Malaria ht1

Plasmodium falciparum (malaria parasite P. falciparum)

ht1; Putative sugar transporter; Hexose transporter

Major facilitator superfamily, Sugar transporter (TC 2.A.1.1) family

NA

High-affinity glucose transporter.

Nivelon-Nivelon-Mabille syndrome (NNMS) [MIM:600092]: An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present. {ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:30912300}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Cell membrane; Disulfide bond; Membrane; Sugar transport; Transmembrane; Transmembrane helix; Transport

A

53412.5

476

0.14

28.88

8.51

4.43

-10.41

MAPK11

Homo sapiens (Human)

Stress-activated protein kinase-2; SAPK2b; SAPK2; PRKM11; P38b; P38-2; P38 Mitogen-activated protein kinase beta; Mitogen-activated protein kinase p38 beta; Mitogen-activated protein kinase 11; MAPK 1

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily

Kinase

MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Amyotrophic lateral sclerosis 19 (ALS19) [MIM:615515]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:24119685}. The disease is caused by variants affecting the gene represented in this entry.

DB05157; DB01017; DB08896

Q86V38; P02489; P50570-2; Q14204; P22607; O14908-2; Q92993; Q92876; Q8TAP4-4; Q16644; Q13153; P17252; Q15047-2; Q16637; Q13148; P04637; P61981; O43257

EC 2.7.11.24

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Stress response; Transcription; Transcription regulation; Transferase

A

38199.3

333

0.09

46.97

5.64

-8.6

-10.39

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

-10.38

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

-10.38

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

-10.38

MDM4

Homo sapiens (Human)

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

MDM2/MDM4 family

MDM2/MDM4 family

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

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

NA

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

NA

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

A,B

19722

173

0.08

50.78

8.48

2.27

-10.38

ROR1

Homo sapiens (Human)

receptor tyrosine kinase-like orphan receptor 1; receptor tyrosine kinase like orphan receptor 1; neurotrophic tyrosine kinase, receptor-related 1; dJ537F10.1; Tyrosine-protein kinase transmembrane re

Protein kinase superfamily, Tyr protein kinase family, ROR subfamily

Kinase

Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling. In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells. Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo.

Deafness, autosomal recessive, 108 (DFNB108) [MIM:617654]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:27162350}. The disease is caused by variants affecting the gene represented in this entry.

NA

P00533; P12931; P05480

NA

3D-structure; Alternative splicing; ATP-binding; Cell projection; Deafness; Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Kringle; Membrane; Non-syndromic deafness; Nucleotide-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transferase; Transmembrane; Transmembrane helix; Wnt signaling pathway

A

31123.7

267

0.12

60.72

6.13

-4.3

-10.38

frdA

Escherichia coli (strain K12)

NA

JW4115;b4154

FAD-dependent oxidoreductase 2 family, FRD/SDH subfamily

Oxidoreductase

Electron carrier activity.FAD binding.Fumarate reductase (menaquinone).Succinate dehydrogenase activity.

Glycogen storage disease 11 (GSD11) [MIM:612933]: A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. {ECO:0000269|PubMed:2334430}. The disease is caused by variants affecting the gene represented in this entry.

DB07490; DB07918; DB00730

P0AC47; P0ACB4; P76111

1.3.5.1

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; Electron transport; FAD; Flavoprotein; Membrane; Nucleotide-binding; Oxidoreductase; Reference proteome; Transport

A,M

90370.7

820

0.08

28.88

5.86

-16.21

-10.36

NR1H4

Homo sapiens (Human)

NA

HRR1;BAR;RIP14;FXR

Nuclear hormone receptor family, NR1 subfamily

Transcription

Bile acid binding.Bile acid receptor activity.Chenodeoxycholic acid binding.Ligand-dependent nuclear receptor binding.Retinoid X receptor binding.RNA polymerase II distal enhancer sequence-specific DNA binding.RNA polymerase II regulatory region sequence-specific DNA binding.RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding.Sequence-specific DNA binding.Steroid hormone receptor activity.Thyroid hormone receptor activity.Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding.Transcriptional activator activity, RNA polymerase II transcription factor binding.Transcription coactivator activity.Transcription corepressor activity.Transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding.Transcription factor activity, sequence-specific DNA binding.Transcription regulatory region sequence-specific DNA binding.Zinc ion binding.

May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305|PubMed:17681172}.; DISEASE: May be involved in cholesterol cholelithiasis. {ECO:0000305|PubMed:17931734}.; DISEASE: Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. {ECO:0000269|PubMed:26888176}. The disease is caused by variants affecting the gene represented in this entry.

DB08220; DB00132; DB04557; DB06777; DB02659; DB03619; DB02509; DB02545; DB11605; DB16255; DB05990; DB04348; DB16343; DB01586

Q15788; O75151; Q8WTS6; P28702; P28702-3; P48443; Q15788; P78527; P03372

NA

3D-structure; Acetylation; Activator; Alternative promoter usage; Alternative splicing; Disease variant; DNA-binding; Immunity; Inflammatory response; Innate immunity; Intrahepatic cholestasis; Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

28271.2

241

0.08

47.06

5.39

-11.24

-10.37

SMYD3

Homo sapiens (Human)

SET and MYND domain-containing protein 3; Zinc finger MYND domain-containing protein 1

Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family

NA

Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation . Also methylates 'Lys-5' of histone H4. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.

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:17332249}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 6 (NS6) [MIM:613224]: 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. {ECO:0000269|PubMed:19966803}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: RAS-associated autoimmune leukoproliferative disorder (RALD) [MIM:614470]: A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies. {ECO:0000269|PubMed:17517660}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanocytic nevus syndrome, congenital (CMNS) [MIM:137550]: A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip. {ECO:0000269|PubMed:18633438, ECO:0000269|PubMed:23392294}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanosis, neurocutaneous (NCMS) [MIM:249400]: A rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma. {ECO:0000269|PubMed:23392294}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]: Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. {ECO:0000269|PubMed:22499344}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12727991}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

NA

Q9H0L4; Q9H0I2; Q13064; Q7Z3B4; Q16512; Q92529; Q15915; Q9Y2U5

EC 2.1.1.354

3D-structure; Acetylation; Alternative splicing; Chromatin regulator; Cytoplasm; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger

A

48694.1

425

0.08

44.91

6.86

-0.4

-10.35

FABP2

Homo sapiens (Human)

NA

FABPI

Calycin superfamily, Fatty-acid binding protein (FABP) family

Transport protein

Fatty acid binding.Transporter activity.

Usher syndrome 3B (USH3B) [MIM:614504]: A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. {ECO:0000269|PubMed:22279524}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, 2W (CMT2W) [MIM:616625]: An autosomal dominant, 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. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement. {ECO:0000269|PubMed:22930593, ECO:0000269|PubMed:26072516, ECO:0000269|PubMed:29235198}. The disease is caused by variants affecting the gene represented in this entry.

DB04557; DB09213; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB01050; DB08231; DB03796; DB01138

O95994; Q9NYB0

NA

3D-structure; Acetylation; Cytoplasm; Lipid-binding; Proteomics identification; Reference proteome; Transport

A,B,C,D

15075.9

131

0.11

32.01

6.88

-0.09

-10.34

DDR1

Homo sapiens (Human)

Tyrosine-protein kinase CAK; Tyrosine kinase DDR; TRKE; TRK E; RTK6; Protein-tyrosine kinase RTK-6; Protein-tyrosine kinase 3A; PTK3A; NTRK4; NEP; Mammary carcinoma kinase 10; MCK-10; HGK2; Epithelial

Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily

Kinase

Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11. Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation.

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.

DB12010; DB00619; DB15822

Q16832; O43639; Q06124; Q9UHD9

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Calcium; Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein; Kinase; Lactation; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Pregnancy; Proteomics identification; Receptor; Reference proteome; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase

A,B

34061.1

297

0.1

42.8

6.32

-2.01

-10.33

NTRK1

Homo sapiens (Human)

NA

TRKA;TRK;MTC

Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily

Transferase / transferase inhibitor

ATP binding.GPI-linked ephrin receptor activity.Kinase binding.Nerve growth factor binding.Nerve growth factor receptor activity.Neurotrophin binding.Neurotrophin p75 receptor binding.Protein homodimerization activity.Protein tyrosine kinase activity.Transmembrane receptor protein tyrosine kinase activity.

Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and intellectual disability. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. {ECO:0000269|PubMed:10090906, ECO:0000269|PubMed:10233776, ECO:0000269|PubMed:10330344, ECO:0000269|PubMed:10567924, ECO:0000269|PubMed:10861667, ECO:0000269|PubMed:10982191, ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:11310631, ECO:0000269|PubMed:18077166, ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573, ECO:0000269|PubMed:28328124, ECO:0000269|PubMed:8696348}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:1532241, PubMed:2869410, PubMed:7565764). Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 (PubMed:7565764). A rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein (PubMed:1532241). {ECO:0000269|PubMed:1532241, ECO:0000269|PubMed:2869410, ECO:0000269|PubMed:7565764}.

DB00321; DB13926; DB11986; DB12010; DB00619; DB14723; DB15822; DB08896; DB16826

P05067-4; P22681; P08238; P01138; PRO_0000019600 [P01138]; P04629; Q16288; P27986; P19174; P18031; Q99523; Q13501; O75385; Q8K4V6

2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Developmental protein; Differentiation; Disease variant; Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

31968.8

280

0.1

47.51

8.96

7.04

-10.32

PDE3A

Homo sapiens (Human)

cGMP-inhibited 3',5'-cyclic phosphodiesterase A; Phosphodiesterase 3A; Cyclic GMP-inhibited phosphodiesterase A; Cyclic GMP inhibited phosphodiesterase A; CGI-PDE A

Cyclic nucleotide phosphodiesterase family, PDE3 subfamily

Phosphoric diester hydrolase

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

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.

DB01223; DB01427; DB00261; DB00201; DB01166; DB04880; DB05266; DB00922; DB00235; DB01303; DB00277; DB08811; DB09283

Q9Y6D6; Q9Y6D5

EC 3.1.4.17

3D-structure; cAMP; cGMP; Cytoplasm; Direct protein sequencing; Disease variant; Hydrolase; Isopeptide bond; Manganese; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation

A,B

108171

939

0.11

39.75

6.53

-4.15

-10.33

CYP1A2

Homo sapiens (Human)

NA

NA

Cytochrome P450 family

Oxidoreductase

Aromatase activity.Caffeine oxidase activity.Demethylase activity.Electron carrier activity.Enzyme binding.Heme binding.Iron ion binding.Monooxygenase activity.Oxidoreductase activity.Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen.Oxygen binding.

Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. The disease is caused by variants affecting the gene represented in this entry.

DB08496; DB01667; DB14132; DB04356; DB02489; DB11932; DB12001; DB05812; DB13573; DB01418; DB00316; DB15568; DB06594; DB00518; DB05396; DB00969; DB07453; DB01424; DB01223; DB01118; DB00321; DB00261; DB01217; DB01435; DB06605; DB05676; DB06413; DB06216; DB01072; DB15011; DB06442; DB06626; DB00993; DB00972; DB13203; DB05015; DB16703; DB06769; DB01086; DB06770; DB06771; DB06732; DB00195; DB04889; DB11967; DB13975; DB00188; DB12151; DB01558; DB14018; DB13812; DB00201; DB09061; DB14737; DB11791; DB06774; DB00564; DB06016; DB01136; DB12814; DB00477; DB00356; DB01166; DB00501; DB01012; DB00568; DB00827; DB00537; DB00215; DB12499; DB14025; DB00349; DB01242; DB00575; DB00758; DB00363; DB00286; DB11672; DB14635; DB00924; DB08912; DB00851; DB06292; DB01254; DB01609; DB01151; DB16650; DB12161; DB01191; DB00633; DB11994; DB00586; DB11511; DB12945; DB00280; DB01184; DB09167; DB05928; DB01142; DB09273; DB00470; DB00476; DB00625; DB15444; DB06210; DB13874; DB11718; DB00467; DB11404; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00655; DB04574; DB13592; DB00330; DB00898; DB00977; DB00773; DB01628; DB00927; DB04854; DB01482; DB00574; DB12265; DB15669; DB01195; DB08972; DB04841; DB00544; DB00472; DB00499; DB00176; DB01320; DB00998; DB14029; DB06160; DB01044; DB01241; DB01155; DB01645; DB01381; DB00986; DB00365; DB00400; DB05708; DB00629; DB00502; DB01094; DB14999; DB04076; DB11737; DB00619; DB00458; DB11564; DB01306; DB09456; DB09564; DB01307; DB00047; DB01309; DB00030; DB00046; DB11567; DB00071; DB11568; DB05258; DB00034; DB00105; DB15131; DB00011; DB00018; DB00069; DB00060; DB00068; DB00033; DB00951; DB11757; DB09570; DB01026; DB01097; DB16217; DB09078; DB01002; DB05667; DB00281; DB12406; DB09198; DB04948; DB00978; DB06448; DB16220; DB01601; DB00455; DB04871; DB06077; DB01283; DB00772; DB00934; DB06234; DB14009; DB00784; DB01065; DB00170; DB00454; DB00532; DB00333; DB00763; DB00553; DB01028; DB09241; DB01233; DB00379; DB06148; DB01388; DB06595; DB00370; DB16236; DB00745; DB11763; DB00218; DB06510; DB14011; DB00461; DB00607; DB00779; DB00788; DB06600; DB00238; DB06803; DB00184; DB01115; DB11793; DB00435; DB05115; DB00717; DB01059; DB00540; DB05990; DB01165; DB00334; DB16267; DB00338; DB00904; DB11632; DB11443; DB01173; DB11837; DB09330; DB01303; DB11697; DB00377; DB00715; DB06589; DB11774; DB00487; DB00008; DB00022; DB09122; DB13634; DB00806; DB11198; DB08883; DB00850; DB03783; DB01174; DB00388; DB00252; DB11450; DB01100; DB13823; DB04951; DB17472; DB11642; DB08910; DB15822; DB01058; DB01087; DB00794; DB00420; DB09288; DB01182; DB06479; DB00818; DB00571; DB13449; DB11892; DB04216; DB00908; DB00468; DB01129; DB00980; DB09290; DB00863; DB01367; DB00409; DB02709; DB13174; DB01045; DB11753; DB00740; DB14924; DB00503; DB00533; DB01656; DB15119; DB00268; DB00296; DB00412; DB00817; DB12332; DB13772; DB06654; DB11491; DB00418; DB01037; DB11689; DB06290; DB13261; DB15093; DB00052; DB00398; DB01208; DB09118; DB00428; DB06820; DB00382; DB00675; DB06083; DB09071; DB05488; DB09256; DB01079; DB01405; DB00857; DB08880; DB11712; DB01412; DB00277; DB00730; DB01623; DB00208; DB06137; DB00697; DB01056; DB06264; DB00752; DB00384; DB12245; DB00831; DB15442; DB00440; DB00685; DB08867; DB14989; DB13609; DB06235; DB00313; DB08881; DB00661; DB09185; DB12026; DB00682; DB02134; DB00549; DB00744; DB00315; DB00425; DB09225; DB09120

O95870

1.14.14.1; 4.2.1.152

3D-structure; Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism

A

54475

480

0.1

40.43

9.16

9.89

-10.31

soxA

Bacillus sp. (strain B-0618)

NA

sox

MSOX/MTOX family, MSOX subfamily

Oxidoreductase

Sarcosine oxidase activity.

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

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

NA

1.5.3.1

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

A,B

42606.4

385

0.1

26.97

5.27

-17.18

-10.31

SMYD2

Homo sapiens (Human)

Nlysine methyltransferase SMYD2; N-lysine methyltransferase SMYD2; Lysine Nmethyltransferase 3C; Lysine N-methyltransferase 3C; KMT3C; Histone methyltransferase SMYD2; HSKMB; HSKM-B

Class V-like SAM-binding methyltransferase superfamily

Methyltransferase

Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'. Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1.

Pulmonary hypertension, primary, 4 (PPH4) [MIM:615344]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269|PubMed:23883380}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in this gene may cause developmental delay with sleep apnea (DDSA). A disorder characterized by developmental neurologic, skeletal and respiratory anomalies including microcephaly, arthrogryposis, scoliosis, cleft palate, facial dysmorphology, bilateral talipes, feeding difficulties and central and/or obstructive sleep apnea. Malformations are detected as early as 21 weeks post gestation. Severely affected patients require ongoing treatment with nocturnal O2 or pressure-controlled ventilation. The disease is associated with recurrent de novo gain of function variants. {ECO:0000269|PubMed:36195757}.

NA

P20290-2; Q96K17; Q9UPZ9; Q9Y5W9; P04637

EC 2.1.1.-

3D-structure; Alternative splicing; Chromatin regulator; Cytoplasm; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Zinc; Zinc-finger

A

48789.6

425

0.1

51.93

6.35

-4.02

-10.31

DPP8

Homo sapiens (Human)

Prolyl dipeptidase DPP8; MSTP141; MSTP135; MSTP097; Dipeptidyl peptidase VIII; Dipeptidyl peptidase IV-related protein 1; DPRP1; DPRP-1; DPP VIII; DP8

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.

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.14.5

3D-structure; Alternative splicing; Aminopeptidase; Apoptosis; Cytoplasm; Hydrolase; Protease; Proteomics identification; Reference proteome; Serine protease

A,D

97764.9

849

0.12

47.71

5.69

-21.66

-10.3

MGLL

Homo sapiens (Human)

Monoacylglycerol lipase; MGL; Lysophospholipaselike; Lysophospholipase-like; Lysophospholipase homolog; HUK5; HU-K5

AB hydrolase superfamily, Monoacylglycerol lipase family

Carboxylic ester hydrolase

Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth. Converts monoacylglycerides to free fatty acids and glycerol.

Systemic lupus erythematosus 9 (SLEB9) [MIM:610927]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17360460}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency, common variable, 7 (CVID7) [MIM:614699]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:22035880}. The disease is caused by variants affecting the gene represented in this entry.

NA

P07550; P37235

EC 3.1.1.23

3D-structure; Alternative splicing; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Lipid biosynthesis; Lipid degradation; Lipid metabolism; Membrane; Nitration; Phosphoprotein; Proteomics identification; Reference proteome; Serine esterase

A

31808.4

289

0.08

29.7

6.73

-0.91

-10.29

MAP3K20

Homo sapiens (Human)

ZAK; Sterile alpha motif- and leucine zipper-containing kinase AZK; Mixed lineage kinase-related kinase; Mitogen-activated protein kinase kinase kinase MLT; Mitogen-activated protein kinase kinase kin

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily

NA

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Involved in limb development.

Split-foot malformation with mesoaxial polydactyly (SFMMP) [MIM:616890]: An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss. {ECO:0000269|PubMed:26755636, ECO:0000269|PubMed:32266845}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6) [MIM:617760]: A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood. {ECO:0000269|PubMed:27816943, ECO:0000269|PubMed:30237576}. The disease is caused by variants affecting the gene represented in this entry.

DB01254; DB12010

O75582; P31947; P63104; Q8N184; Q16512; Q6P2D0; Q6ZN57; P13682; Q8N184; Q6AZW8; Q9NQZ8

EC 2.7.11.25

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

A,B

64591.5

566

0.1

52.08

5.69

-12.83

-10.29