; DB01118; DB00321; DB00261; DB01217; DB01435; DB06605; DB05676; DB06413; DB06216; DB01072; DB15011; DB06442; DB06626; DB00993; DB00972; DB13203; DB05015; DB16703; DB06769; DB01086; DB06770; DB06771; DB06732; DB00195; DB04889; DB11967; DB13975; DB00188; DB12151; DB01558; DB14018; DB13812; DB00201; DB09061; DB14737; DB11791; DB06774; DB00564; DB06016; DB01136; DB12814; DB00477; DB00356; DB01166; DB00501; DB01012; DB00568; DB00827; DB00537; DB00215; DB12499; DB14025; DB00349; DB01242; DB00575; DB00758; DB00363; DB00286; DB11672; DB14635; DB00924; DB08912; DB00851; DB06292; DB01254; DB01609; DB01151; DB16650; DB12161; DB01191; DB00633; DB11994; DB00586; DB11511; DB12945; DB00280; DB01184; DB09167; DB05928; DB01142; DB09273; DB00470; DB00476; DB00625; DB15444; DB06210; DB13874; DB11718; DB00467; DB11404; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00655; DB04574; DB13592; DB00330; DB00898; DB00977; DB00773; DB01628; DB00927; DB04854; DB01482; DB00574; DB12265; DB15669; DB01195; DB08972; DB04841; DB00544; DB00472; DB00499; DB00176; DB01320; DB00998; DB14029; DB06160; DB01044; DB01241; DB01155; DB01645; DB01381; DB00986; DB00365; DB00400; DB05708; DB00629; DB00502; DB01094; DB14999; DB04076; DB11737; DB00619; DB00458; DB11564; DB01306; DB09456; DB09564; DB01307; DB00047; DB01309; DB00030; DB00046; DB11567; DB00071; DB11568; DB05258; DB00034; DB00105; DB15131; DB00011; DB00018; DB00069; DB00060; DB00068; DB00033; DB00951; DB11757; DB09570; DB01026; DB01097; DB16217; DB09078; DB01002; DB05667; DB00281; DB12406; DB09198; DB04948; DB00978; DB06448; DB16220; DB01601; DB00455; DB04871; DB06077; DB01283; DB00772; DB00934; DB06234; DB14009; DB00784; DB01065; DB00170; DB00454; DB00532; DB00333; DB00763; DB00553; DB01028; DB09241; DB01233; DB00379; DB06148; DB01388; DB06595; DB00370; DB16236; DB00745; DB11763; DB00218; DB06510; DB14011; DB00461; DB00607; DB00779; DB00788; DB06600; DB00238; DB06803; DB00184; DB01115; DB11793; DB00435; DB05115; DB00717; DB01059; DB00540; DB05990; DB01165; DB00334; DB16267; DB00338; DB00904; DB11632; DB11443; DB01173; DB11837; DB09330; DB01303; DB11697; DB00377; DB00715; DB06589; DB11774; DB00487; DB00008; DB00022; DB09122; DB13634; DB00806; DB11198; DB08883; DB00850; DB03783; DB01174; DB00388; DB00252; DB11450; DB01100; DB13823; DB04951; DB17472; DB11642; DB08910; DB15822; DB01058; DB01087; DB00794; DB00420; DB09288; DB01182; DB06479; DB00818; DB00571; DB13449; DB11892; DB04216; DB00908; DB00468; DB01129; DB00980; DB09290; DB00863; DB01367; DB00409; DB02709; DB13174; DB01045; DB11753; DB00740; DB14924; DB00503; DB00533; DB01656; DB15119; DB00268; DB00296; DB00412; DB00817; DB12332; DB13772; DB06654; DB11491; DB00418; DB01037; DB11689; DB06290; DB13261; DB15093; DB00052; DB00398; DB01208; DB09118; DB00428; DB06820; DB00382; DB00675; DB06083; DB09071; DB05488; DB09256; DB01079; DB01405; DB00857; DB08880; DB11712; DB01412; DB00277; DB00730; DB01623; DB00208; DB06137; DB00697; DB01056; DB06264; DB00752; DB00384; DB12245; DB00831; DB15442; DB00440; DB00685; DB08867; DB14989; DB13609; DB06235; DB00313; DB08881; DB00661; DB09185; DB12026; DB00682; DB02134; DB00549; DB00744; DB00315; DB00425; DB09225; DB09120

O95870

1.14.14.1; 4.2.1.152

3D-structure; Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism

A

54475

480

0.1

40.43

9.16

9.89

-10.11

NR3C2

Homo sapiens (Human)

Nuclear receptor subfamily 3 group C member 2; Mineralocorticoid receptor; MLR; MCR; Inner ear mineralocorticoid receptor; Delta

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol.

Pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735]: A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. {ECO:0000269|PubMed:11134129, ECO:0000269|PubMed:12788847, ECO:0000269|PubMed:16954160, ECO:0000269|PubMed:16972228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115]: Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion. {ECO:0000269|PubMed:10884226, ECO:0000269|PubMed:15908963, ECO:0000269|PubMed:15967794}. The disease is caused by variants affecting the gene represented in this entry.

DB04630; DB01013; DB04652; DB06780; DB01134; DB01395; DB00700; DB01023; DB16165; DB00687; DB13867; DB08906; DB00588; DB02998; DB00393; DB00396; DB00421; DB02901; DB13951; DB00624; DB13943; DB13944; DB15114

NA

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Endoplasmic reticulum; Lipid-binding; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Zinc; Zinc-finger

A

29012.4

249

0.12

51.27

6.3

-2.08

-10.1

cyp51

Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

NA

MTCY369.09c;Rv0764c

Cytochrome P450 family

NA

Sterol 14alpha-demethylase whose physiological substrate is not known. Accepts electrons from the iron-sulfur ferredoxin Fdx encoded by an adjacent gene (PubMed:10430874, PubMed:16819841). In vitro, catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol, to produce the 8,14-dienes stereoselectively (PubMed:10430874). {ECO:0000269|PubMed:10430874, ECO:0000269|PubMed:16819841}."

Thrombocytopenia 4 (THC4) [MIM:612004]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:18345000}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

1.14.15.36

3D-structure; Cytoplasm; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism

A

49740

440

0.09

36.42

5.61

-13.63

-10.1

AR

Homo sapiens (Human)

Testosterone receptor; Nuclear receptor subfamily 3 group C member 4; NR3C4; Dihydrotestosterone receptor; DHTR

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.

Androgen insensitivity syndrome (AIS) [MIM:300068]: An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10221770, ECO:0000269|PubMed:10404311, ECO:0000269|PubMed:10458483, ECO:0000269|PubMed:10571951, ECO:0000269|PubMed:10590024, ECO:0000269|PubMed:10690872, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:11744994, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1426313, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:1464650, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:1480178, ECO:0000269|PubMed:1487249, ECO:0000269|PubMed:1569163, ECO:0000269|PubMed:1609793, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:16595706, ECO:0000269|PubMed:1775137, ECO:0000269|PubMed:1999491, ECO:0000269|PubMed:2082179, ECO:0000269|PubMed:2594783, ECO:0000269|PubMed:7537149, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7633398, ECO:0000269|PubMed:7641413, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7962294, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:7981689, ECO:0000269|PubMed:7993455, ECO:0000269|PubMed:8040309, ECO:0000269|PubMed:8096390, ECO:0000269|PubMed:8103398, ECO:0000269|PubMed:8162033, ECO:0000269|PubMed:8224266, ECO:0000269|PubMed:8281140, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8339746, ECO:0000269|PubMed:8413310, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8626869, ECO:0000269|PubMed:8647313, ECO:0000269|PubMed:8683794, ECO:0000269|PubMed:8723113, ECO:0000269|PubMed:8768864, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8830623, ECO:0000269|PubMed:8918984, ECO:0000269|PubMed:8990010, ECO:0000269|PubMed:9001799, ECO:0000269|PubMed:9007482, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9106550, ECO:0000269|PubMed:9160185, ECO:0000269|PubMed:9252933, ECO:0000269|PubMed:9255042, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9328206, ECO:0000269|PubMed:9544375, ECO:0000269|PubMed:9554754, ECO:0000269|PubMed:9610419, ECO:0000269|PubMed:9627582, ECO:0000269|PubMed:9698822, ECO:0000269|PubMed:9851768, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.116, ECO:0000269|Ref.182}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal and bulbar muscular atrophy X-linked 1 (SMAX1) [MIM:313200]: An X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. {ECO:0000269|PubMed:15851746}. The disease is caused by variants affecting the gene represented in this entry. Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.; DISEASE: Prostate cancer, hereditary, X-linked 3 (HPCX3) [MIM:301120]: A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:8530589}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:10363963, ECO:0000269|PubMed:10569618, ECO:0000269|PubMed:1562539, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:17311914, ECO:0000269|PubMed:2260966, ECO:0000269|PubMed:25091737, ECO:0000269|PubMed:8187068, ECO:0000269|PubMed:8274409, ECO:0000269|PubMed:8827083}.; DISEASE: Androgen insensitivity, partial (PAIS) [MIM:312300]: A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10470409, ECO:0000269|PubMed:10502786, ECO:0000269|PubMed:10543676, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:1303262, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1424203, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:2010552, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7649358, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7909256, ECO:0000269|PubMed:7910529, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:8033918, ECO:0000269|PubMed:8097257, ECO:0000269|PubMed:8126121, ECO:0000269|PubMed:8205256, ECO:0000269|PubMed:8281139, ECO:0000269|PubMed:8325932, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8550758, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8823308, ECO:0000269|PubMed:8824883, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9196614, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9329414, ECO:0000269|PubMed:9543136, ECO:0000269|PubMed:9607727, ECO:0000269|PubMed:9768671, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.124}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypospadias 1, X-linked (HYSP1) [MIM:300633]: A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome. {ECO:0000269|PubMed:8097257}. The disease is caused by variants affecting the gene represented in this entry.

DB07422; DB07039; DB04709; DB07717; DB07454; DB02932; DB08035; DB01481; DB08088; DB08461; DB08087; DB07421; DB01063; DB07423; DB11901; DB01128; DB07286; DB01541; DB14639; DB01564; DB12499; DB04839; DB01406; DB12941; DB09123; DB00255; DB06133; DB01395; DB00858; DB15488; DB11219; DB08899; DB13155; DB00655; DB09086; DB02266; DB01185; DB00623; DB00499; DB11619; DB11064; DB01026; DB15647; DB00367; DB08089; DB05234; DB13934; DB11425; DB06710; DB02998; DB11429; DB00648; DB08804; DB00984; DB00665; DB06713; DB00717; DB09371; DB00957; DB09389; DB00621; DB01428; DB06412; DB01608; DB11447; DB01708; DB00396; DB07419; DB07769; DB14583; DB00421; DB02901; DB13951; DB06718; DB00675; DB00624; DB13943; DB13944; DB01420; DB13946; DB06870; DB08604; DB08867

P00519; Q9UBL3; P51451; Q8WV28; O60885-1; P78543; Q14790; P24385; Q92793; O14595; P35222; Q9UER7; P20711; P11308; P07332; P09769; Q02790; P55317; O75593; Q14451; P06396; P56524; Q16665; Q16666; O15357; Q15652; O95251; Q9BY66; Q9BY66-3; Q03164; O14686; P06239; P07948; P20794; P42679; Q00987; Q15596; Q14686; O96028; Q99497; P27986; O00459; Q92569; P19174; P16885; Q06830; P78527; Q06124; P20936; Q9UBS8; Q9Y252; O14796; Q9NP31; P29353; Q6S5L8; Q5VZ18; Q15797; O14544; P12931; Q9ULZ2; P63165; Q9HBL0; P07947; Q9R1E0; Q06986

NA

3D-structure; Activator; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein; Metal-binding; Neurodegeneration; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Pseudohermaphroditism; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Triplet repeat expansion; Ubl conjugation; Zinc; Zinc-finger

A

29137.9

250

0.11

42.11

8.94

5.43

-10.11

CHRNA4

Homo sapiens (Human)

Nicotinic acetylcholine receptor alpha4; CHRNA4; Alpha-4 nAChR

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-4/CHRNA4 sub-subfamily

Neurotransmitter receptor

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasmamembrane permeable to sodium ions.

Epilepsy, nocturnal frontal lobe, 1 (ENFL1) [MIM:600513]: An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. {ECO:0000269|PubMed:10563623, ECO:0000269|PubMed:14623738, ECO:0000269|PubMed:7550350}. The disease is caused by variants affecting the gene represented in this entry.

DB00915; DB01351; DB01352; DB00572; DB01483; DB00237; DB00241; DB01353; DB00564; DB00565; DB09028; DB01245; DB00514; DB01496; DB07720; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00898; DB01354; DB01355; DB00753; DB00657; DB00333; DB00463; DB00849; DB00184; DB00312; DB01174; DB00981; DB05458; DB00794; DB05740; DB00747; DB00418; DB00202; DB00306; DB00599; DB01273

Q6UY14-3; P05067; P83916; Q6UXH1-1; Q6UXH1-3; P20042; Q9NZR2; Q92673; P17787

NA

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport

A,B

84601.2

728

0.13

39.72

5.86

-9.84

-10.11

CHRNB2

Homo sapiens (Human)

Nicotinic acetylcholine receptor beta2; Nicotinic acetylcholine receptor beta 2-subunit protein; CHRNB2; Beta-2 nAChR; Alpha-4/beta-2 nicotinic receptor

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Beta-2/CHRNB2 sub-subfamily

Neurotransmitter receptor

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions.

Epilepsy, nocturnal frontal lobe, 3 (ENFL3) [MIM:605375]: An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. {ECO:0000269|PubMed:11062464, ECO:0000269|PubMed:11104662}. The disease is caused by variants affecting the gene represented in this entry.

DB00572; DB00237; DB00565; DB09028; DB01245; DB00514; DB07720; DB00898; DB00753; DB00657; DB00333; DB00184; DB00981; DB05458; DB05855; DB05740; DB00747; DB00202; DB01273

P43681-1; P30532

NA

3D-structure; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport

A,B

84601.2

728

0.13

39.72

5.86

-9.84

-10.11

HBV C

Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979) (HBV-D)

Core antigen; Core protein; HBcAg; p21.5

Orthohepadnavirus core antigen family

NA

Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions.

Oocyte/zygote/embryo maturation arrest 14 (OZEMA14) [MIM:620276]: An autosomal recessive female infertility disorder characterized by oocyte maturation arrest, fertilization failure, and/or early embryonic arrest. {ECO:0000269|PubMed:32666501, ECO:0000269|PubMed:33683667, ECO:0000269|PubMed:33898437, ECO:0000269|PubMed:34218387}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Alternative initiation; Capsid protein; Cytoplasmic inwards viral transport; DNA-binding; Host cytoplasm; Host-virus interaction; Microtubular inwards viral transport; Phosphoprotein; Reference proteome; Repeat; RNA-binding; T=4 icosahedral capsid protein; Viral penetration into host nucleus; Virion; Virus entry into host cell

A,B

32388.9

286

0.12

42.05

5.06

-11.81

-10.1

NPY1R

Homo sapiens (Human)

Neuropeptide Y-Y1 receptor; Neuropeptide Y receptor Y1; Neuropeptide Y Y(1) receptor; NPY1R; NPY1-R

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid.

3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911]: A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:11479731, ECO:0000269|PubMed:12647205, ECO:0000269|PubMed:16601895, ECO:0000269|PubMed:23751782, ECO:0000269|PubMed:25511235, ECO:0000269|PubMed:29597274}. The disease is caused by variants affecting the gene represented in this entry.

DB05004

P10082

NA

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

A

53153.7

463

0.13

34

8.93

9.46

-10.11

acrB

Escherichia coli (strain K12)

NA

b0462;acrE;JW0451

Resistance-nodulation-cell division (RND) (TC 2.A.6) family

Transport protein

Drug:proton antiporter activity.Drug transmembrane transporter activity.Identical protein binding.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB03619; DB04209; DB03825

P31224; P0AAW9; P0ADZ7

NA

3D-structure; Cell inner membrane; Cell membrane; Membrane; Reference proteome; Transmembrane; Transmembrane helix; Transport

A,B,C

60242.4

553

0.08

29.1

4.76

-18.86

-10.1

SULT1E1

Homo sapiens (Human)

NA

STE

Sulfotransferase 1 family

Transferase

Aryl sulfotransferase activity.Estrone sulfotransferase activity.Flavonol 3-sulfotransferase activity.Steroid binding.Steroid sulfotransferase activity.Sulfotransferase activity.

Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN) [MIM:137200]: An autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves. {ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:22961002, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:31088288}. The disease is caused by variants affecting the gene represented in this entry.

DB02902; DB03346; DB01812; DB00714; DB14635; DB01176; DB00977; DB09288; DB00675; DB09100

O76083; O76083-2

2.8.2.4

3D-structure; Cytoplasm; Lipid metabolism; Lipid-binding; Proteomics identification; Reference proteome; Steroid-binding; Transferase

A,B

34022.7

285

0.15

32.76

6.33

-2.75

-10.09

WNK3

Homo sapiens (Human)

Serine/threonine-protein kinase WNK3; Protein kinase with no lysine 3; Protein kinase lysine-deficient 3; KIAA1566

Protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily

NA

Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.

Prieto syndrome (PRS) [MIM:309610]: An X-linked recessive disorder characterized by impaired intellectual development, developmental delay, autism spectrum disorder, variable epilepsy, craniofacial dysmorphism, and structural brain abnormalities including polymicrogyria and cerebral atrophy. {ECO:0000269|PubMed:35678782}. The disease is caused by variants affecting the gene represented in this entry.

NA

P42574; P52954; Q04864-2

EC 2.7.11.1

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Intellectual disability; Kinase; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

30818.4

269

0.1

41.03

6.27

-2.07

-10.09

IRAK4

Homo sapiens (Human)

Interleukin-1 receptor-associated kinase 4; IRAK-4

Protein kinase superfamily, TKL Ser/Thr protein kinase family, Pelle subfamily

Kinase

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.

Immunodeficiency 67 (IMD67) [MIM:607676]: An autosomal recessive primary immunodeficiency characterized by recurrent, life-threatening systemic and invasive bacterial infections beginning in infancy or early childhood. {ECO:0000269|PubMed:12637671, ECO:0000269|PubMed:12925671, ECO:0000269|PubMed:16950813, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:19663824, ECO:0000269|PubMed:21057262, ECO:0000269|PubMed:24316379}. The disease is caused by variants affecting the gene represented in this entry.

DB08590; DB12010

Q9UBH0; O43187; Q99836; Q99836-1; Q96FA3; Q9HAT8; P58753; Q9C029; P0DPA2; Q96LX8; Q8K4B2

EC 2.7.11.1

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Immunity; Innate immunity; Kinase; Magnesium; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

A

30948.8

276

0.08

43.33

5.09

-13.45

-10.1

ENPP2

Homo sapiens (Human)

LysoPLD; Ectonucleotide pyrophosphatase/phosphodiesterase family member 2; E-NPP 2; Autotaxin; ATX

Nucleotide pyrophosphatase/phosphodiesterase family

Phosphoric diester hydrolase

Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor.

Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:30988594, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. The disease is caused by variants affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.

NA

NA

EC 3.1.4.39

3D-structure; Alternative splicing; Calcium; Chemotaxis; Cleavage on pair of basic residues; Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Obesity; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Zinc

A

85397.4

740

0.12

58.63

7.16

1.02

-10.1

HRAS

Homo sapiens (Human)

p21ras; cHras; c-H-ras; Transforming protein p21; HaRas; Ha-Ras; H-Ras-1; GTPase HRas, Nterminally processed

Small GTPase superfamily, Ras family

Small GTPase

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Involved in the activation of Ras protein signal transduction.

Costello syndrome (CSTLO) [MIM:218040]: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities. {ECO:0000269|PubMed:16170316, ECO:0000269|PubMed:16329078, ECO:0000269|PubMed:16443854, ECO:0000269|PubMed:17054105, ECO:0000269|PubMed:18039947, ECO:0000269|PubMed:18247425, ECO:0000269|PubMed:19995790}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]: Variant of Costello syndrome. {ECO:0000269|PubMed:17412879}. 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.; DISEASE: Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. {ECO:0000269|PubMed:3670300}.; DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. {ECO:0000269|PubMed:6298635, ECO:0000269|PubMed:6844927}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis. {ECO:0000269|PubMed:22683711}. The disease is caused by variants affecting the gene represented in this entry.

DB04315; DB04137; DB02210; DB08751; DB03226; DB15588

Q99996-3; P53677-2; P10398; Q9NXL2-1; Q9UII2; Q9H7T9; Q00994; Q9H2G9; P15056; Q7Z569; Q5PSV4; Q9ULD4-2; Q96LL4; Q96HB5; Q49A88-3; Q96GN5-2; P24941; O95674; Q9H3R5; Q9Y4F5-3; Q86XR8; Q494V2-2; Q8WUX9; Q14117; Q9Y6W6; O14641; A0AVK6; Q8NB25; Q8IZU1; O94868-3; P15407; P15408; P52655; Q96CS2; Q9BT25; Q8IV36; O43248; Q53GQ0; P10809; Q8NDH6-2; Q8IY31-2; Q8NA54; Q13352; P28290-2; Q9BVG8-5; Q2M2Z5; Q6P597; P57682; Q9UH77; P08727; Q14525; Q14847-2; Q96LR2; P27338; Q99558; Q96EZ8; Q8TAC0; Q5JXC2; Q8NEH6; Q9Y605; Q96HT8; Q9GZM8; P21359; Q8N5V2; Q6PHZ7; Q9BZ95-3; A5D8V7; O43482; Q9BR81; O15534; Q9BUL5; O00329; O00329-2; Q9UPR0; Q96I34; Q15435-3; P04049; P11233; Q15311; Q12967; Q9NS23-2; Q9NS23-4; Q8WWW0; Q8TBY0; Q9P2K3-2; Q9NZL6; O15211; Q8IXN7; Q13671; Q13671-1; Q8WVD3; Q9BY12-3; Q13435; Q12824; Q13573; Q07889; Q86W54-2; Q92783-2; O75886; Q13586; Q8N4C7; O75528; P54274-2; Q9BXU0; Q5T0J7-2; Q5T1C6; Q8IUR5-4; P36406; Q86WT6-2; Q99598; Q6PF05; Q9UGJ1-2; Q9Y5Z9; P22415; Q495M9; Q9H270; Q8NEZ2; P19544-6; O43829; Q9C0F3; Q7Z637; Q86V28; P42337; Q9Z0S9; Q9EQZ6; P27671; Q5EBH1; Q5EBH1-1; P52306-5

NA

3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Glycoprotein; Golgi apparatus; GTP-binding; Hydrolase; Isopeptide bond; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus; Palmitate; Prenylation; Proteomics identification; Proto-oncogene; Reference proteome; S-nitrosylation; Ubl conjugation

E,F

28737.2

259

0.1

30.69

5.64

-4.15

-10.09

NAAA

Homo sapiens (Human)

Nacylsphingosine amidohydrolaselike; Nacylethanolaminehydrolyzing acid amidase subunit beta; NAAA; Acid ceramidaselike protein; ASAHlike protein

Acid ceramidase family

Carbon-nitrogen hydrolase

Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N- palmitoylethanolamine > N-myristoylethanolamine > N- lauroylethanolamine = N-stearoylethanolamine > N- arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N- lauroylsphingosine and N-palmitoylsphingosine.

Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. {ECO:0000269|PubMed:22226083, ECO:0000269|PubMed:24549054}. The disease is caused by variants affecting the gene represented in this entry.

DB09061; DB14009; DB14011

NA

EC 3.5.1.-

3D-structure; Alternative splicing; Autocatalytic cleavage; Direct protein sequencing; Disulfide bond; Fatty acid metabolism; Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane; Proteomics identification; Reference proteome; Signal; Zymogen

A,B

36877.8

328

0.11

44.37

7.72

1.08

-10.09

HELPY mtnN

Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori)

MTAN; MTA/SAH nucleosidase; Aminofutalosine nucleosidase; Aminodeoxyfutalosine nucleosidase; AFL nucleosidase; 6-amino-6-deoxyfutalosine N-ribosylhydrolase; 5'-methylthioadenosine/S-adenosylhomocystei

PNP/UDP phosphorylase family

NA

Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Can also probably catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2. Does not act on futalosine (FL) as substrate.

Progressive familial heart block 1B (PFHB1B) [MIM:604559]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death. {ECO:0000269|PubMed:19726882, ECO:0000269|PubMed:20562447, ECO:0000269|PubMed:21887725}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Erythrokeratodermia variabilis et progressiva 6 (EKVP6) [MIM:618531]: A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP6 inheritance is autosomal dominant. {ECO:0000269|PubMed:30528822}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Amino-acid biosynthesis; Hydrolase; Menaquinone biosynthesis; Methionine biosynthesis; Reference proteome

A,B

50547.6

464

0.08

26.92

5.13

-20.92

-10.09