Fung SDH1

Pyricularia oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958) (Rice blast fungus) (Magnaporthe oryzae)

SDH1

Scytalone dehydratase family

Alpha-carbonic anhydrase

Catalyzes two steps in melanin biosynthesis. From scytalone they are two dehydration steps and one reduction step to yield melanin.

CODAS syndrome (CODASS) [MIM:600373]: A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts. {ECO:0000269|PubMed:25574826, ECO:0000269|PubMed:25808063}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 4.2.1.94

3D-structure; Calcium; Direct protein sequencing; Endosome; Lyase; Melanin biosynthesis; Metal-binding; Reference proteome

A

19102.4

162

0.14

31.72

5.87

-3.7

-10.4

MT-CO2

Homo sapiens (Human)

NA

MTCO2;COXII;COII;COX2

Cytochrome c oxidase subunit 2 family

Immune system

Copper ion binding.Cytochrome-c oxidase activity.

Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:10486321}. The disease is caused by variants affecting the gene represented in this entry.

DB02659; DB04464; DB05412

Q9NZ94-2; P49281-3

7.1.1.9

3D-structure; Copper; Disease variant; Electron transport; Magnesium; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; Proteomics identification; Reference proteome; Respiratory chain; Translocase; Transmembrane; Transmembrane helix; Transport

C

21687.9

189

0.11

38

5.68

-3.26

-10.38

NR1H3

Homo sapiens (Human)

Nuclear receptor subfamily 1 group H member 3; Nuclear receptor LXRalpha; Nuclear orphan receptor LXR-alpha; Liver X receptor alpha; LXRalpha; LXRA

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity.

Okur-Chung neurodevelopmental syndrome (OCNDS) [MIM:617062]: An autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and variable dysmorphic features. {ECO:0000269|PubMed:27048600}. The disease is caused by variants affecting the gene represented in this entry.

DB08175; DB08063; DB11994; DB07929; DB13174; DB07080

O60869; O60341; Q99750; Q15788; O75376; Q07869; Q07869-1; Q03181; P37231; P19793; P28702; P48443; O43463; P42858; Q99750; O95817; G5E9A7; O95872; P02545; Q99750; P28702; P28702-3; P48443; Q7Z699

NA

3D-structure; Activator; Alternative splicing; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

25389.9

220

0.09

46.42

5.51

-6.58

-10.38

MTNR1A

Homo sapiens (Human)

Mel1a receptor; Mel1AR; Mel-1A-R

G-protein coupled receptor 1 family

GPCR rhodopsin

Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. High affinity receptor for melatonin.

Spermatogenic failure 5 (SPGF5) [MIM:243060]: An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome. {ECO:0000269|PubMed:17435757, ECO:0000269|PubMed:21733974}. The disease is caused by variants affecting the gene represented in this entry.

DB06594; DB01065; DB00980; DB02709; DB09071

P27797; A8MQ03; Q8IUG1; P49286; O76081; P57088

NA

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

D

31301

276

0.15

37.33

9.22

9.92

-10.38

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

-10.37

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

-10.35

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

-10.35

cumD

Pseudomonas fluorescens

NA

NA

NA

Hydrolase

Hydrolase activity.

Intellectual developmental disorder, autosomal dominant 62 (MRD62) [MIM:618793]: An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development. {ECO:0000269|PubMed:27479843, ECO:0000269|PubMed:29460436}. The disease is caused by variants affecting the gene represented in this entry.

DB03741; DB03793; DB03568; DB02531; DB03750; DB02406; DB03766

NA

NA

3D-structure; Hydrolase

A

30307.9

271

0.1

37.49

5.02

-11.58

-10.35

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

-10.35

poxB

Escherichia coli (strain K12)

NA

b0871;JW0855

TPP enzyme family

Oxidoreductase

Flavin adenine dinucleotide binding.Identical protein binding.Lipid binding.Magnesium ion binding.Pyruvate dehydrogenase (quinone) activity.Thiamine pyrophosphate binding.

Glycogen storage disease 6 (GSD6) [MIM:232700]: A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. {ECO:0000269|PubMed:9529348}. The disease is caused by variants affecting the gene represented in this entry.

NA

P07003

1.2.5.1

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; FAD; Flavoprotein; Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Oxidoreductase; Pyruvate; Reference proteome; Thiamine pyrophosphate; Ubiquinone

A,B,C,D,E,F,G,H,I,J,K,L

113027

1046

0.07

35.99

5.75

-24.38

-10.34

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

-10.33

THRB

Homo sapiens (Human)

c-erbA-beta; c-erbA-2; THR1; Nuclear receptor subfamily 1 group A member 2; NR1A2; ERBA2

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

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

Thyroid hormone resistance, generalized, autosomal dominant (GRTHD) [MIM:188570]: An autosomal dominant disease characterized by high levels of circulating thyroid hormones (T3-T4), goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Patients have normal or slightly elevated thyroid stimulating hormone (TSH). {ECO:0000269|PubMed:10660344, ECO:0000269|PubMed:12511610, ECO:0000269|PubMed:12554782, ECO:0000269|PubMed:1314846, ECO:0000269|PubMed:1324420, ECO:0000269|PubMed:1563081, ECO:0000269|PubMed:1587388, ECO:0000269|PubMed:1619012, ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:16804041, ECO:0000269|PubMed:1846005, ECO:0000269|PubMed:19268523, ECO:0000269|PubMed:2153155, ECO:0000269|PubMed:2510172, ECO:0000269|PubMed:7833659, ECO:0000269|PubMed:8175986, ECO:0000269|PubMed:8514853, ECO:0000269|PubMed:8664910, ECO:0000269|PubMed:8889584}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid hormone resistance, generalized, autosomal recessive (GRTHR) [MIM:274300]: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. {ECO:0000269|PubMed:1653889}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. {ECO:0000269|PubMed:7528740, ECO:0000269|PubMed:8381821}. The disease is caused by variants affecting the gene represented in this entry.

DB08085; DB03181; DB02106; DB01118; DB00509; DB05035; DB03788; DB03176; DB00451; DB00279; DB01583; DB05192; DB07425; DB09100; DB03604

Q60974; Q9Y618

NA

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

A,B

27235.4

239

0.09

43.29

5.42

-8.55

-10.32

Malaria DHOdehase

Plasmodium falciparum (isolate 3D7)

PFF0160c; Mitochondrially bound dihydroorotate-ubiqui oxidoreductase; Dihydroorotate oxidase of Plasmodium falciparum; Dihydroorotate dehydrogenase of Plasmodium falciparum; DHOdehase of Plasmodium fa

Dihydroorotate dehydrogenase family, Type 2 subfamily

CH-CH donor oxidoreductase

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

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

EC 1.3.5.2

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

A

41846.8

371

0.1

37.25

8.21

3.13

-10.33

LCN2

Homo sapiens (Human)

p25; Siderocalin LCN2; Oncogene 24p3; NGAL; Lipocalin-2; LCN2; 25 kDa alpha-2-microglobulin-related subunit of MMP-9

Calycin superfamily, Lipocalin family

Calycin family

Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5- DHBA), a siderophore that shares structural similarities withbacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth. .

Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. {ECO:0000269|PubMed:10718838, ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800, ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320, ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368, ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313, ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837, ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434, ECO:0000269|PubMed:9843052}. The disease is caused by variants affecting the gene represented in this entry.

DB02710; DB01672; DB01926; DB04043; DB01631; DB04476

P49419-2; Q9NXW9; Q8WXI3; Q12797-6; Q9BXY8; Q96LC9; P49069; P24863; Q9UKJ5; Q9H1P6; Q9H6B4; O14595; Q08426; Q6NZ36-4; B3EWG5; Q7Z4H3; Q6ISS4; Q5TA76; P80188; Q9UIQ6-2; Q9Y6Y9; Q96JG8; Q8IXL7-2; Q969H8; Q969S2; Q17RF5; P07237; P13667; Q96FA3; Q9NRD5; Q13526; Q9UGP5-2; Q12837; P54646; Q86Y79; O60895; Q9BWG6; P60059; O43765; Q96EQ0; Q8IYX1; Q9UL33-2; P20396; O43715; Q13049; Q99816; Q5W5X9-3; Q99757; P57075-2; Q969M7; Q9UMX0; Q9UHD9; P15692-12; Q14119; Q9Y6T4; Q9H0D6; O96006; A0A1U9X8X8

NA

3D-structure; Alternative splicing; Apoptosis; Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity; Innate immunity; Ion transport; Iron; Iron transport; Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal; Transport

A

19748.4

172

0.13

30.73

7.71

0.72

-10.32

VEGFA

Homo sapiens (Human)

Vascular permeability factor; VPF; VEGF-A; VEGF

PDGF/VEGF growth factor family

Growth factor

Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development. Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth.

Microvascular complications of diabetes 1 (MVCD1) [MIM:603933]: 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. {ECO:0000269|PubMed:11978667}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB05434; DB08885; DB00112; DB06642; DB14864; DB01136; DB09301; DB06779; DB05932; DB15303; DB10772; DB01120; DB01017; DB04895; DB03088; DB01270; DB05969; DB05294; DB12317; DB05890

P17948; P35968; O14786; P15692; P17948; P35968; O14786-2; P15692-4; P08034; P80188; Q9NQQ7-3; Q96Q45-2

NA

3D-structure; Alternative initiation; Alternative promoter usage; Alternative splicing; Angiogenesis; Cytoplasm; Developmental protein; Differentiation; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Glycoprotein; Golgi apparatus; Growth factor; Heparin-binding; Mitogen; Nucleus; Proteomics identification; Reference proteome; Secreted

C,D

9393.81

89

0.08

31.48

6.89

-0.11

-10.31

PGR

Homo sapiens (Human)

PR; Nuclear receptor subfamily 3 group C member 3; NR3C3

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.

Butyrylcholinesterase deficiency (BCHED) [MIM:617936]: An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency. {ECO:0000269|PubMed:10404729, ECO:0000269|PubMed:11928765, ECO:0000269|PubMed:12881446, ECO:0000269|PubMed:1306123, ECO:0000269|PubMed:1349196, ECO:0000269|PubMed:1415224, ECO:0000269|PubMed:15563885, ECO:0000269|PubMed:15781196, ECO:0000269|PubMed:1611188, ECO:0000269|PubMed:16788378, ECO:0000269|PubMed:17700357, ECO:0000269|PubMed:18075469, ECO:0000269|PubMed:18300943, ECO:0000269|PubMed:25054547, ECO:0000269|PubMed:25264279, ECO:0000269|PubMed:2915989, ECO:0000269|PubMed:7634491, ECO:0000269|PubMed:8554068, ECO:0000269|PubMed:8680411, ECO:0000269|PubMed:9110359, ECO:0000269|PubMed:9191541, ECO:0000269|PubMed:9388484, ECO:0000269|PubMed:9543549, ECO:0000269|PubMed:9694584}. The disease is caused by variants affecting the gene represented in this entry.

DB01431; DB06680; DB01406; DB12941; DB13857; DB00304; DB09123; DB01395; DB00378; DB11219; DB00823; DB00294; DB13867; DB08906; DB00588; DB06730; DB11619; DB11064; DB06789; DB00367; DB00431; DB09124; DB00603; DB00351; DB02998; DB00834; DB00648; DB00764; DB14512; DB06713; DB00717; DB00957; DB09389; DB01428; DB02746; DB00396; DB14583; DB00421; DB04787; DB05253; DB08867

Q9H467; P03372; P06401; P40763; P03372

NA

3D-structure; Alternative promoter usage; Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein; Membrane; Metal-binding; Mitochondrion; Mitochondrion outer membrane; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A,B

28853.6

250

0.09

54.82

8.4

2.28

-10.31

NR1H4

Homo sapiens (Human)

NA

HRR1;BAR;RIP14;FXR

Nuclear hormone receptor family, NR1 subfamily

Transcription

Bile acid binding.Bile acid receptor activity.Chenodeoxycholic acid binding.Ligand-dependent nuclear receptor binding.Retinoid X receptor binding.RNA polymerase II distal enhancer sequence-specific DNA binding.RNA polymerase II regulatory region sequence-specific DNA binding.RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding.Sequence-specific DNA binding.Steroid hormone receptor activity.Thyroid hormone receptor activity.Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding.Transcriptional activator activity, RNA polymerase II transcription factor binding.Transcription coactivator activity.Transcription corepressor activity.Transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding.Transcription factor activity, sequence-specific DNA binding.Transcription regulatory region sequence-specific DNA binding.Zinc ion binding.

May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305|PubMed:17681172}.; DISEASE: May be involved in cholesterol cholelithiasis. {ECO:0000305|PubMed:17931734}.; DISEASE: Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. {ECO:0000269|PubMed:26888176}. The disease is caused by variants affecting the gene represented in this entry.

DB08220; DB00132; DB04557; DB06777; DB02659; DB03619; DB02509; DB02545; DB11605; DB16255; DB05990; DB04348; DB16343; DB01586

Q15788; O75151; Q8WTS6; P28702; P28702-3; P48443; Q15788; P78527; P03372

NA

3D-structure; Acetylation; Activator; Alternative promoter usage; Alternative splicing; Disease variant; DNA-binding; Immunity; Inflammatory response; Innate immunity; Intrahepatic cholestasis; Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

28271.2

241

0.08

47.06

5.39

-11.24

-10.31

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

-10.29

PTGDR2

Homo sapiens (Human)

PTGDR2; Chemoattractant receptor-homologous molecule expressed on Th2 cells; CD294

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin- sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, ADRBK1/GRK2, GPRK5/GRK5 and GRK6. Receptoractivation is responsible, at least in part, in immune regulation and allergic/inflammation responses.

Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA) [MIM:618922]: An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, hypotonia, severe to profound intellectual disability, early-onset epilepsy, and microcephaly. Neuroimaging shows cerebral atrophy, thin corpus callosum and hypomyelination in a majority of cases. Death in childhood may occur. {ECO:0000269|PubMed:27435318, ECO:0000269|PubMed:28097321, ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33476302, ECO:0000269|PubMed:33500274}. The disease is caused by variants affecting the gene represented in this entry.

DB00770; DB12789; DB00917; DB01088; DB00328; DB02056; DB13036; DB00605; DB04828

NA

NA

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

A

49740.6

447

0.1

37.89

10.13

21.88

-10.3

TK

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)

NA

UL23

Herpesviridae thymidine kinase family

Transferase

ATP binding.Thymidine kinase activity.

Atransferrinemia (ATRAF) [MIM:209300]: A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia. {ECO:0000269|PubMed:11110675, ECO:0000269|PubMed:15466165}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

2.7.1.21

3D-structure; ATP-binding; DNA synthesis; Early protein; Kinase; Nucleotide-binding; Reference proteome; Transferase

A,B

67808.8

624

0.07

43.94

6.1

-7.02

-10.28