ALOX5AP

Homo sapiens (Human)

MK-886-binding protein; FLAP; ALOX5AP

MAPEG family

NA

Required for leukotrienebiosynthesis by ALOX5 (5- lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.

Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (PubMed:14770184), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (PubMed:17304054) ALOX5AP is not implicated in this condition. {ECO:0000269|PubMed:14770184, ECO:0000269|PubMed:17304054}.

DB05225; DB04929; DB06346; DB16739; DB16346

Q13520; O15552; O15529; Q9H115; P35372-10; A0PK00; Q96FB2

NA

3D-structure; Endoplasmic reticulum; Leukotriene biosynthesis; Membrane; Nucleus; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A,C

32584.3

288

0.17

23.55

8.82

3.82

-8.86

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

-8.84

SLC5A2

Homo sapiens (Human)

Solute carrier family 5 member 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter

Sodium:solute symporter (SSF) (TC 2.A.21) family

Solute:sodium symporter

Has a Na(+) to glucose coupling ratio of 1:1. Sodium-dependent glucose transporter.

Renal glucosuria (GLYS) [MIM:233100]: A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction. {ECO:0000269|PubMed:14614622}. The disease is caused by variants affecting the gene represented in this entry.

DB12236; DB08907; DB01914; DB06292; DB09038; DB11827; DB12713

O14556; Q13113

NA

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Ion transport; Membrane; Metal-binding; Proteomics identification; Reference proteome; Sodium; Sodium transport; Sugar transport; Symport; Transmembrane; Transmembrane helix; Transport

A

63858.9

586

0.12

39.46

8.62

7.41

-8.84

Fung SDH1

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

SDH1

Scytalone dehydratase family

Alpha-carbonic anhydrase

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

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

NA

NA

EC 4.2.1.94

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

A

19102.4

162

0.14

31.72

5.87

-3.7

-8.84

Malaria Adss

Plasmodium falciparum

IMP--aspartate ligase; Adenylosuccinate synthase; AdSS; AMPSase

Adenylosuccinate synthetase family

Carbon-nitrogen ligase

Plays an important role in the salvage pathway for purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.

Hypertension and brachydactyly syndrome (HTNB) [MIM:112410]: A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. {ECO:0000269|PubMed:25961942}. The disease is caused by variants affecting the gene represented in this entry.

DB03510; DB04315; DB02109

NA

EC 6.3.4.4

3D-structure; Cytoplasm; GTP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding; Purine biosynthesis

A

47877.9

424

0.09

31.72

7.63

1.58

-8.84

THRA

Homo sapiens (Human)

V-erbA-related protein 7; THRA2; THRA1; Nuclear receptor subfamily 1 group A member 1; NR1A1; ERBA1; EAR7; EAR-7; C-erbA-alpha; C-erbA-1

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription.

Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) [MIM:614450]: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance. {ECO:0000269|PubMed:22168587, ECO:0000269|PubMed:24969835, ECO:0000269|PubMed:25670821, ECO:0000269|PubMed:26037512}. The disease is caused by variants affecting the gene represented in this entry.

DB01118; DB00509; DB04855; DB05035; DB03176; DB00451; DB00279; DB01583; DB05235; DB09100

Q9Y2J4; Q9Y2J4-4; O95971; Q8TAP6; Q96JM7; Q15648; Q6FHY5; P31321; Q96A49; O75410-7; Q9JLI4

NA

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

A

29910.1

267

0.07

52.75

5.31

-11.32

-8.82

BBOX1

Homo sapiens (Human)

NA

BBH;BBOX

Gamma-BBH/TMLD family

Oxidoreductase

Gamma-butyrobetaine dioxygenase activity.Identical protein binding.Iron ion binding.Zinc ion binding.

Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS) [MIM:617903]: An autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability. {ECO:0000269|PubMed:26740508, ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 59 (DEE59) [MIM:617904]: 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. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy. {ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29100083, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.

DB00126

O75936; A0MZ66-7

1.14.11.1

3D-structure; Carnitine biosynthesis; Cytoplasm; Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

31642.5

275

0.12

35.68

6.33

-2.46

-8.83

GSR

Homo sapiens (Human)

Glutathione reductase, mitochondrial; GRase; GRD1; GLUR

Class-I pyridine nucleotide-disulfide oxidoreductase family

Sulfur donor oxidoreductase

Maintains high levels of reduced glutathione in the cytosol.

Hemolytic anemia due to glutathione reductase deficiency (HAGRD) [MIM:618660]: An autosomal recessive disease characterized by hemolytic anemia and impaired activity of glutathione reductase. Patients experience hemolytic anemia in response to oxidative stress or ingestion of fava beans. {ECO:0000269|PubMed:17185460}. The disease is caused by variants affecting the gene represented in this entry.

DB07393; DB01644; DB02895; DB03867; DB02153; DB07714; DB09061; DB00262; DB09130; DB03147; DB00143; DB03310; DB02553; DB14009; DB14011; DB00157; DB11135; DB11590

NA

EC 1.8.1.7

3D-structure; Acetylation; Alternative initiation; Alternative splicing; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; FAD; Flavoprotein; Hereditary hemolytic anemia; Mitochondrion; NADP; Oxidoreductase; Proteomics identification; Redox-active center; Reference proteome; Transit peptide

A

49983.1

462

0.06

38.04

7.73

2.16

-8.82

N/A

Clostridium pasteurianum

NA

NA

NA

Oxidoreductase

4 iron, 4 sulfur cluster binding.Electron carrier activity.Ferredoxin hydrogenase activity.Iron ion binding.

Noonan syndrome 13 (NS13) [MIM:619087]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity. {ECO:0000269|PubMed:32721402}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

1.12.7.2

3D-structure; 4Fe-4S; Direct protein sequencing; Iron; Iron-sulfur; Metal-binding; Oxidoreductase; Repeat

A

47536.9

430

0.08

33.26

6.52

-1.83

-8.83

RXRB

Homo sapiens (Human)

Retinoid X receptor beta; Nuclear receptor subfamily 2 group B member 2; NR2B2

Nuclear hormone receptor family, NR2 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 RAR/RXR heterodimers bind to the retinoic acid response elements (RARE). Receptor for retinoic acid.

Noonan syndrome 13 (NS13) [MIM:619087]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity. {ECO:0000269|PubMed:32721402}. The disease is caused by variants affecting the gene represented in this entry.

DB08175; DB00459; DB00210; DB00523; DB00307; DB01393; DB03756; DB00926; DB01941; DB07929; DB02746; DB00412; DB00799; DB07080; DB00755

Q00975; Q9HB07; F1D8P7; Q13133; Q13133-3; Q96RI1-1; P04150; Q9NRD5; P37231; P10276; P10276-2; P10826-2; P13631; Q6IQ16; Q13137; Q96B26; Q08379; Q6A162; Q9UJV3-2; Q13133-3; Q96RI1-1; O43586; P10276; P10826-2; Q8IUQ4-2; O75528; Q12800; Q9UBB9; Q05BL1; P14373; O94972; Q96S82

NA

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

A,C

28845.8

251

0.08

54.86

6.74

-0.6

-8.82

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

-8.83

SEC14L3

Homo sapiens (Human)

NA

TAP2

NA

Transport protein

Lipid binding.Transporter activity.

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM) [MIM:300863]: A disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild intellectual disability. {ECO:0000269|PubMed:20181727}. The disease is caused by variants affecting the gene represented in this entry.

DB14003; DB14001; DB14002; DB11635; DB11251; DB00163

NA

NA

3D-structure; Alternative splicing; Lipid-binding; Proteomics identification; Reference proteome; Transport

A

46148.7

401

0.1

45.19

5.79

-5.94

-8.83

LIMK2

Homo sapiens (Human)

LIMK-2; LIM domain kinase 2

Protein kinase superfamily, TKL Ser/Thr protein kinase family

Kinase

Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro.

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (MRT80) [MIM:620653]: An autosomal recessive disorder characterized by global developmental delay, mildly to moderately impaired intellectual development, attention deficit-hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. Brain imaging shows fronto-temporal lissencephaly and pachygyria. {ECO:0000269|PubMed:37880421}. The disease is caused by variants affecting the gene represented in this entry.

DB11718; DB12010

Q16543; P08238; Q96C90; P62258

EC 2.7.11.1

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Cytoskeleton; Kinase; LIM domain; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc

A

32109.2

283

0.1

27.28

6.01

-3.93

-8.82

ESRRA

Homo sapiens (Human)

Nuclear receptor subfamily 3 group B member 1; NR3B1; Estrogen-relatedreceptor, alpha; Estrogen-relatedreceptor alpha; Estrogen-related receptor alpha; Estrogen receptor-like 1; ESRL1; ERRalpha; ERR1;

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle. Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'.

Intellectual developmental disorder, autosomal recessive 54 (MRT54) [MIM:617028]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity. {ECO:0000269|PubMed:27106596}. The disease may be caused by variants affecting the gene represented in this entry.

DB06833; DB04468; DB06732; DB00255; DB07776; DB01645; DB00197

P62508-3; Q8IZU1; Q16665; Q8N2W9; Q9UBK2; Q04864-2; P78317; P48788

NA

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

24086.8

218

0.06

53.27

4.95

-10.74

-8.83

KIT

Homo sapiens (Human)

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; p145 c-kit; Proto-oncogene tyrosine-protein kinase Kit; Proto-oncogene c-Kit; Piebald trait protein; PBT; Mast/stem cell growth factor re

Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily

Kinase

In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis.

Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. {ECO:0000269|PubMed:11074500, ECO:0000269|PubMed:1370874, ECO:0000269|PubMed:1376329, ECO:0000269|PubMed:1717985, ECO:0000269|PubMed:7687267, ECO:0000269|PubMed:8680409, ECO:0000269|PubMed:9450866, ECO:0000269|PubMed:9699740}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741, ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.; DISEASE: Mastocytosis, cutaneous (MASTC) [MIM:154800]: A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign. {ECO:0000269|PubMed:15173254, ECO:0000269|PubMed:19865100, ECO:0000269|PubMed:21689725, ECO:0000269|PubMed:24289326, ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mastocytosis, systemic (MASTSYS) [MIM:154800]: A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality. {ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.

DB12742; DB09103; DB15233; DB01254; DB12147; DB12010; DB00619; DB09078; DB06080; DB06595; DB04868; DB05913; DB06589; DB12978; DB01962; DB08901; DB08896; DB14840; DB00398; DB01268; DB11800; DB05146

P00519; P42684; O75815; P51451; Q8WV28; P46108; P07332; P09769; O75791; P62993; Q14451; P08631; Q96JZ2; P21583; P06239; P07948; P16333; O43639; P27986; O00459; Q92569; P19174; P16885; Q13882; Q06124; Q92729; P20936; Q9UQQ2; O14796; Q9NP31; Q8N5H7; P78314; Q15464; P29353; P98077; Q92529; Q9H6Q3; O14508; O14543; O14544; P12931; Q9ULZ2; Q9HBL0; Q63HR2; Q68CZ2; P42681; P07947; P43403; Q8VBX6; P35235

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

33575.6

297

0.11

45.37

8.37

3.24

-8.81

HBA1

Homo sapiens (Human)

NA

HBA2

Globin family

Oxygen storage / transport

Heme binding.Iron ion binding.Oxygen binding.Oxygen transporter activity.

Heinz body anemias (HEIBAN) [MIM:140700]: Form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency. {ECO:0000269|PubMed:2833478}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Alpha-thalassemia (A-THAL) [MIM:604131]: A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Alpha(0)-thalassemia is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.; DISEASE: Hemoglobin H disease (HBH) [MIM:613978]: A form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence. {ECO:0000269|PubMed:10569720}. The disease is caused by variants affecting the gene represented in this entry.

DB08262; DB07427; DB08077; DB07428; DB02126; DB09130; DB08486; DB15617; DB09147; DB13995; DB14490; DB14491; DB14488; DB14501; DB14489; DB13257; DB01592; DB00893; DB09112; DB09140; DB06154; DB07645; DB09517; DB08632; DB14975; DB01593; DB14487; DB14533; DB14548

Q9NZD4; Q2TAC2; P00387; P68871; P02042; P02100; P69892; P09105; Q15323; O76011; Q6A162; P29474; P0DPK4

NA

3D-structure; Acetylation; Direct protein sequencing; Disease variant; Glycation; Glycoprotein; Heme; Hereditary hemolytic anemia; Iron; Metal-binding; Oxygen transport; Phosphoprotein; Proteomics identification; Reference proteome; Transport

A

30975.2

287

0.08

6.57

7.92

2.38

-8.81

KDM1A

Homo sapiens (Human)

Lysine-specific histone demethylase 1A; LSD1; KIAA0601; KDM1; Flavin-containing amine oxidase domain-containing protein 2; BRAF35-HDAC complex protein BHC110; AOF2

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.

Cleft palate, psychomotor retardation, and distinctive facial features (CPRF) [MIM:616728]: A syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion. {ECO:0000269|PubMed:23020937, ECO:0000269|PubMed:24838796, ECO:0000269|PubMed:26656649}. The disease is caused by variants affecting the gene represented in this entry.

DB16446

Q9BYF1; Q99996; Q86SG2; Q13490; Q6P047; Q8TC20-4; Q9BWT7; Q49A88-3; Q99459; Q9BXL8; Q86XR8-3; Q8NHQ1; Q8TAP6; Q12873; P38432; Q96EY1; P26378-2; Q9UPT5-1; Q3B820; Q9H8W3; Q8IZU1; Q9BQS8; O95995; Q96CN9; Q08379; Q9NYA3; Q8NEC7; Q9BX10; Q16695; Q96CS2; O15379; Q9UBX0; Q9NSC5; Q16891; O75564-2; O60341; Q9BVG8-5; Q8TBB5; P19012; Q15323; Q14525; Q92764; Q6A163; Q6A162; Q96JB6; Q9Y250; O95983; P01106; Q3BBV0; Q7Z6G3-2; P35240; Q16236; P46531; Q13133; Q9Y466; Q96F24; A5D8V7; Q8IZS5; Q9BYU1; Q8IZL8; Q99471; Q5T6S3; Q03181; P62191; Q9NS23; P50749; Q86WH2; Q06330; Q9UKL0; Q8IZ40; Q9P2K3-2; Q96P16-3; Q8N6K7; Q9UGK8; Q13435; O15198; O95863; Q96H20; Q8N0Z3; Q96BD6; Q8N4C7; Q8N6V9; Q9UBB9; Q08117-2; Q2M3C6; P45379-11; Q05BL1; Q9BUZ4; Q5W5X9-3; Q8TF42; Q9H9H4; Q9Y3C0; O96006; O15060; Q92618; O14646; Q96KQ7; Q96KQ7-1; P05771-1; Q9UKL0; P17542; P04637; P22091

EC 1.-.-.-

3D-structure; Acetylation; Alternative splicing; Chromatin regulator; Chromosome; Coiled coil; Developmental protein; Direct protein sequencing; Disease variant; FAD; Flavoprotein; Isopeptide bond; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation

A

72462.2

651

0.08

32.07

7.01

0.05

-8.81

EBP

Homo sapiens (Human)

Emopamilbinding protein; EBP; Delta(8)Delta(7) sterol isomerase; D8D7 sterol isomerase; 3betahydroxysteroidDelta(8),Delta(7)isomerase

EBP family

Intramolecular oxidoreductases

Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.

Chondrodysplasia punctata 2, X-linked dominant (CDPX2) [MIM:302960]: A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)-en-3-beta-ol in the plasma and tissues. {ECO:0000269|PubMed:10391218, ECO:0000269|PubMed:10391219, ECO:0000269|PubMed:10942423, ECO:0000269|PubMed:11493318, ECO:0000269|PubMed:18176751, ECO:0000269|PubMed:25814754}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: MEND syndrome (MEND) [MIM:300960]: An X-linked recessive disorder associated with a defect in sterol biosynthesis. Disease manifestations and severity are highly variable. Clinical features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. {ECO:0000269|PubMed:12503101, ECO:0000269|PubMed:20949533, ECO:0000269|PubMed:24459067, ECO:0000269|PubMed:24700572}. The disease is caused by variants affecting the gene represented in this entry.

DB00675

O95870; Q86W74-2; Q13520; Q3SXY8; Q8N6S5; Q9H2C2; Q9HD20-3; O95393; Q12983; Q8WVV5; P06681; O14523; Q8WVX3-2; P01031; Q6UWT4; Q9P0B6; Q8NHW4; P25942; Q07108; P60033; O14735; P23141-3; Q9H9P2; Q8NHS1; O43889-2; Q96BA8; P49447; O43169; P78329; P81534; Q9H1M4; Q96LL9; Q15125; Q08426; Q9BV81; P54849; Q9UKR5; Q9Y282; Q7L5A8; Q5JX71; Q96IV6; Q9UGM5; Q9Y3D6; Q14318; Q9BWH2; Q14802-3; Q9H0Q3; Q8WWP7; Q96F15; P29033; O95452; O14653; Q8TDT2; P02724; P30519; Q7Z5P4; Q9Y5U9; Q9Y5U4; Q8N5M9; Q5T700; Q68G75; Q7L5N7; Q7Z4F1; Q96AG4; Q16873; Q6ZSS7; P50281; Q5J8X5; Q9UHE5; O95167; Q9NX14; Q99519; Q92982; Q9NZG7; Q16617; Q8IXM6; Q2M2E3; Q9P0S3; Q53FV1; Q8N138; Q7RTS5; Q9Y342; Q04941; Q8IY26; Q01453; P54315; P43378; P15151; Q8N8N0; Q5QGT7; Q96GQ5; Q9NTJ5; Q969E2; O75396; Q9Y6X1; Q8N6R1; Q9BWM7; Q8TD22; Q8IWU4; Q96G79; Q2M3R5; Q9NVC3; P08195-4; Q96JW4; Q6P1K1; Q0VAQ4; Q9NRQ5; B2RUZ4; Q9BZL3; Q6UX34; Q86Y82; P61266; Q13190; O43752; O15400; Q9UNK0; O43759-2; P57105; Q8N2H4; Q96BZ9; P07204; O14925; Q96CP7; Q96MV1; P55061; Q9NV29; P17152; Q9BXJ8; A0PK00; Q9NV12; Q9BVK8; Q9NUH8; Q9P0S9; Q9NRX6; Q8N511; Q969S6; Q9BTX3; A2RU14; Q9H0R3; Q8NBD8; Q8WW34-2; Q9NWH2; Q9BU79; Q8TBM7; Q69YG0; Q9NW97; Q9H2L4; Q6PI78; Q8N2M4; Q8N661; Q5BJF2; Q9NSU2-1; A0AVG3; Q5TGU0; A5PKU2; Q9Y385; Q9Y5Z9; Q53HI1; Q9H1C4; Q9NZ43; P23763-3; P63027; Q15836; O75379; Q9P0L0; O95292; O95070; Q9Y548; Q9BSR8; Q96EC8; Q6UX98; O95159

EC 5.3.3.5

3D-structure; Acetylation; Cataract; Cholesterol biosynthesis; Cholesterol metabolism; Cytoplasmic vesicle; Disease variant; Dwarfism; Endoplasmic reticulum; Ichthyosis; Isomerase; Lipid biosynthesis; Lipid metabolism; Membrane; Nucleus; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix

A

24012.7

206

0.17

42.52

6.19

-3.19

-8.81

GRIN2A

Homo sapiens (Human)

NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A

Glutamate-gated ion channel (TC 1.A.10.1) family, NR1/GRIN1 subfamily

Glutamate-gated ion channel

Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 101 (DEE101) [MIM:619814]: 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. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:34611970}. The disease is caused by variants affecting the gene represented in this entry.

DB01931; DB00659; DB06151; DB08838; DB01238; DB00289; DB05824; DB04620; DB03929; DB00647; DB00843; DB00228; DB11823; DB13146; DB06741; DB00142; DB00874; DB08954; DB06738; DB09409; DB09481; DB01043; DB00454; DB00333; DB04896; DB01173; DB00312; DB01174; DB01708; DB00418; DB00193

P05067; P35637; Q12879-1; Q13224; Q62936

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Intellectual disability; Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc

B

63014.6

557

0.1

28.81

8.59

7.66

-8.8

MME

Homo sapiens (Human)

Skin fibroblast elastase; SFE; Neutral endopeptidase 24.11; Neprilysin; NEP protein; Enkephalinase; EPN; Common acute lymphocytic leukemia antigen; CD10; CALLA; Atriopeptidase

Peptidase M13 family

Peptidase

Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers. Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids.

Charcot-Marie-Tooth disease, axonal, 2T (CMT2T) [MIM:617017]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:26991897, ECO:0000269|PubMed:27588448}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:27583304}. The disease is caused by variants affecting the gene represented in this entry.

DB08575; DB02597; DB00616; DB11623; DB05796; DB06655; DB02558; DB02062; DB00886; DB02557; DB09292; DB13928; DB08626

P05067; P21926; Q06787-7; P08107; P04792

EC 3.4.24.11

3D-structure; Cell membrane; Charcot-Marie-Tooth disease; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Lipoprotein; Membrane; Metal-binding; Metalloprotease; Myristate; Neurodegeneration; Neuropathy; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Spinocerebellar ataxia; Transmembrane; Transmembrane helix; Zinc

A

79435.8

696

0.11

37.5

5.53

-11.46

-8.79