R

Escherichia phage lambda (Bacteriophage lambda)

NA

NA

Glycosyl hydrolase 24 family

Glycosidase

Lyase activity.Lysozyme activity.Lytic transglycosylase activity.

Estrogen resistance (ESTRR) [MIM:615363]: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present. {ECO:0000269|PubMed:23841731, ECO:0000269|PubMed:27754803}. The disease is caused by variants affecting the gene represented in this entry.

DB04206

NA

4.2.2.n2

3D-structure; Antimicrobial; Bacteriolytic enzyme; Cytolysis; Direct protein sequencing; Host cell lysis by virus; Host cytoplasm; Lyase; Reference proteome; Viral release from host cell

A,B,C

49834.9

462

0.07

18.78

9.6

18.29

-5.44

FDPS

Homo sapiens (Human)

NA

KIAA1293;FPS

FPP/GGPP synthase family

Transferase

Dimethylallyltranstransferase activity.Geranyltranstransferase activity.Metal ion binding.RNA binding.

Porokeratosis 9, multiple types (POROK9) [MIM:616631]: A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported. {ECO:0000269|PubMed:26202976}. The disease is caused by variants affecting the gene represented in this entry.

DB00630; DB01785; DB07780; DB02552; DB07841; DB00710; DB06255; DB04714; DB02508; DB06548; DB00282; DB00884; DB00399

O95870; P54253; Q6ZMZ0; Q9BRI3; Q8WWF3

2.5.1.1; 2.5.1.10

3D-structure; Acetylation; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasm; Disease variant; Host-virus interaction; Hydroxylation; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase

A

38722.9

338

0.12

45.6

5.1

-9.86

-5.44

CYP17A1

Homo sapiens (Human)

Steroid 17-alpha-hydroxylase/17,20 lyase; P450c17; P450-C17; P450 17; CYPXVII; CYP17A1; CYP 17; 17 alpha-Hydroxylase/C17-20-lyase

Cytochrome P450 family

Paired donor oxygen oxidoreductase

Conversion of pregnenolone and progesterone to their 17- alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.

Adrenal hyperplasia 5 (AH5) [MIM:202110]: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). {ECO:0000269|PubMed:10720067, ECO:0000269|PubMed:11549685, ECO:0000269|PubMed:11836339, ECO:0000269|PubMed:12466376, ECO:0000269|PubMed:14671162, ECO:0000269|PubMed:1515452, ECO:0000269|PubMed:1714904, ECO:0000269|PubMed:1740503, ECO:0000269|PubMed:19793597, ECO:0000269|PubMed:24140098, ECO:0000269|PubMed:24498484, ECO:0000269|PubMed:25650406, ECO:0000269|PubMed:2808364, ECO:0000269|PubMed:8027220, ECO:0000269|PubMed:8245018, ECO:0000269|PubMed:8345056, ECO:0000269|PubMed:8396144, ECO:0000269|PubMed:8550762, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB05812; DB04630; DB01424; DB09061; DB00882; DB01234; DB14649; DB01026; DB05667; DB14009; DB14011; DB00157; DB01708; DB00396; DB02901

NA

EC 1.14.14.19

3D-structure; Congenital adrenal hyperplasia; Disease variant; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Steroidogenesis

A,B,C,D

51385.8

453

0.08

32.67

8.48

4.08

-5.45

PAH

Homo sapiens (Human)

Phenylalanine4hydroxylase; Phenylalanine-4-hydroxylase; Phe4monooxygenase; Phe-4-monooxygenase

Biopterin-dependent aromatic amino acid hydroxylase family

Paired donor oxygen oxidoreductase

Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.

Phenylalanine hydroxylase deficiency (PAH deficiency) [MIM:261600]: An autosomal recessive inborn error of phenylalanine metabolism characterized by intolerance to dietary intake of the essential amino acid phenylalanine. The disease spectrum depends on the degree of PAH deficiency and the phenylalanine levels in plasma. Severe deficiency causes classic phenylketonuria (PKU) that is characterized by plasma concentrations of phenylalanine persistently above 1200 umol/L. PKU patients develop profound and irreversible intellectual disability, unless low phenylalanine diet is introduced early in life. They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor. Less severe forms of PAH deficiency are characterized by phenylalanine levels above normal (120 umol/L) but below 1200 umol/L and include moderate PKU, mild PKU, non-PKU hyperphenylalaninemia (non-PKU HPA) and mild hyperphenylalaninemia. Individuals with PAH deficiency who have plasma phenylalanine concentrations consistently below 600 umol/L on an unrestricted diet are not at higher risk of developing intellectual, neurologic, and neuropsychological impairment than are individuals without PAH deficiency. {ECO:0000269|PubMed:10200057, ECO:0000269|PubMed:10679941, ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:11326337, ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:11935335, ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1301187, ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:1363837, ECO:0000269|PubMed:1363838, ECO:0000269|PubMed:1671810, ECO:0000269|PubMed:1672290, ECO:0000269|PubMed:1672294, ECO:0000269|PubMed:1679030, ECO:0000269|PubMed:1709636, ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:1975559, ECO:0000269|PubMed:2014802, ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:22526846, ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:2615649, ECO:0000269|PubMed:2840952, ECO:0000269|PubMed:32668217, ECO:0000269|PubMed:7833954, ECO:0000269|PubMed:8068076, ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:8406445, ECO:0000269|PubMed:8889583, ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9048935, ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9450897, ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062, ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453, ECO:0000269|PubMed:9634518, ECO:0000269|PubMed:9792407, ECO:0000269|PubMed:9792411, ECO:0000269|PubMed:9852673, ECO:0000269|PubMed:9950317}. The disease is caused by variants affecting the gene represented in this entry.

DB03673; DB04339; DB06778; DB04419; DB06262; DB04400; DB00368; DB00120; DB02562; DB00360

NA

EC 1.14.16.1

3D-structure; Allosteric enzyme; Direct protein sequencing; Disease variant; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Phenylalanine catabolism; Phenylketonuria; Phosphoprotein; Proteomics identification; Reference proteome

A

35556.1

307

0.15

39.96

6.17

-3.5

-5.44

BCHE

Homo sapiens (Human)

Pseudocholinesterase; Choline esterase II; CHE1; Butyrylcholine esterase; Acylcholine acylhydrolase

Type-B carboxylesterase/lipase family

Type-B carboxylesterase/lipase

Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.

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.

DB08200; DB08201; DB03814; DB07940; DB03672; DB03128; DB08897; DB01122; DB06692; DB01408; DB00868; DB06756; DB11148; DB03568; DB04250; DB06774; DB01161; DB00856; DB00477; DB00122; DB14006; DB00527; DB00515; DB04920; DB00907; DB00979; DB01245; DB00944; DB11397; DB02811; DB00711; DB00449; DB07681; DB00843; DB01135; DB01057; DB01010; DB01364; DB03822; DB08658; DB00674; DB00941; DB00762; DB06636; DB00677; DB01064; DB01221; DB00772; DB00888; DB00358; DB02845; DB08893; DB01226; DB09205; DB01400; DB00585; DB00892; DB01337; DB00082; DB00183; DB00790; DB04892; DB03976; DB01338; DB00733; DB01035; DB00721; DB00392; DB09288; DB00545; DB00178; DB05386; DB00989; DB05875; DB00202; DB00391; DB00382; DB00871; DB04572; DB14031; DB00620; DB00508; DB01116; DB01199

P54252; P46379-2; P06276; P55212; O75190-2; O14901; P13473-2; O75400-2; P62826; P67812; P02814

EC 3.1.1.8

3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Phosphoprotein; Proteomics identification; Reference proteome; Secreted; Serine esterase; Sialic acid; Signal

A

58935.5

523

0.13

38.71

8.63

5.36

-5.44

CYP19A1

Homo sapiens (Human)

P-450AROM; Estrogen synthetase; Estrogen synthase; Cytochrome P450 19A1; Cytochrome P-450AROM; CYPXIX; CYP19; CYAR; ARO1

Cytochrome P450 family

Paired donor oxygen oxidoreductase

Catalyzes the formation of aromatic C18 estrogens from C19 androgens.

Aromatase excess syndrome (AEXS) [MIM:139300]: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Aromatase deficiency (AROD) [MIM:613546]: A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries. {ECO:0000269|PubMed:24705274, ECO:0000269|PubMed:8265607, ECO:0000269|PubMed:8530621, ECO:0000269|PubMed:9211678}. The disease is caused by variants affecting the gene represented in this entry.

DB02342; DB00357; DB01217; DB00443; DB04794; DB06719; DB13009; DB00389; DB00269; DB00856; DB04839; DB01406; DB00255; DB00858; DB01127; DB14598; DB14600; DB00974; DB06423; DB00783; DB00655; DB00926; DB00990; DB04539; DB01026; DB01006; DB05667; DB00358; DB01065; DB00333; DB06710; DB01110; DB16236; DB05749; DB08804; DB03467; DB00184; DB09389; DB01229; DB05804; DB00481; DB05875; DB02901; DB06147; DB00675; DB00894; DB00624; DB13943; DB13944; DB13946; DB01007; DB00197

NA

EC 1.14.14.14

3D-structure; Alternative splicing; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Pseudohermaphroditism; Reference proteome; Transmembrane; Transmembrane helix

A

52141.6

452

0.1

36.02

8.45

4.41

-5.44

TF

Homo sapiens (Human)

Siderophilin; Serotransferrin; PRO1400; Beta-1 metal-binding globulin

Transferrin family

Transferrin

It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.

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.

DB01370; DB14517; DB14518; DB01294; DB14526; DB14527; DB11136; DB14528; DB14529; DB14530; DB00515; DB09130; DB11397; DB13949; DB14490; DB14491; DB14488; DB14501; DB14489; DB13257; DB06215; DB06784; DB05260; DB01592; DB00893; DB00677; DB06757; DB11182; DB14520; DB01593; DB14487; DB14533; DB14548

O43315; O00501; Q7Z7G2; Q9GZR5; Q9Y282; Q96KR6; P01350; P08034; Q8NBJ4; O15529; Q8TED1; Q7Z5P4; A8MZ59; O15173; Q96TC7; Q3KNW5; Q9BXS9-3; Q99523; O43278-2; Q8N9I0; P02786; Q4KMG9; Q9K0U9; Q09057; Q9K0V0; P02786

NA

3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Ion transport; Iron; Iron transport; Metal-binding; Methylation; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transport

A

35854.5

324

0.1

34.17

7.58

1.42

-5.44

COMT

Homo sapiens (Human)

S-COMT; MB-COMT; Catechol-O-methyltransferase; COMT

Class I-like SAM-binding methyltransferase superfamily, Cation-dependent O-methyltransferase family

Methyltransferase

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.

Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:15645182}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB07462; DB02342; DB02105; DB08049; DB00118; DB00714; DB03336; DB00286; DB00255; DB00841; DB00988; DB15488; DB00494; DB00668; DB00783; DB00977; DB01064; DB00968; DB01141; DB03907; DB04820; DB06152; DB11632; DB00252; DB01420; DB00323

Q6P5T0; P30518; Q8NFU1; Q8NHW4; P34972; Q96BA8; P50402; Q5JX71; O14843; O00258; P08034; O75712; Q9NTQ9; O95377; Q8TDT2; Q8N6U8; O15529; P31937; Q9H2F3; O95279; Q5SR56; A6NDP7; Q0D2K0; Q7RTS5; Q9UHJ9-5; Q8IY26; Q9H6H4; Q6NTF9-3; O75783; Q99500; Q9Y6D0; Q3KNW5; O60669; P22732; Q96G79; Q5T1Q4; Q9NY26; Q9NP94; Q6P1K1; P30825; Q9UHI5; B2RUZ4; Q9UPZ6; Q96MV1; Q9NV29; A0PK00; Q9NUH8; Q9P0S9; Q14656; Q6UW68; Q9H0R3; O95807; P34981; Q15645; Q15836; O95183; O76024; P30260; Q9H816; Q92997; P29323-3; P22607; P06396; Q15323; Q6A162; P26371; O15116; P20645; O14744; Q5T160; Q9UJD0; Q2MKA7; Q8N488; O75880; Q14141; Q9UNE7; Q15645; Q9NYH9; Q8NA23-2

EC 2.1.1.6

3D-structure; Alternative initiation; Catecholamine metabolism; Cell membrane; Cytoplasm; Direct protein sequencing; Lipid metabolism; Magnesium; Membrane; Metal-binding; Methyltransferase; Neurotransmitter degradation; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Schizophrenia; Signal-anchor; Transferase; Transmembrane; Transmembrane helix

A

23851.2

214

0.07

25.99

5.25

-7.75

-5.45

SHMT1

Homo sapiens (Human)

NA

NA

SHMT family

Transferase

Glycine hydroxymethyltransferase activity.Identical protein binding.L-allo-threonine aldolase activity.MRNA 5'-UTR binding.Protein homodimerization activity.Pyridoxal phosphate binding.Serine binding.Translation repressor activity, nucleic acid binding.

Deafness, autosomal dominant, 77 (DFNA77) [MIM:618915]: A form of non-syndromic deafness characterized by adult onset of bilateral, postlingual, mild-to-severe sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:31273342}. The gene represented in this entry is involved in disease pathogenesis.

DB02800; DB00145; DB01055; DB02824; DB00114; DB00116; DB02067

P26196; Q9H8Y8; P50213; P45984; Q99750; P34896; P0DMM9

2.1.2.1

3D-structure; Acetylation; Alternative splicing; Cytoplasm; One-carbon metabolism; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A

51456.1

470

0.08

37.11

6.78

-0.97

-5.45

ALDH1A3

Homo sapiens (Human)

NA

ALDH6

Aldehyde dehydrogenase family

Oxidoreductase

Aldehyde dehydrogenase (NAD) activity.Aldehyde dehydrogenase [NAD(P)+] activity.NAD+ binding.Protein homodimerization activity.Retinal dehydrogenase activity.Thyroid hormone binding.

Microphthalmia, isolated, 8 (MCOP8) [MIM:615113]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. {ECO:0000269|PubMed:23312594, ECO:0000269|PubMed:23591992, ECO:0000269|PubMed:23646827, ECO:0000269|PubMed:23881059, ECO:0000269|PubMed:24024553, ECO:0000269|PubMed:24568872, ECO:0000269|PubMed:24777706}. The disease is caused by variants affecting the gene represented in this entry.

DB00157; DB00162

NA

1.2.1.36

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Disease variant; Lipid metabolism; Microphthalmia; NAD; Oxidoreductase; Proteomics identification; Reference proteome

A,B,C,D,E,F,G,H

50635.7

461

0.09

33.75

7.07

0.15

-5.45

GFER

Homo sapiens (Human)

NA

HERV1;HPO;ALR

NA

Oxidoreductase

Flavin adenine dinucleotide binding.Flavin-linked sulfhydryl oxidase activity.Growth factor activity.Protein disulfide oxidoreductase activity.

Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCD) [MIM:613076]: A disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. {ECO:0000269|PubMed:19409522, ECO:0000269|PubMed:20593814}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

Q9H8W4; PRO_0000449628 [P0DTD1]

1.8.3.2

3D-structure; Alternative splicing; Cataract; Cytoplasm; Deafness; Disease variant; Disulfide bond; FAD; Flavoprotein; Growth factor; Mitochondrion; Oxidoreductase; Phosphoprotein; Primary mitochondrial disease; Proteomics identification; Reference proteome; Secreted

A

14170.4

126

0.11

48.59

6.58

-0.98

-5.44

CDK6

Homo sapiens (Human)

Serine/threonine-protein kinase PLSTIRE; Serine/threonine protein kinase PLSTIRE; Cell division protein kinase 6; CDKN6

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily

Kinase

Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e. g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases. Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.

Microcephaly 12, primary, autosomal recessive (MCPH12) [MIM:616080]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:23918663}. The disease is caused by variants affecting the gene represented in this entry.

DB07379; DB12001; DB03496; DB07795; DB09073; DB11730; DB15442

P41238; Q8N5C1; P24385; P30281; P51946; Q14094; Q16543; P38936; P42771; P42772; P42773; P55273; Q08050-1; P08238; Q5XKR4; Q01196; Q9C019

EC 2.7.11.22

3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; Cell projection; Cytoplasm; Cytoskeleton; Differentiation; Disease variant; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Primary microcephaly; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

A

29850.2

263

0.1

34.55

7.23

0.46

-5.44

ACY1

Homo sapiens (Human)

NA

NA

Peptidase M20A family

Hydrolase

Aminoacylase activity.Identical protein binding.Metal ion binding.Metallopeptidase activity.

Aminoacylase-1 deficiency (ACY1D) [MIM:609924]: An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids. {ECO:0000269|PubMed:16274666, ECO:0000269|PubMed:16465618, ECO:0000269|PubMed:17562838, ECO:0000269|PubMed:21414403}. The disease is caused by variants affecting the gene represented in this entry.

DB06151; DB00128; DB09130

Q03154; O75934; Q96HA8; P36639; P36639-2; Q8TCT1; P0CG20; Q96A09; P54274; O43711; Q9UPN9; Q9NZC7-5

3.5.1.14

3D-structure; Alternative splicing; Cytoplasm; Disease variant; Hydrolase; Metal-binding; Proteomics identification; Reference proteome; Zinc

A,C

31172.2

275

0.11

36.46

6

-5.26

-5.45

abfD

Clostridium aminobutyricum

NA

NA

NA

Lyase

4-hydroxybutanoyl-CoA dehydratase activity.4 iron, 4 sulfur cluster binding.Metal ion binding.Oxidoreductase activity, acting on the CH-CH group of donors.Vinylacetyl-CoA delta-isomerase activity.

Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCD) [MIM:613076]: A disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. {ECO:0000269|PubMed:19409522, ECO:0000269|PubMed:20593814}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

4.2.1.120; 5.3.3.3

3D-structure; 4Fe-4S; Direct protein sequencing; FAD; Flavoprotein; Iron; Iron-sulfur; Isomerase; Lyase; Metal-binding; Multifunctional enzyme; Oxidoreductase

A,B,C,D

53954.2

485

0.08

35.47

5.83

-7.6

-5.44

mop

Megalodesulfovibrio gigas (Desulfovibrio gigas)

NA

NA

Xanthine dehydrogenase family

Oxidoreductase

2 iron, 2 sulfur cluster binding.Aldehyde dehydrogenase (FAD-independent) activity.Electron carrier activity.Metal ion binding.

LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. {ECO:0000269|PubMed:10896305, ECO:0000269|PubMed:9820300}.

DB02137

NA

1.2.99.7

2Fe-2S; 3D-structure; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase

A

96930.4

907

0.07

29.17

5.69

-17.56

-5.44

dps

Agrobacterium fabrum (strain C58 / ATCC 33970) (Agrobacterium tumefaciens (strain C58))

NA

Atu2477;AGR_C_4495

Dps family

Iron-binding protein

Ferric iron binding.Oxidoreductase activity, oxidizing metal ions.

Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) [MIM:616281]: An autosomal recessive syndrome characterized by severe psychomotor developmental delay, dysarthria, walking difficulties, moderately to severely impaired intellectual development, poor or absent speech, and progressive microcephaly. {ECO:0000269|PubMed:25758935}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

1.16.-.-

3D-structure; Cytoplasm; Iron; Iron storage; Metal-binding; Oxidoreductase; Reference proteome

A,B,C,D,E,F

106227

967

0.06

22.32

5.52

-34.69

-5.44

WARS2

Homo sapiens (Human)

NA

NA

Class-I aminoacyl-tRNA synthetase family

Ligase / antibiotic

ATP binding.Tryptophan-tRNA ligase activity.

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) [MIM:617710]: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals. {ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:28650581, ECO:0000269|PubMed:28905505, ECO:0000269|PubMed:30920170, ECO:0000269|PubMed:35074316}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinsonism-dystonia 3, childhood-onset (PKDYS3) [MIM:619738]: An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. {ECO:0000269|PubMed:29120065, ECO:0000269|PubMed:31970218, ECO:0000269|PubMed:34890876}. The disease is caused by variants affecting the gene represented in this entry.

DB00150

NA

6.1.1.2

3D-structure; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Disease variant; Dystonia; Ligase; Mitochondrion; Nucleotide-binding; Parkinsonism; Primary mitochondrial disease; Protein biosynthesis; Proteomics identification; Reference proteome; Transit peptide

A,B

36376.7

327

0.06

51.57

8.75

4.55

-5.44

KLK2

Homo sapiens (Human)

hGK-1; Tissue kallikrein-2; Kallikrein-2; Glandular kallikrein-1

Peptidase S1 family, Kallikrein subfamily

Peptidase

Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.

Nivelon-Nivelon-Mabille syndrome (NNMS) [MIM:600092]: An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present. {ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:30912300}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.21.35

3D-structure; Alternative splicing; Disulfide bond; Glycoprotein; Hydrolase; Protease; Proteomics identification; Reference proteome; Serine protease; Signal; Zymogen

A

24954.3

227

0.08

43.7

6.42

-2.35

-5.44

LRRK2

Homo sapiens (Human)

PARK8; Leucine-rich repeat serine/threonine-protein kinase 2; Dardarin

Protein kinase superfamily, TKL Ser/Thr protein kinase family

Kinase

Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease. Plays an important role in recuiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization.

Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. {ECO:0000269|PubMed:15541308, ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:15680455, ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457, ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108, ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371, ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:15925109, ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16102999, ECO:0000269|PubMed:16157901, ECO:0000269|PubMed:16157908, ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16240353, ECO:0000269|PubMed:16247070, ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164, ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482, ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:16333314, ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18213618, ECO:0000269|PubMed:21641266, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421}. The disease is caused by variants affecting the gene represented in this entry.

DB12010

Q9UKV8; O43865; P31749; Q8N8V4; O00203; Q8N6T3-2; Q14155; O95816; O95817; Q9UL15; P10415-1; Q13191; Q16543; P60953; Q9UKI2; Q9Y6A4; P05060; Q9ULV4; P48729-1; P48730-2; Q9NWM3; P53355; Q05193; O00429; O00429-3; O14640-2; O14641; Q92997; P30084; Q05639; Q13158; O14976; P49841; P11142; Q71RC2; Q4G0J3; P07195; O75581; Q38SD2; Q5S007; PRO_0000018605 [P46821]; P46734; P52564; O14733; P10636-2; P10636-8; P42679; O95140; P49406; P26038; Q7L592; Q96PY6; Q13469; Q8WUM0; O60313; Q9NQU5; P62136; Q12972; P63151; P30048; P17612; O60260; P61026; Q6IQ22; Q9H0U4; O14966; Q13637; P57729; P61020; P61006; P63000; P41220; P62906; P26373; P50914; P62750; P62888; P49207; Q9BUL9; P62280; P62277; P62841; P62249; P62269; P15880; P60866; P62266; P42677; P23396; O15027; P60896; P31947; Q99961; Q99962; P12235; P05141; P12236; O95295; P37840; Q8NHS9; Q13501; Q9UNE7; Q9UNE7-1; Q9BQ70; Q6P3X3; P07437; Q13885; P04350; P68371; Q9BUF5; Q53GS9; P21796; Q9Y6I7; P31946; P62258; P61981; Q04917; P27348; P63104; O95218; Q62848; O55143; P30275; P39053; P02687; Q811U4; P00634; P12369; Q63481; P61021; Q58A65; Q9WUD1; P61983

EC 2.7.11.1

3D-structure; ATP-binding; Autophagy; Cell projection; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Differentiation; Disease variant; Endoplasmic reticulum; Endosome; Golgi apparatus; GTP-binding; GTPase activation; Hydrolase; Kinase; Leucine-rich repeat; Lysosome; Membrane; Mitochondrion; Mitochondrion outer membrane; Neurodegeneration; Nucleotide-binding; Parkinson disease; Parkinsonism; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Serine/threonine-protein kinase; Synapse; Transferase; Ubl conjugation; WD repeat

A

203267

1795

0.07

41.82

7.73

6.9

-5.44

CUL4A/CUL4B-DDB1-CRBN

Homo sapiens (Human)

NA

Cullin family

NA

NA

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

NA

P54253; Q86VP6; Q16531; Q92466; P08238; O94888; P55072

NA

3D-structure; Alternative splicing; Biological rhythms; DNA damage; DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway

B

42669.7

368

0.1

44.94

8.72

6.58

-5.44