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

-7.91

soxA

Bacillus sp. (strain B-0618)

NA

sox

MSOX/MTOX family, MSOX subfamily

Oxidoreductase

Sarcosine oxidase activity.

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

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

NA

1.5.3.1

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

A,B

42606.4

385

0.1

26.97

5.27

-17.18

-7.91

SULT1E1

Homo sapiens (Human)

NA

STE

Sulfotransferase 1 family

Transferase

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

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

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

O76083; O76083-2

2.8.2.4

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

A,B

34022.7

285

0.15

32.76

6.33

-2.75

-7.9

PTPRZ1

Homo sapiens (Human)

Receptor protein tyrosine phosphatase zeta; R-PTP-zeta; PTPRZ1

Protein-tyrosine phosphatase family, Receptor class 5 subfamily

Phosphoric monoester hydrolase

Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades.

Optic atrophy 1 (OPA1) [MIM:165500]: A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density. {ECO:0000269|PubMed:11017079, ECO:0000269|PubMed:11017080, ECO:0000269|PubMed:11440988, ECO:0000269|PubMed:11440989, ECO:0000269|PubMed:11810270, ECO:0000269|PubMed:12036970, ECO:0000269|PubMed:12566046, ECO:0000269|PubMed:14961560, ECO:0000269|PubMed:15948788, ECO:0000269|PubMed:16513463, ECO:0000269|PubMed:16617242, ECO:0000269|PubMed:18204809, ECO:0000269|PubMed:18360822, ECO:0000269|PubMed:19319978, ECO:0000269|PubMed:19325939, ECO:0000269|PubMed:19969356, ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:22382025, ECO:0000269|PubMed:22857269, ECO:0000269|PubMed:23401657}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Dominant optic atrophy plus syndrome (DOA+) [MIM:125250]: A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes. {ECO:0000269|PubMed:15531309, ECO:0000269|PubMed:16240368, ECO:0000269|PubMed:18065439, ECO:0000269|PubMed:18158317, ECO:0000269|PubMed:18195150, ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:21112924, ECO:0000269|PubMed:23387428}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Behr syndrome (BEHRS) [MIM:210000]: An autosomal recessive syndrome characterized by optic atrophy beginning in early childhood associated with ataxia, pyramidal signs, spasticity, intellectual disability, and posterior column sensory loss. The ataxia, spasticity, and muscle contractures, mainly of the hip adductors, hamstrings, and soleus, are progressive and become more prominent in the second decade. {ECO:0000269|PubMed:21636302, ECO:0000269|PubMed:25012220, ECO:0000269|PubMed:25146916}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 14, cardioencephalomyopathic type (MTDPS14) [MIM:616896]: An autosomal recessive mitochondrial disorder characterized by lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Skeletal muscle biopsies show significant mtDNA depletion and abnormal mitochondria. {ECO:0000269|PubMed:26561570}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UM73; Q12860

EC 3.1.3.48

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Phosphoprotein; Protein phosphatase; Proteoglycan; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transmembrane; Transmembrane helix

A

32208.1

282

0.11

38.98

7.35

0.89

-7.91

MT-CYB

Bos taurus (Bovine)

NA

CYTB;MTCYB;COB

Cytochrome b family

NA

Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000269|PubMed:1327781, ECO:0000269|PubMed:20025846, ECO:0000269|PubMed:9485330, ECO:0000305|PubMed:189810}."

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.

NA

NA

NA

3D-structure; Electron transport; Heme; Iron; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; Transport; Ubiquinone

C,D,F,G,H

99281.2

866

0.12

43.81

8.32

7.12

-7.89

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

-7.9

CD274

Homo sapiens (Human)

hPD-L1; Programmed death ligand 1; PDL1; PDCD1LG1; PDCD1L1; PDCD1 ligand 1; B7H1; B7-H1; B7 homolog 1

Immunoglobulin superfamily, BTN/MOG family

Immunoglobulin

As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response. Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10). Plays a critical role in induction and maintenance of immune tolerance to self.

Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199). {ECO:0000269|PubMed:27281199}.

DB15773; DB11595; DB15771; DB11945; DB15772; DB14776; DB15770; DB11714; DB15769; DB09035; DB09037; DB00203; DB00313

P33681; Q8IZR5; Q9NX76; Q15116; Q15116

NA

3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; Disulfide bond; Endosome; Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Nucleus; Proteomics identification; Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane; Transmembrane helix; Ubl conjugation

C,D

28335.2

249

0.1

35.39

6.15

-3.43

-7.9

MIF

Homo sapiens (Human)

Phenylpyruvate tautomerase; MMIF; L-dopachrome tautomerase; L-dopachrome isomerase; Glycosylation-inhibiting factor; GLIF; GIF

MIF family

Intramolecular oxidoreductase

Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. Pro-inflammatory cytokine.

Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:11508429}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB01880; DB07888; DB08334; DB08335; DB08333; DB07718; DB08765; DB02728

O43521-2; P00533; Q92743; P14174; Q96HA8

EC 5.3.2.1

3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Isomerase; Proteomics identification; Reference proteome; Secreted

A,C

24671.9

228

0.09

31.45

8.37

2.26

-7.89

MDM4

Homo sapiens (Human)

Protein Mdmx; Mdm2-like p53-binding protein; Double minute 4 protein

MDM2/MDM4 family

MDM2/MDM4 family

Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.

Bone marrow failure syndrome 6 (BMFS6) [MIM:618849]: A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer. {ECO:0000269|PubMed:32300648}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NX04; P10415; Q7Z479; O95971; P48729; Q00987; Q13064; P41227; P06400; Q9Y4L5; P23297; P29034; P33763; P04271; P31947; P04637; P62837; Q93009; O14972; P61964; P62258; P61981; P63104; Q9BRR0; A0A0S2Z6X0; Q3YBA8; P03255-2

NA

3D-structure; Alternative splicing; Disease variant; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Zinc; Zinc-finger

A,B

19722

173

0.08

50.78

8.48

2.27

-7.89

HRH1

Homo sapiens (Human)

HH1R; H1R

G-protein coupled receptor 1 family

GPCR rhodopsin

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.

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

DB01615; DB09488; DB06766; DB01246; DB00321; DB00543; DB08799; DB01238; DB14185; DB06216; DB00637; DB00719; DB00972; DB00245; DB00767; DB04890; DB06698; DB11591; DB09128; DB01237; DB00835; DB00354; DB09016; DB00748; DB06016; DB00341; DB08936; DB08800; DB01114; DB00477; DB01239; DB00568; DB00215; DB00283; DB04837; DB00363; DB01176; DB00434; DB01151; DB00967; DB00405; DB09555; DB00985; DB08801; DB01075; DB01146; DB09167; DB01142; DB00366; DB01084; DB05492; DB00751; DB01175; DB06678; DB00950; DB04841; DB00502; DB05381; DB05079; DB00557; DB04946; DB00458; DB08802; DB00920; DB00555; DB01106; DB06282; DB00455; DB09195; DB00408; DB00934; DB00737; DB06691; DB01071; DB00902; DB01403; DB06148; DB00370; DB00540; DB05080; DB06229; DB00334; DB00768; DB01173; DB01267; DB00715; DB08922; DB01619; DB01620; DB06153; DB00433; DB00420; DB01069; DB00777; DB01224; DB00912; DB00734; DB11614; DB05345; DB00342; DB04905; DB11235; DB00797; DB00656; DB00726; DB00792; DB00427; DB09185; DB00246; DB01624

NA

NA

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

R

32298.5

275

0.15

36.59

9.54

16.01

-7.88

RARA

Homo sapiens (Human)

RAR-alpha; RAR alpha; Nuclear receptor subfamily 1 group B member 1; NR1B1

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Receptor for retinoic acid.

Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. {ECO:0000269|PubMed:12691149, ECO:0000269|PubMed:8302850, ECO:0000269|PubMed:8562957}.

DB00459; DB00210; DB00523; DB00926; DB00982; DB05785; DB04942; DB00799; DB00755; DB12808

O43707-1; O15296; Q15699; Q96RK4; O95273; P51946; Q15910; P50148; Q9UKP3; Q96EZ8; Q15648; Q71SY5; Q15788; Q9Y6Q9; O75376; Q9Y618; Q16236; P13056-2; P48552; Q9UPP1-2; Q9H8W4; P37231; P78527; P19793; P28702; P28702-3; P48443; Q96EB6; P63165; Q8WW24; Q2M1K9; Q91XC0; P59598; Q14457; P48552; Q96CV9; P28702; P48443; Q8WW24

NA

3D-structure; Alternative splicing; Chromosomal rearrangement; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

27724.1

244

0.05

50.8

5.82

-3.61

-7.87

DBH

Homo sapiens (Human)

NA

NA

Copper type II ascorbate-dependent monooxygenase family

Oxidoreductase

Catalytic activity.Copper ion binding.Dopamine beta-monooxygenase activity.L-ascorbic acid binding.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB00126; DB06774; DB09130; DB05394; DB00822; DB00988; DB00968; DB00550

P00352; P63010-2; Q04656; Q8WUW1; Q9UNS2; Q71DI3; P61978; Q9Y2M5; Q92876; P08727; Q14693; P0DPK4; Q6GQQ9-2; P27986-2; Q9ULX5; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q86WT6-2

1.14.17.1

3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C

A,B

123694

1094

0.1

51.85

5.84

-24.5

-7.88

SDS

Homo sapiens (Human)

NA

SDH

Serine/threonine dehydratase family

Lyase

L-serine ammonia-lyase activity.L-threonine ammonia-lyase activity.Protein homodimerization activity.Pyridoxal phosphate binding.

Immunodeficiency, common variable, 12, with autoimmunity (CVID12) [MIM:616576]: A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. The disease is caused by variants affecting the gene represented in this entry.

DB00114; DB00133

Q8WTU0; O14964; Q96PF1

4.3.1.17; 4.3.1.19

3D-structure; Cytoplasm; Direct protein sequencing; Gluconeogenesis; Lipid metabolism; Lyase; Proteomics identification; Pyridoxal phosphate; Reference proteome

A

33559.7

319

0.06

34.65

7.2

0.42

-7.87

N/A

Plasmodium falciparum (isolate HB3)

NA

NA

Peptidase A1 family

Hydrolase

Aspartic-type endopeptidase activity.

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]: Autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features. {ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:16317551}. The disease is caused by variants affecting the gene represented in this entry.

DB04378; DB04373; DB11638; DB01218; DB02505; DB03063

NA

3.4.23.39

3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond; Hydrolase; Membrane; Protease; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Vacuole; Zymogen

A

36923.5

329

0.13

44.31

4.67

-17.94

-7.87

TPMT

Homo sapiens (Human)

NA

NA

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

Transferase

Thiopurine S-methyltransferase activity.

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

DB00993; DB00436; DB01327; DB01033; DB01250; DB01021

Q8TAP4-4; Q15047-2; P61981

2.1.1.67

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

A

25971.5

229

0.12

32.58

6.74

-0.6

-7.87

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

-7.87

Malaria DXR

Plasmodium falciparum (isolate HB3)

IspC; DXR; DXP reductoisomerase; DOXP reductoisomerase; 2-C-Methyl-d-erythritol 4-phosphate synthase; 1-deoxyxylulose-5-phosphate reductoisomerase

DXR family

Short-chain dehydrogenases reductase

Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).

Ichthyosis, congenital, autosomal recessive 11 (ARCI11) [MIM:602400]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:17273967, ECO:0000269|PubMed:18843291}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.1.1.267

3D-structure; Apicoplast; Isoprene biosynthesis; Magnesium; Manganese; Metal-binding; NADP; Oxidoreductase; Plastid; Transit peptide

A

46644.4

410

0.09

36.77

6.95

-0.14

-7.86

WNT7A

Homo sapiens (Human)

Protein Wnt-7a

Wnt family

NA

Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development. Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes. Required for normal neural stem cell proliferation in the hippocampus dentate gyrus. Required for normal progress through the cell cycle in neural progenitor cells, for self-renewal of neural stem cells, and for normal neuronal differentiation and maturation. Promotes formation of synapses via its interaction with FZD5. Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.

Limb pelvis hypoplasia aplasia syndrome (LPHAS) [MIM:276820]: A syndrome of severe deficiency of the extremities due to hypo- or aplasia of one or more long bones of one or more limbs. Pelvic manifestations include hip dislocation, hypoplastic iliac bone and aplastic pubic bones. Thoracic deformity, unusual facies and genitourinary anomalies can be present. {ECO:0000269|PubMed:16826533, ECO:0000269|PubMed:17431918, ECO:0000269|PubMed:20949531, ECO:0000269|PubMed:21271649, ECO:0000269|PubMed:27638328}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fuhrmann syndrome (FUHRS) [MIM:228930]: Distinct limb-malformation disorder characterized also by various degrees of limb aplasia/hypoplasia and joint dysplasia. {ECO:0000269|PubMed:16826533}. The disease is caused by variants affecting the gene represented in this entry.

NA

P55212; P22607; P06396; P13473-2; Q9UMX0; Q9Y5W5; Q5T9L3; Q9Z0J1

NA

3D-structure; Developmental protein; Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein; Lipoprotein; Proteomics identification; Reference proteome; Secreted; Signal; Wnt signaling pathway

A,B

40475.5

356

0.1

50.49

7.67

1.62

-7.87

AKR1B1

Homo sapiens (Human)

Aldehyde reductase; AKR1B1

Aldo/keto reductase family

Short-chain dehydrogenases reductase

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.

Glutamine deficiency, congenital (GLND) [MIM:610015]: An autosomal recessive disorder characterized by variable brain malformations, encephalopathy, severe developmental delay, seizures, and decreased glutamine levels in bodily fluids. Death in early infancy may occur. {ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 116 (DEE116) [MIM:620806]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE116 is autosomal dominant form characterized by severe developmental delay, seizures, and white matter abnormalities. {ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry. DEE116 is caused by variants that disrupt the canonical translation start codon in GLUL resulting in initiation of translation at Met-18 (PubMed:38579670). The resulting protein is enzymatically competent but insensitive to negative feedback regulation via glutamine-induced degradation. {ECO:0000269|PubMed:38579670}.

DB07028; DB07030; DB07450; DB02101; DB08449; DB08000; DB07139; DB07498; DB02007; DB02020; DB11859; DB02994; DB04272; DB07187; DB00694; DB00997; DB06246; DB01039; DB02021; DB16707; DB00143; DB02834; DB08084; DB01689; DB07063; DB06077; DB02518; DB00157; DB03461; DB05383; DB05533; DB05327; DB02712; DB00605; DB02383; DB02132; DB08772; DB07093; DB07999; DB08098

Q9BUY7

EC 1.1.1.300

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome

A

35447.6

313

0.09

36.41

7.1

0.26

-7.86

HRH3

Homo sapiens (Human)

Histamine receptor 3; HH3R; GPCR97; G-protein coupled receptor 97; G protein-coupled receptor 97

G-protein coupled receptor 1 family

GPCR rhodopsin

Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system.

Immunodeficiency 48 (IMD48) [MIM:269840]: A form of severe immunodeficiency characterized by a selective absence of CD8+ T-cells. {ECO:0000269|PubMed:11123350, ECO:0000269|PubMed:11412303, ECO:0000269|PubMed:18509675, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8202713}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Autoimmune disease, multisystem, infantile-onset, 2 (ADMIO2) [MIM:617006]: An autosomal recessive, autoimmune disorder characterized by systemic manifestations including blistering skin disease, uncontrollable bullous pemphigoid, inflammatory colitis, autoimmune hypothyroidism, proteinuria and nephrotic syndrome. {ECO:0000269|PubMed:26783323}. The disease is caused by variants affecting the gene represented in this entry.

DB01238; DB06698; DB05381; DB17087; DB05080; DB00768; DB11642

NA

NA

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

A

34321.1

301

0.16

32.22

9.63

15.11

-7.85