NT5E

Homo sapiens (Human)

NT5; CD73 antigen; 5'-nucleotidase; 5'-NT

5'-nucleotidase family

Phosphoric monoester hydrolase

Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Hydrolyzes extracellular nucleotides into membrane permeable nucleosides.

Calcification of joints and arteries (CALJA) [MIM:211800]: A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. {ECO:0000269|PubMed:21288095, ECO:0000269|PubMed:24887587}. The disease is caused by variants affecting the gene represented in this entry.

DB00987; DB00806

Q9Y225-2; Q8WWF5

EC 3.1.3.5

3D-structure; Alternative splicing; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding; Nucleotide-binding; Proteomics identification; Reference proteome; Signal; Zinc

A

24417.6

219

0.09

40.43

5.49

-5.75

-5.55

KDM2A

Homo sapiens (Human)

FBXL11; FBL7; F-box/LRR-repeat protein 11; F-box protein Lilina; F-box protein FBL7; F-box and leucine-rich repeat protein 11; CXXC8; CXXC-type zinc finger protein 8; [Histone-H3]-lysine-36 demethylas

JHDM1 histone demethylase family

NA

Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer and RORA in a catalytically-independent manner.

Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. {ECO:0000269|PubMed:10718838, ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800, ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320, ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368, ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313, ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837, ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434, ECO:0000269|PubMed:9843052}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q04206; P63208

EC 1.14.11.27

3D-structure; ADP-ribosylation; Alternative splicing; Biological rhythms; Chromatin regulator; Chromosome; Dioxygenase; DNA-binding; Iron; Isopeptide bond; Leucine-rich repeat; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger

A

45337.4

386

0.12

31.19

5.5

-12.12

-5.55

UCHL3

Homo sapiens (Human)

Ubiquitin carboxyl-terminal hydrolase isozyme L3; UCH-L3

Peptidase C12 family

Peptidase

Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins.

Epilepsy, familial focal, with variable foci 4 (FFEVF4) [MIM:617935]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. FFEVF4 is characterized by onset of focal seizures in the first years of life. {ECO:0000269|PubMed:24157691, ECO:0000269|PubMed:28235671}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 62 (DEE62) [MIM:617938]: 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. DEE62 is characterized by onset of seizures in the first year of life. {ECO:0000269|PubMed:29466837}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9H078; G5E9A7; Q15797; Q7Z699

EC 3.4.19.12

3D-structure; Cytoplasm; Hydrolase; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation pathway

A,B

34540.8

304

0.07

39.91

5.01

-17.24

-5.55

PON1

Homo sapiens (Human)

NA

PON

Paraoxonase family

Hydrolase

Acyl-L-homoserine-lactone lactonohydrolase activity.Aryldialkylphosphatase activity.Arylesterase activity.Calcium ion binding.Phospholipid binding.Protein homodimerization activity.

Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.

DB01327; DB09130; DB01395; DB14598; DB14600; DB14596; DB00218; DB01085; DB01593; DB14487; DB14533; DB14548

NA

3.1.1.2; 3.1.1.81; 3.1.8.1

3D-structure; Calcium; Direct protein sequencing; Disulfide bond; Glycoprotein; HDL; Hydrolase; Metal-binding; Proteomics identification; Reference proteome; Secreted; Signal

A

37232.8

332

0.11

35.09

5.06

-17.08

-5.53

ponA

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

NA

SP_0369

Glycosyltransferase 51 family; Transpeptidase family

Biosynthetic protein

Penicillin binding.Peptidoglycan glycosyltransferase activity.Serine-type D-Ala-D-Ala carboxypeptidase activity.

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

DB01150; DB05659

NA

2.4.99.28; 3.4.16.4

3D-structure; Antibiotic resistance; Carboxypeptidase; Cell shape; Cell wall biogenesis/degradation; Glycosyltransferase; Hydrolase; Multifunctional enzyme; Peptidoglycan synthesis; Protease; Reference proteome; Secreted; Transferase

A,C

44805.1

400

0.12

31.82

4.88

-14.68

-5.54

pelA

Niveispirillum irakense (Azospirillum irakense)

NA

NA

NA

Lyase

Lyase activity.

A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. {ECO:0000269|PubMed:15938644}.; DISEASE: A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. {ECO:0000269|PubMed:12112524, ECO:0000269|PubMed:16161041}.; DISEASE: A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. {ECO:0000269|PubMed:12112524}.; DISEASE: Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. {ECO:0000269|PubMed:18724359, ECO:0000269|PubMed:18923523, ECO:0000269|PubMed:18923525, ECO:0000269|PubMed:21242967, ECO:0000269|PubMed:22932897}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth. {ECO:0000269|PubMed:15908427}.; DISEASE: A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion. {ECO:0000269|PubMed:22327622}.; DISEASE: A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation. {ECO:0000269|PubMed:17625570}.

NA

NA

NA

3D-structure; Lyase; Signal

A

41907.5

384

0.08

43.72

6.11

-3.46

-5.54

HDAC8

Homo sapiens (Human)

Histone deacetylase-8; HDACL1; HD8; CDA07

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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22885700, ECO:0000269|PubMed:22889856}. The disease is caused by variants affecting the gene represented in this entry.

DB07350; DB02565; DB07586; DB12565; DB05015; DB08168; DB01262; DB11841; DB14490; DB14491; DB14488; DB14501; DB14489; DB12645; DB01592; DB02917; DB06603; DB06819; DB03766; DB12847; DB06176; DB04297; DB00313; DB02546; DB01593; DB14487; DB14533; DB14548

NA

EC 3.5.1.98

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Cytoplasm; Disease variant; Hydrolase; Intellectual disability; Metal-binding; Nucleus; Obesity; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; Transcription; Transcription regulation

A,B

39018.4

351

0.11

38.57

6.06

-5.26

-5.53

ALDH1A3

Homo sapiens (Human)

NA

ALDH6

Aldehyde dehydrogenase family

Oxidoreductase

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

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

DB00157; DB00162

NA

1.2.1.36

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

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

50635.7

461

0.09

33.75

7.07

0.15

-5.52

PHF8

Homo sapiens (Human)

ZNF422; PHD finger protein 8; KIAA1111

JHDM1 histone demethylase family, JHDM1D subfamily

Paired donor oxygen oxidoreductase

Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development.

Intellectual developmental disorder, X-linked, syndromic, Siderius type (MRXSSD) [MIM:300263]: A syndrome characterized by mild to borderline intellectual disability with or without cleft lip/cleft palate. {ECO:0000269|PubMed:16199551, ECO:0000269|PubMed:17661819, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q96QS3; Q06330; Q9Y462; P51610-1; Q15156; P10276

EC 1.14.11.27

3D-structure; Activator; Alternative splicing; Cell cycle; Chromatin regulator; Dioxygenase; Disease variant; Intellectual disability; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A,B

51141.1

446

0.11

44.47

6.21

-4.56

-5.52

UCHL1

Homo sapiens (Human)

Ubiquitin thiolesterase L1; Ubiquitin carboxyl-terminal hydrolase isozyme L1; Ubiquitin carboxy-terminal hydrolase L1; UCH-L1; PGP9.5; PGP 9.5; Neuron cytoplasmic protein 9.5

Peptidase C12 family

Peptidase

Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

Parkinson disease 5 (PARK5) [MIM:613643]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. {ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:9774100}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 79A, autosomal dominant, with ataxia (SPG79A) [MIM:620221]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79A is a slowly progressive form characterized by late-onset spastic ataxia, neuropathy, and often optic atrophy. {ECO:0000269|PubMed:35986737}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 79B, autosomal recessive (SPG79B) [MIM:615491]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79B is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction. {ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:28007905}. The disease is caused by variants affecting the gene represented in this entry.

DB12695

P63010-2; P05067; P05067-2; Q8N6T3-3; P18847; Q9H1Y0; O15392; Q8WUW1; P83916; P11802; Q00535; Q9UNS2; Q92905; P00533; O60739; Q8TC29; Q9UI08-2; Q8WVV9-3; Q14164; Q6DN90-2; Q96JM7-2; P13473-2; Q9BYZ2; O95777; A4FUJ8; Q15843; O15381-5; Q9BR81; Q13113; P62826; Q8TAI7; Q9ULX5; Q15554-4; Q9NYB0; P04637; Q9Y4K3; P19474; Q9BSL1; Q7KZS0; P61086; Q9UK80; Q86WB0-2

EC 3.4.19.12

3D-structure; Cytoplasm; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Glycoprotein; Hereditary spastic paraplegia; Hydrolase; Lipoprotein; Membrane; Neurodegeneration; Oxidation; Parkinson disease; Parkinsonism; Phosphoprotein; Prenylation; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation pathway

A,B

33389.8

298

0.07

38.69

5.51

-7.88

-5.52

HDAC7

Homo sapiens (Human)

Histone deacetylase 7A; HDAC7A; HD7a; HD7

Histone deacetylase family, HD type 2 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. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene. Positively regulates the transcriptional repressor activity of FOXP3. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

Mucopolysaccharidosis 1H (MPS1H) [MIM:607014]: A severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe intellectual disability. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age. {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:1301941, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:24036510, ECO:0000269|PubMed:31194252, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:7951228, ECO:0000269|PubMed:8019563, ECO:0000269|PubMed:8328452, ECO:0000269|PubMed:8401515, ECO:0000269|Ref.20}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 1H/S (MPS1H/S) [MIM:607015]: A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. {ECO:0000269|PubMed:10466419, ECO:0000269|PubMed:10735634, ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8401515}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 1S (MPS1S) [MIM:607016]: A mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding. {ECO:0000269|PubMed:12559846, ECO:0000269|PubMed:15300847, ECO:0000269|PubMed:19396826, ECO:0000269|PubMed:21394825, ECO:0000269|PubMed:25256405, ECO:0000269|PubMed:7550232, ECO:0000269|PubMed:7550242, ECO:0000269|PubMed:8213840}. The disease is caused by variants affecting the gene represented in this entry.

DB12565; DB05015; DB01262; DB11841; DB12645; DB06603; DB06819; DB03766; DB12847; DB06176; DB04297; DB00313; DB02546

P00533; Q9BZS1-1; Q9BZS1-2; Q9BZL6; P31947; P63104; P08393; Q8CFN5; Q13137; Q04864; Q0D2K3; Q8WXI4-2; Q9BQD7; Q03989; Q9NSI6-4; Q3SXR2; Q13137; P60953; Q7L2Z9; Q96D03; Q9NQ30; Q9UBI6; A6NEM1; A5PKX9; Q9BXK1; Q6ZNG9; O43679; Q6FHY5; Q9BRT3; O94964-4; O95411; O00746; Q9BQI9; B7ZLY0; Q96I34; P63000; P15153; P60763; Q04864-2; Q0D2K3; P62070; O15427; O95164

EC 3.5.1.98

3D-structure; Alternative splicing; Chromatin regulator; Cytoplasm; Hydrolase; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Zinc

A

41454.5

383

0.08

38.49

6.26

-5.18

-5.52

cocE

Rhodococcus sp. (strain MB1 Bresler)

NA

NA

CocE/NonD hydrolase family

Hydrolase

Carboxylic ester hydrolase activity.Dipeptidyl-peptidase activity.

Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5) [MIM:614458]: An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits. {ECO:0000269|PubMed:22152682}. The disease is caused by variants affecting the gene represented in this entry.

DB03793; DB01795

NA

3.1.1.84

3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase; Serine esterase

A

62127.9

574

0.09

26.62

4.56

-33.24

-5.51

MAT2A

Homo sapiens (Human)

Methionine adenosyltransferase II; Methionine adenosyltransferase 2; MAT-II; MAT 2; AdoMet synthase 2

AdoMet synthase family

AdoMet synthase family

Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB00118; DB00134

Q96IK1-2; Q96NX5; Q6ZP82-1; Q8IUI8; Q6P1L5; P15976-2; P80217-2; Q8WZ19; Q9UIH9; Q00266; P31153; Q9NZL9; P02795; Q9BRX2; O43663; O43741; P57052; Q8N488; P08195-4; Q13573; Q86W54-2; O95789-4

EC 2.5.1.6

3D-structure; Acetylation; Alternative splicing; ATP-binding; Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; One-carbon metabolism; Phosphoprotein; Potassium; Proteomics identification; Reference proteome; Transferase; Ubl conjugation

A

42071.4

381

0.08

38.24

6.21

-4.13

-5.49

FLT3

Homo sapiens (Human)

Stem cell tyrosine kinase 1; STK1; STK-1; Receptor-type tyrosine-protein kinase FLT3; Fetal liver kinase-2; FLT-3; FLK2; FLK-2; FL cytokine receptor; CD135

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

Kinase

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.

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. {ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:11290608, ECO:0000269|PubMed:11442493, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:18305215, ECO:0000269|PubMed:8946930, ECO:0000269|PubMed:9737679}. The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent 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 activation loop of the kinase domain can result in a constitutively activated kinase.

DB12742; DB12267; DB12500; DB12010; DB12141; DB06469; DB06080; DB06595; DB11763; DB09079; DB11697; DB12978; DB08901; DB15822; DB12874; DB00398; DB01268; DB05465; DB11800; DB05014

P00519; P42684; P46108; P46109; P06241; Q13322; Q9Y6K9; P06239; P27986; P20936; P43405; Q8R4L0

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Host-virus interaction; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

34209.2

298

0.14

39.68

5.57

-4.02

-5.5

bla

Klebsiella pneumoniae

NA

kpc;kpc1

Class-A beta-lactamase family

Hydrolase / hydrolase inhibitor

Beta-lactamase activity.

Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22885700, ECO:0000269|PubMed:22889856}. The disease is caused by variants affecting the gene represented in this entry.

DB09060; DB12107

NA

3.5.2.6

3D-structure; Antibiotic resistance; Hydrolase; Plasmid; Signal

A

27965.2

264

0.08

26.27

6.14

-1.42

-5.49

KDM7A

Homo sapiens (Human)

Lysine-specific demethylase 7; KIAA1718; KDM7; JmjC domain-containing histone demethylation protein 1D; JHDM1D

JHDM1 histone demethylase family, JHDM1D subfamily

NA

Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate.

MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. {ECO:0000269|PubMed:20816948}.; DISEASE: Tubulointerstitial kidney disease, autosomal dominant, 2 (ADTKD2) [MIM:174000]: A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance. {ECO:0000269|PubMed:23396133}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.14.11.-

3D-structure; Alternative splicing; Chromatin regulator; Dioxygenase; Iron; Metal-binding; Neurogenesis; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A

42365.5

366

0.12

41.95

6.3

-3.09

-5.5

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

-5.49

PPOX

Homo sapiens (Human)

PPO

Protoporphyrinogen/coproporphyrinogen oxidase family, Protoporphyrinogen oxidase subfamily

NA

Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.

Variegate porphyria (VP) [MIM:176200]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Variegate porphyria is an acute hepatic form characterized by partial reduction of protoporphyrinogen oxidase activity, increased photosensitivity, skin blistering and scarring of sun-exposed areas, skin hyperpigmentation, abdominal pain, and neuropsychiatric symptoms. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease. Inheritance is autosomal dominant with incomplete penetrance. {ECO:0000269|PubMed:10486317, ECO:0000269|PubMed:11074242, ECO:0000269|PubMed:11102990, ECO:0000269|PubMed:11348478, ECO:0000269|PubMed:11350188, ECO:0000269|PubMed:11474578, ECO:0000269|PubMed:12380696, ECO:0000269|PubMed:12655566, ECO:0000269|PubMed:12859407, ECO:0000269|PubMed:12922165, ECO:0000269|PubMed:14669009, ECO:0000269|PubMed:16433813, ECO:0000269|PubMed:16621625, ECO:0000269|PubMed:16922948, ECO:0000269|PubMed:16947091, ECO:0000269|PubMed:18350656, ECO:0000269|PubMed:18570668, ECO:0000269|PubMed:19320019, ECO:0000269|PubMed:21048046, ECO:0000269|PubMed:23430901, ECO:0000269|PubMed:23467411, ECO:0000269|PubMed:24073655, ECO:0000269|PubMed:8817334, ECO:0000269|PubMed:8852667, ECO:0000269|PubMed:9763307}. The disease is caused by variants affecting the gene represented in this entry. Mutations leading to severe PPOX deficiency cause the rare homozygous variant form of VP. Missense mutations that preserve 10%-25% of wild-type activity may not cause clinically overt VP in heterozygotes (PubMed:9811936). Mutations with intermediate effect on catalytic activity may cause VP, but with a low clinical penetrance (PubMed:10486317). {ECO:0000269|PubMed:10486317, ECO:0000269|PubMed:9811936}.; DISEASE: Variegate porphyria, childhood-onset (VPCO) [MIM:620483]: An autosomal recessive form of variegate porphyria, a disorder of heme biosynthesis that results from diminished activity of protoporphyrinogen oxidase. VPCO is characterized by severe protoporphyrinogen oxidase deficiency, onset of photosensitization by porphyrins in early childhood, skin scarring and hyperpigmentation, and skeletal abnormalities of the hand. Additional variable features are short stature, impaired intellectual development, and seizures. VPCO patients rarely experience acute neuropsychiatric or abdominal attacks. {ECO:0000269|PubMed:10870850, ECO:0000269|PubMed:11286631, ECO:0000269|PubMed:33159949, ECO:0000269|PubMed:8673113, ECO:0000269|PubMed:9541112, ECO:0000269|PubMed:9811936}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.3.3.4

3D-structure; Disease variant; FAD; Flavoprotein; Heme biosynthesis; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Porphyrin biosynthesis; Proteomics identification; Reference proteome

A

49470.2

465

0.05

48.23

7.8

1.98

-5.5

USP1

Homo sapiens (Human)

hUBP; Ubiquitin-specific-processing protease 1; Ubiquitin thioesterase 1; Ubiquitin carboxyl-terminal hydrolase 1

Peptidase C19 family

Peptidase

Involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2.

Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}. The gene represented in this entry is involved in disease pathogenesis. Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}.; DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (SSFSC1) [MIM:617877]: An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract. {ECO:0000269|PubMed:29198724}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q8TAF3; Q8TAF3-1

EC 3.4.19.12

3D-structure; Autocatalytic cleavage; DNA damage; DNA repair; Hydrolase; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation; Ubl conjugation pathway

D

32426

285

0.1

50.73

5.85

-4.67

-5.49

KLKB1

Homo sapiens (Human)

Plasma prekallikrein; Plasma kallikrein light chain; Plasma kallikrein heavy chain; PKK; Kininogenin; KLK3; Fletcher factor

Peptidase S1 family, Plasma kallikrein subfamily

Peptidase

It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin. The enzyme cleaves Lys-Arg and Arg-Ser bonds.

Prekallikrein deficiency (PKKD) [MIM:612423]: An autosomal recessive condition characterized by a clotting defect due to prolongation of activated partial thromboplastin time. Affected individuals are clinically asymptomatic. {ECO:0000269|PubMed:14652634, ECO:0000269|PubMed:17598838, ECO:0000269|PubMed:34847617}. The disease is caused by variants affecting the gene represented in this entry.

DB15982; DB09228; DB05311; DB12831; DB06404; DB14597; DB01593; DB14487; DB14533; DB14548

Q9UI10; O00746; C9J082; O14744; Q8TAS3; O00233; Q8IYM2; Q9UMY4; O43493-5; Q8NFB2; Q8N0U8

EC 3.4.21.34

3D-structure; Blood coagulation; Direct protein sequencing; Disease variant; Disulfide bond; Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase; Inflammatory response; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen

A

26696.2

237

0.1

34.33

8.07

2.21

-5.5