IKZF2

Homo sapiens (Human)

Ikaros family zinc finger protein 2

Ikaros C2H2-type zinc-finger protein family

NA

Associates with Ikaros at centromeric heterochromatin.

Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta (DEE25) [MIM:615905]: An autosomal recessive disease characterized by subclinical seizures appearing in the first days of life, evolving to severe epileptic disease. Affected individuals have profound or severe delayed development with lack of speech, and most patients do not acquire the ability to sit. Additional variable features include axial hypotonia, peripheral hypertonia, and abnormal involuntary movements such as dystonia and choreoathetosis. Dental abnormalities, including delayed eruption, hypodontia, tooth hypoplasia, yellow discoloration, thin enamel, and enamel chipping are observed in most patients. {ECO:0000269|PubMed:24995870, ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523}. The disease is caused by variants affecting the gene represented in this entry.

NA

P29972; P56545; P56545-3; Q17RB8; P09022; Q8N8B7-2

NA

3D-structure; Acetylation; Activator; Alternative splicing; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

B,C

47006.6

410

0.09

44.28

7.23

0.69

-8.18

CHRNA2

Homo sapiens (Human)

NA

NA

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-2/CHRNA2 sub-subfamily

NA

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane."

Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353]: An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. {ECO:0000269|PubMed:16826524}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:25847220}. The disease may be caused by variants affecting the gene represented in this entry.

DB00732; DB00237; DB00411; DB00565; DB01245; DB00514; DB01135; DB07720; DB00898; DB00472; DB00483; DB08960; DB00657; DB01336; DB00416; DB01226; DB00184; DB01337; DB01338; DB00721; DB00728; DB05740; DB00202; DB01199; DB01339

NA

NA

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

A,B,C,D,E

120584

1031

0.14

32.21

5.62

-17.58

-8.17

CRBN

Homo sapiens (Human)

Protein cereblon

CRBN family

NA

Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Intellectual developmental disorder, autosomal recessive 2 (MRT2) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. {ECO:0000269|PubMed:15557513, ECO:0000269|PubMed:28143899}. The disease is caused by variants affecting the gene represented in this entry.

DB00480; DB08910; DB01041

Q96A83-2; P48729; Q16531; O14901; Q8IVT2; Q9P286; A0A6Q8PF08; Q93062; Q16531; Q13422-7

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; Intellectual disability; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc

B,E

38245.7

337

0.08

40.62

5.7

-6.53

-8.16

CHRNA1

Homo sapiens (Human)

NA

ACHRA;CHNRA

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-1/CHRNA1 sub-subfamily

Immune system

Acetylcholine binding.Acetylcholine-gated cation-selective channel activity.Acetylcholine receptor activity.Ion channel activity.Ligand-gated ion channel activity.

Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. {ECO:0000269|PubMed:18252226}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.; DISEASE: Myasthenic syndrome, congenital, 1A, slow-channel (CMS1A) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. {ECO:0000269|PubMed:16685696, ECO:0000269|PubMed:7619526, ECO:0000269|PubMed:8872460, ECO:0000269|PubMed:9158151, ECO:0000269|PubMed:9221765}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 1B, fast-channel (CMS1B) [MIM:608930]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential. {ECO:0000269|PubMed:10195214, ECO:0000269|PubMed:12588888, ECO:0000269|PubMed:15079006}. The disease is caused by variants affecting the gene represented in this entry.

DB08838; DB00565; DB00555

NA

NA

3D-structure; Alternative splicing; Cell membrane; Congenital myasthenic syndrome; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport

A,B,C,D,E

46717.8

411

0.11

38.02

4.77

-22.31

-8.09

HELPY mtnN

Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori)

MTAN; MTA/SAH nucleosidase; Aminofutalosine nucleosidase; Aminodeoxyfutalosine nucleosidase; AFL nucleosidase; 6-amino-6-deoxyfutalosine N-ribosylhydrolase; 5'-methylthioadenosine/S-adenosylhomocystei

PNP/UDP phosphorylase family

NA

Catalyzes the direct conversion of aminodeoxyfutalosine (AFL) into dehypoxanthine futalosine (DHFL) and adenine via the hydrolysis of the N-glycosidic bond; this reaction seems to represent an essential step in the menaquinone biosynthesis pathway in Helicobacter species. Can also probably catalyzes the hydrolysis of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. These other activities highlight the tremendous versatility of the enzyme, which also plays key roles in S-adenosylmethionine recycling and in the biosynthesis of the quorum-sensing molecule autoinducer-2. Does not act on futalosine (FL) as substrate.

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.

NA

NA

NA

3D-structure; Amino-acid biosynthesis; Hydrolase; Menaquinone biosynthesis; Methionine biosynthesis; Reference proteome

A,B

50547.6

464

0.08

26.92

5.13

-20.92

-8.07

cumD

Pseudomonas fluorescens

NA

NA

NA

Hydrolase

Hydrolase activity.

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

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

NA

NA

3D-structure; Hydrolase

A

30307.9

271

0.1

37.49

5.02

-11.58

-8.07

LTA4H

Homo sapiens (Human)

Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase

Peptidase M1 family

Ether bond hydrolase

Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4.

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.

DB07102; DB06917; DB07258; DB07094; DB07259; DB02352; DB07292; DB07104; DB06828; DB08466; DB01197; DB05177; DB03366; DB08040; DB06851; DB02062; DB07099; DB07260; DB07196; DB11781; DB03424; DB07237

Q9BSI4

EC 3.3.2.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Hydrolase; Leukotriene biosynthesis; Lipid metabolism; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Zinc

A

68927

608

0.1

38.84

5.87

-9.86

-8

Pseudo LasR

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

Autoinducer-regulated transcriptional regulatory protein family

NA

Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

DB08324

NA

NA

3D-structure; Activator; DNA-binding; Quorum sensing; Reference proteome; Transcription; Transcription regulation

A

18305.5

163

0.12

46.52

5.19

-6.78

-8.01

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

-7.99

mmaA2

Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

NA

Rv0644c;mma2

CFA/CMAS family

Transferase

Cyclopropane-fatty-acyl-phospholipid synthase activity.Methyltransferase activity.

Oocyte/zygote/embryo maturation arrest 16 (OZEMA16) [MIM:617234]: A rare cause of female primary infertility. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27545678}. The disease is caused by variants affecting the gene represented in this entry.

DB01718; DB01752

NA

2.1.1.79

3D-structure; Acetylation; Lipid biosynthesis; Lipid metabolism; Methyltransferase; Reference proteome; S-adenosyl-L-methionine; Transferase

A

32493.6

285

0.1

43.61

5.53

-10.17

-7.99

HDAC2

Homo sapiens (Human)

HD2

Histone deacetylase family, HD type 1 subfamily

Carbon-nitrogen hydrolase

Gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. 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. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Ventricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy (CPVT1) [MIM:604772]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT1 inheritance is autosomal dominant. {ECO:0000269|PubMed:11157710, ECO:0000269|PubMed:11159936, ECO:0000269|PubMed:11208676, ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:12106942, ECO:0000269|PubMed:14571276, ECO:0000269|PubMed:15046072, ECO:0000269|PubMed:15046073, ECO:0000269|PubMed:15466642, ECO:0000269|PubMed:15544015, ECO:0000269|PubMed:16188589, ECO:0000269|PubMed:24793461, ECO:0000269|PubMed:25372681, ECO:0000269|PubMed:27733687}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome (VACRDS) [MIM:115000]: An autosomal dominant arrhythmogenic disorder characterized by syncope, cardiac arrest and/or sudden unexpected death, often in association with physical exertion or acute emotional stress. Patients who survive manifest polymorphic ventricular tachycardia and ventricular fibrillation. Unlike typical catecholaminergic ventricular tachycardia, arrhythmias are not reproducible on exercise stress testing or adrenaline challenge. {ECO:0000269|PubMed:12093772, ECO:0000269|PubMed:17984046, ECO:0000269|PubMed:33536282}. The disease is caused by variants affecting the gene represented in this entry.

DB12565; DB01223; DB01076; DB05015; DB01262; DB11841; DB01095; DB12645; DB00227; DB11830; DB01303; DB06603; DB06819; DB05223; DB00175; DB03766; DB12847; DB06176; DB00641; DB00277; DB09091; DB00313; DB02546

Q9C0K0; Q9HCU9; P68400; Q9UER7; P51610; Q13547; Q9UIS9; Q13330; P01106; P06748; P48382; Q96ST3; O95863; Q9HD15; O43463; Q9H3M7; Q92618; Q17R98; Q2HR82; PRO_0000449623 [P0DTD1]

EC 3.5.1.98

3D-structure; Acetylation; Alternative splicing; Biological rhythms; Chromatin regulator; Cytoplasm; Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation

A,B,C

42020.5

366

0.13

29.52

6.52

-2.16

-7.99

CHRNA2

Homo sapiens (Human)

CHRNA2

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-2/CHRNA2 sub-subfamily

Neurotransmitter receptor

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353]: An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. {ECO:0000269|PubMed:16826524}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:25847220}. The disease may be caused by variants affecting the gene represented in this entry.

DB00732; DB00237; DB00411; DB00565; DB01245; DB00514; DB01135; DB07720; DB00898; DB00472; DB00483; DB08960; DB00657; DB01336; DB00416; DB01226; DB00184; DB01337; DB01338; DB00721; DB00728; DB05740; DB00202; DB01199; DB01339

NA

NA

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

A,B

48323.4

413

0.15

32

5.69

-6.58

-7.98

PTPN11

Homo sapiens (Human)

Tyrosine-protein phosphatase non-receptor type 11; SHPTP2; SHP2; SHP-2; SH-PTP3; SH-PTP2; Protein-tyrosine phosphatase SHP2; Protein-tyrosine phosphatase 2C; Protein-tyrosine phosphatase 1D; PTP2C; PT

Protein-tyrosine phosphatase family, Non-receptor class 2 subfamily

Phosphoric monoester hydrolase

Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73. Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

LEOPARD syndrome 1 (LPRD1) [MIM:151100]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:12058348, ECO:0000269|PubMed:14961557, ECO:0000269|PubMed:15121796, ECO:0000269|PubMed:15389709, ECO:0000269|PubMed:15520399, ECO:0000269|PubMed:15690106, ECO:0000269|PubMed:16679933, ECO:0000269|PubMed:16733669, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:26742426}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 1 (NS1) [MIM:163950]: 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. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints. {ECO:0000269|PubMed:11704759, ECO:0000269|PubMed:11992261, ECO:0000269|PubMed:12161469, ECO:0000269|PubMed:12325025, ECO:0000269|PubMed:12529711, ECO:0000269|PubMed:12634870, ECO:0000269|PubMed:12717436, ECO:0000269|PubMed:12739139, ECO:0000269|PubMed:12960218, ECO:0000269|PubMed:15384080, ECO:0000269|PubMed:15889278, ECO:0000269|PubMed:15948193, ECO:0000269|PubMed:19020799, ECO:0000269|PubMed:24891296, ECO:0000269|PubMed:28074573}. The disease is caused by variants affecting the gene represented in this entry. Mutations in PTPN11 account for more than 50% of the cases.; DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. {ECO:0000269|PubMed:12717436, ECO:0000269|PubMed:26742426}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Metachondromatosis (MC) [MIM:156250]: A skeletal disorder with radiologic features of both multiple exostoses and Ollier disease, characterized by the presence of exostoses, commonly of the bones of the hands and feet, and enchondromas of the metaphyses of long bones and iliac crest. {ECO:0000269|PubMed:20577567}. The disease is caused by variants affecting the gene represented in this entry.

DB02779

P10275; P32239; Q9BZW8; P20138; Q08345; P00533; P29317; P04626; Q8WU20; Q13480; Q9UQC2; P62993; P08069; P06213; P35568; P43628; P10721; P08581; O95297; Q15116; P09619; P16284; P49023; P49247; Q13049; P68105; Q71V39; P35570; P97710; Q6P1J9; Q13480; O75496; Q9UKI8

EC 3.1.3.48

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Deafness; Disease variant; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase; Proteomics identification; Reference proteome; Repeat; SH2 domain

A

56341.2

491

0.09

41.37

7.76

2.43

-7.96

CASP6

Homo sapiens (Human)

MCH2; Caspase-6 subunit p18; Caspase-6 subunit p11; CASP-6; Apoptotic protease Mch-2

Peptidase C14A family

Peptidase

Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9Y614; Q6DHV7-2; Q6UY14-3; Q96MA6; Q5T2L2; Q96Q83-2; Q9Y303-2; Q9NU02; P09525; P06727; Q8WW27; Q66PJ3-4; Q6XD76; P18848; Q9H0Y0; Q14032; P54687-4; P06276; Q9NSI6-4; Q96Q07-2; Q9H0W9-3; Q9NQ89; Q13901; Q3SXR2; Q8N1A6; P17655; P20807-4; P42574; P55212; O00257-3; P24863; Q9NNX6-10; Q9UJX2; P42773; O95674; Q494V2-2; Q8WUX9; Q9Y3D0; Q8N365; Q3SX64; Q99966; P09496-2; Q6PJW8-3; Q96BR5; P02458-1; Q9UGL9; Q9UKG9-2; P26998; P35222; Q53TN4; P61962; O60479; Q96EY1-3; Q92782-2; Q9BPU6; A0AVK6; Q658K8; O00303; Q13347; O00472; O00423; Q6NXG1-3; Q49AJ0-4; Q8N128-2; Q8IZU1; Q6ZNL6; Q9NSA1; Q06547-3; Q49A26-4; Q9HAV0; Q6NXT2; Q9BT25; Q9NRZ9-6; Q96EW2-2; P42858; Q8N6M8-2; Q92613; P0C870; Q9UK76; Q8N5Z5; Q8TBB5-2; Q9UH77; Q8N4N3-2; Q5JUW0-3; Q8N1A0; P13473-2; Q6DKI2; Q9H2C1; Q8N0U6; Q9Y234; Q8TBB1; Q1L5Z9; Q96JB6; Q16609; Q8IYG6; P0DP58-2; Q969L2; P27338; A6NJ78-4; Q96C03-3; Q8N5J2-3; A0A0A0MR05; P34949-2; Q9BV20; Q6IN84-2; A2RUH7; P01106; Q9H7X0; Q15742-2; Q9UJ70-2; Q8NDH3-5; Q96HA8; P36639-4; Q8NFH4; Q8NFH3; Q7Z3B4; Q6N063-2; Q6GQQ9-2; Q9H8K7; Q99447; P27815-4; O15534; Q9BUL5; Q00169; P48739; P61925; Q58EX7-2; O60664; Q14181; P0DPB6; P36954; Q07869; O60927; Q6ZMI0-5; P54619; Q8NCQ7-2; P41222; P29074; Q8WUD1-2; Q5R372-9; Q9HD47-3; Q09028; Q04206; P47804-3; Q15382; Q06587; Q8N5U6; P62701; Q66K80; Q01826; O15126; P22307-3; Q9BRK5; Q9NTN9-3; P01011; Q15393; Q9NR46; Q9BZQ2; O60902-3; Q86US8; P37840; Q96H20; Q13573; Q7Z6I5; Q496A3; Q9C004; Q5W111-2; Q96BD6; Q92797-2; O60506-4; O15273; Q86WV5; Q96A09; P54274-2; P22735; O43548; Q9NQ88; Q9UIK5-2; Q53NU3; P04637; Q12888; P36406; Q86WT6-2; Q13885; P49459; Q9P1Q0-4; Q9NX94; Q8NA23-2; Q9BQA1; O00755; O95070; O43829; Q8IWT0-2; Q53FD0-2; Q05CR2; Q96JL9-2; Q96LX8; Q3KNS6-3; Q5JTY5; A0A384MDV8; B7Z3E8; Q86V28

EC 3.4.22.59

3D-structure; Alternative splicing; Apoptosis; Autocatalytic cleavage; Cytoplasm; Hydrolase; Lipoprotein; Nucleus; Palmitate; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Zymogen

A,B

57170

500

0.12

31.33

8.05

4.52

-7.96

GPR119

Homo sapiens (Human)

GPR119; G-protein coupled receptor 119

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.

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.

DB05166

Q12797-6

NA

3D-structure; Cell membrane; G-protein coupled receptor; Lipid-binding; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

32134.1

292

0.12

34.96

9.12

8.03

-7.95

PFF0160c

Plasmodium falciparum (isolate 3D7)

NA

NA

Dihydroorotate dehydrogenase family, Type 2 subfamily

Oxidoreductase

Dihydroorotate dehydrogenase activity.

Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. The disease is caused by variants affecting the gene represented in this entry.

DB01117

NA

1.3.5.2

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

A,B

42573.5

378

0.1

36.63

8.21

3.17

-7.93

ATIC

Homo sapiens (Human)

PURH; OK/SW-cl.86; Bifunctional purine biosynthesis protein PURH

PurH family

Methyltransferase

Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.

AICA-ribosuria due to ATIC deficiency (AICAR) [MIM:608688]: A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. Clinical features include profound intellectual disability, epilepsy, dysmorphic features and congenital blindness. AICAR inheritance is autosomal recessive. {ECO:0000269|PubMed:15114530}. The disease is caused by variants affecting the gene represented in this entry.

DB02309; DB03442; DB01700; DB01972; DB00563; DB04057; DB00642; DB00116

NA

NA

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Disease variant; Epilepsy; Hydrolase; Intellectual disability; Multifunctional enzyme; Proteomics identification; Purine biosynthesis; Reference proteome; Transferase

A,B

128556

1177

0.07

38.21

6.28

-7.98

-7.93

TK1

Homo sapiens (Human)

Thymidine kinase, cytosolic

Thymidine kinase family

Kinase

cytosol, identical protein binding, thymidine kinase activity, zinc ion binding, DNA metabolic process, nucleobase-containing compound metabolic process, protein homotetramerization, pyrimidine nucleoside salvage, thymidine metabolic process

Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 11 (DEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy. {ECO:0000269|PubMed:29635106}.; DISEASE: Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD. {ECO:0000269|PubMed:28256214}.; DISEASE: Episodic ataxia 9 (EA9) [MIM:618924]: An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. {ECO:0000269|PubMed:26645390, ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27328862, ECO:0000269|PubMed:28065826}. The disease is caused by variants affecting the gene represented in this entry.

DB01692; DB04485; DB02452; DB00432; DB00495

P05067; A0A087WZT3; Q92993; Q1RN33; P04183

EC 2.7.1.21

3D-structure; Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Ubl conjugation; Zinc

A

19373.5

174

0.09

36.21

8.63

3.88

-7.93

DPP9

Homo sapiens (Human)

Dipeptidyl peptidase-like protein 9; Dipeptidyl peptidase IX; Dipeptidyl peptidase IV-related protein 2; DPRP2; DPRP-2; DPP IX; DPLP9; DP9

Peptidase S9B family, DPPIV subfamily

Peptidase

Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

Hatipoglu immunodeficiency syndrome (HATIS) [MIM:620331]: An autosomal recessive immunologic disorder manifesting in infancy or early childhood, and characterized by failure to thrive, short stature, skin pigmentation abnormalities, pancytopenia, and susceptibility to recurrent infections. {ECO:0000269|PubMed:36112693}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NXR5; Q86TI2; Q6NUP5; P46379-2; Q8WUW1; Q96A83-2; O75190-2; O14645; Q01658; P29692-2; Q06787-7; Q9Y5Q9; O14901; Q9BVL2; Q96CV9; Q06830; P14678-2; P49458; Q11203; Q13148; P14927

EC 3.4.14.5

3D-structure; Acetylation; Alternative splicing; Aminopeptidase; Cytoplasm; Disease variant; Hydrolase; Nucleus; Protease; Proteomics identification; Reference proteome; Serine protease

A

92797.4

808

0.12

37.45

6.34

-8.98

-7.92

GABBR1

Homo sapiens (Human)

NA

GPRC3B;GPR51

G-protein coupled receptor 3 family, GABA-B receptor subfamily

Signaling protein / antagonist

G-protein coupled GABA receptor activity.

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.

DB08891; DB08892; DB00181; DB00363; DB02530; DB05010; DB09072

Q9UBS5; Q9UBS5-2; P46459; Q86UR5

NA

3D-structure; Cell membrane; Coiled coil; Direct protein sequencing; Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; Intellectual disability; Membrane; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transducer; Transmembrane; Transmembrane helix

A

46502.1

408

0.12

50.05

5.78

-5.62

-7.91