HIV nef

Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2) (HIV-1)

nef; Nef protein; F-protein; 3'ORF; 27 kDa protein

Lentivirus primate group Nef protein family

Lentivirus primate group Nef

Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors.

Neurodegeneration due to cerebral folate transport deficiency (NCFTD) [MIM:613068]: An autosomal recessive neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy. {ECO:0000269|PubMed:19732866}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q14457; P01730

NA

3D-structure; AIDS; Apoptosis; Early protein; Host cell membrane; Host Golgi apparatus; Host membrane; Host-virus interaction; Inhibition of host adaptive immune response by virus; Inhibition of host autophagy by virus; Inhibition of host MHC class I molecule presentation by virus; Inhibition of host MHC class II molecule presentation by virus; Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome; Secreted; SH3-binding; Viral immunoevasion; Virion; Virulence

A,B

29232.1

245

0.16

50.97

5.71

-7.32

-5.46

AADAT

Homo sapiens (Human)

Kynurenineoxoglutarate transaminase II; Kynurenineoxoglutarate transaminase 2; Kynurenineoxoglutarate aminotransferase II; Kynurenine/alphaaminoadipate aminotransferase, mitochondrial; Kynurenine amin

Class-I pyridoxal-phosphate-dependent aminotransferase family

Transaminase

Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino- group acceptors, with a preference for 2-oxoglutarate, 2- oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).

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.

DB00142; DB00114

NA

EC 2.6.1.39

3D-structure; Acetylation; Alternative splicing; Aminotransferase; Mitochondrion; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide

A,B

91792.6

824

0.09

47.71

5.96

-8.73

-5.45

CTSV

Homo sapiens (Human)

UNQ268/PRO305; Cathepsin U; Cathepsin L2; CTSU; CTSL2; CATL2

Peptidase C1 family

Peptidase

May have an important role in corneal physiology. Cysteine protease.

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

DB02869; DB04451

P07711

EC 3.4.22.43

3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Protease; Proteomics identification; Reference proteome; Signal; Thiol protease; Zymogen

A

24013.7

221

0.11

16.86

8.4

2.96

-5.45

AOX1

Homo sapiens (Human)

AOX1

Xanthine dehydrogenase family

Aldehyde/oxo donor oxidoreductase

Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N- methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir topenciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.

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.

DB00437; DB00513; DB00484; DB11791; DB00215; DB00924; DB03516; DB01175; DB00426; DB12466; DB09054; DB09078; DB00170; DB01033; DB00563; DB08840; DB00157; DB00339; DB00481; DB04827; DB00962; DB00246; DB00909

Q06278

EC 1.2.3.1

2Fe-2S; 3D-structure; Cytoplasm; FAD; Flavoprotein; Iron; Iron-sulfur; Lipid metabolism; Metal-binding; Molybdenum; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome

A,B

286845

2590

0.08

42.7

6.92

-1.62

-5.46

LANCL1

Homo sapiens (Human)

p40; LanC-like protein 1; GPR69A; 40 kDa erythrocyte membrane protein

LanC-like protein family

NA

Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (By similarity). May play a role in EPS8 signaling. Binds glutathione.

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.

NA

Q9UHR4; P42858; Q08509

EC 2.5.1.18

3D-structure; Acetylation; Cell membrane; Cytoplasm; Direct protein sequencing; Membrane; Metal-binding; Proteomics identification; Reference proteome; Transferase; Zinc

A

46005.4

405

0.14

33.7

7.13

0.4

-5.46

metF

Escherichia coli (strain K12)

NA

b3941;JW3913

Methylenetetrahydrofolate reductase family

Oxidoreductase

FAD binding.Methylenetetrahydrofolate reductase (NAD(P)H) activity.

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

DB03147

NA

1.5.1.54

3D-structure; Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD; Oxidoreductase; Reference proteome

A,C,E

30855.9

274

0.09

27.54

5.84

-4.61

-5.45

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

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

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

GGPS1

Homo sapiens (Human)

NA

NA

FPP/GGPP synthase family

Transferase

Dimethylallyltranstransferase activity.Farnesyltranstransferase activity.Geranyltranstransferase activity.Identical protein binding.Metal ion binding.

Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome (MDHLO) [MIM:619518]: An autosomal recessive disorder characterized by early-onset progressive muscle weakness, sensorineural hearing loss, and primary amenorrhea due to ovarian insufficiency. Some patients become wheelchair-bound by the second decade, whereas others have a milder phenotype and maintain independent ambulation into adulthood. Most patients have respiratory insufficiency. {ECO:0000269|PubMed:32403198}. The disease is caused by variants affecting the gene represented in this entry.

DB06830; DB06931; DB07221; DB08529; DB07410; DB07780; DB04695; DB02552; DB07841; DB00710; DB04714; DB07873; DB06548; DB00282; DB00399

O00244; O95749; O00560

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

3D-structure; Acetylation; Alternative splicing; Congenital muscular dystrophy; Cytoplasm; Deafness; Disease variant; Isoprene biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Proteomics identification; Reference proteome; Transferase

A,B,C,D,E,F

32872.4

284

0.11

41.09

6.17

-3.37

-5.44

PARP1

Homo sapiens (Human)

Protein poly-ADP-ribosyltransferase PARP1; Poly[ADP-ribose] synthetase-1; Poly[ADP-ribose] synthase 1; Poly(ADP-ribose)polymerase-1; PPOL; PARP-1; NAD(+)Poly [ADP-ribose] polymerase-1 ADP-ribosyltrans

ARTD/PARP family

Glycosyltransferases

Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.

Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. {ECO:0000269|PubMed:10448086, ECO:0000269|PubMed:11687750, ECO:0000269|PubMed:12925875, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:8506365, ECO:0000269|PubMed:8968745, ECO:0000269|PubMed:9540846, ECO:0000269|PubMed:9934985}. The disease is caused by variants affecting the gene represented in this entry.

DB04010; DB03509; DB03072; DB03722; DB03073; DB07787; DB07096; DB07330; DB02498; DB13877; DB02701; DB11793; DB02690; DB09074; DB12332; DB11760; DB00277; DB07232; DB01593; DB14487; DB14533; DB14548

Q8IW19; Q7Z2E3; P42574; P49715; Q86WJ1-1; P26358; Q01094; Q96L91; P11308; O60741; P09429; Q13007; Q9BQ69; P08651; Q9Y530; P09874; Q8N2W9; P46063; Q9NTX7; Q14684-1; O95863; P63165; P04637; P0CG48; Q14191; P18887; P54577; Q2M1K9; Q02085

EC 2.4.2.30

3D-structure; Acetylation; ADP-ribosylation; Allosteric enzyme; Apoptosis; Chromosome; Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Glycosyltransferase; Immunity; Innate immunity; Isopeptide bond; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger

A,B

36904

329

0.08

35.9

6.83

-0.44

-5.45

CDK4

Homo sapiens (Human)

NA

NA

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

Cell cycle

ATP binding.Cyclin binding.Cyclin-dependent protein serine/threonine kinase activity.Cyclin-dependent protein serine/threonine kinase regulator activity.Protein complex binding.

Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. {ECO:0000269|PubMed:7652577, ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, ECO:0000269|PubMed:9425228}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB12001; DB03496; DB12010; DB09073; DB02733; DB11730; DB15442

Q9UH17; P24385; P30279; P30281; Q16543; P50613; P38936; P46527; P49918; P42771; P42772; P42773; P55273; Q9UJC3; P08238; Q9UKT9; Q0VD86; P01106; Q9ULD0; P28749; Q08999; P09936; Q8N720

2.7.11.22

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; Cytoplasm; Disease variant; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

B

30138.4

267

0.09

36.2

5.78

-5.83

-5.44

camC

Pseudomonas putida (Arthrobacter siderocapsulatus)

NA

cyp101

Cytochrome P450 family

Oxidoreductase

Camphor 5-monooxygenase activity.Heme binding.Iron ion binding.

Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070, ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614]: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. {ECO:0000269|PubMed:25986071}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. {ECO:0000269|PubMed:28842795}. The disease is caused by variants affecting the gene represented in this entry.

DB03836; DB02617; DB02817; DB03627; DB04032; DB03031; DB02125; DB04501; DB01744; DB01663; DB01011; DB01703; DB01826; DB03540; DB02851

P00259

1.14.15.1

3D-structure; Cytoplasm; Direct protein sequencing; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase

A

45446.3

405

0.08

45.33

5.23

-16.08

-5.44

GLUD1

Homo sapiens (Human)

NA

GLUD

Glu/Leu/Phe/Val dehydrogenases family

Oxidoreductase

ADP binding.ATP binding.Glutamate dehydrogenase (NAD+) activity.Glutamate dehydrogenase [NAD(P)+] activity.GTP binding.Identical protein binding.Leucine binding.NAD+ binding.

Hyperinsulinemic hypoglycemia, familial, 6 (HHF6) [MIM:606762]: A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF6 is an autosomal dominant form characterized by hypoglycemia due to congenital hyperinsulinism combined with persistent hyperammonemia. Clinical features include loss of consciousness due to hypoglycemia, hypoglycemic seizures, and mental retardation. {ECO:0000269|PubMed:10636977, ECO:0000269|PubMed:11214910, ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:9571255}. The disease is caused by variants affecting the gene represented in this entry.

DB11081; DB00142; DB04137; DB00756; DB00157

P49448

1.4.1.3

3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; ATP-binding; Direct protein sequencing; Disease variant; Endoplasmic reticulum; GTP-binding; Hydroxylation; Mitochondrion; NADP; Nucleotide-binding; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A,B,C,D,E,F

49471.9

447

0.09

27.17

7.3

0.81

-5.44

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

MTHFD2

Homo sapiens (Human)

NA

NMDMC

Tetrahydrofolate dehydrogenase/cyclohydrolase family

Oxidoreductase

Magnesium ion binding.Methenyltetrahydrofolate cyclohydrolase activity.Methylenetetrahydrofolate dehydrogenase (NAD+) activity.Methylenetetrahydrofolate dehydrogenase (NADP+) activity.Phosphate ion binding.

Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:17236137, ECO:0000269|PubMed:2063868}. The disease is caused by variants affecting the gene represented in this entry.

DB00157; DB00116

Q9UJ70-2

1.5.1.15; 3.5.4.9

3D-structure; Acetylation; Alternative splicing; Hydrolase; Isopeptide bond; Magnesium; Mitochondrion; Multifunctional enzyme; NAD; NADP; One-carbon metabolism; Oxidoreductase; Proteomics identification; Reference proteome; Transit peptide; Ubl conjugation

A

31600.3

292

0.03

27.9

8

1.64

-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

CAD

Homo sapiens (Human)

CAD

CarA family; CarB family; Metallo-dependent hydrolases superfamily, DHOase family, CAD subfamily; Aspartate/ornithine carbamoyltransferase superfamily, ATCase family

Carbon-nitrogen ligase

This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).

Developmental and epileptic encephalopathy 50 (DEE50) [MIM:616457]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine. {ECO:0000269|PubMed:25678555, ECO:0000269|PubMed:28087732}. The disease is caused by variants affecting the gene represented in this entry.

DB00128; DB00130; DB03459

P27708; Q8N137; P63104

NA

3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Congenital disorder of glycosylation; Cytoplasm; Direct protein sequencing; Disease variant; Epilepsy; Hydrolase; Ligase; Magnesium; Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Pyrimidine biosynthesis; Reference proteome; Repeat; Transferase; Zinc

A

38268.4

351

0.06

41.29

5.86

-10.56

-5.45

HPD

Homo sapiens (Human)

NA

PPD

4HPPD family

Oxidoreductase

4-hydroxyphenylpyruvate dioxygenase activity.Metal ion binding.

Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild intellectual disability. {ECO:0000269|PubMed:10942115, ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hawkinsinuria (HWKS) [MIM:140350]: An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. {ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.

DB02850; DB00348

NA

1.13.11.27

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Dioxygenase; Disease variant; Endoplasmic reticulum; Golgi apparatus; Intellectual disability; Iron; Membrane; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Tyrosine catabolism

A

43164.8

376

0.11

32.38

6.73

-1.04

-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

-5.45