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

-7.75

CCNE1

Homo sapiens (Human)

G1/S-specific cyclin E; Cyclin E; CCNE

Cyclin family, Cyclin E subfamily

NA

Essential for the control of the cell cycle at the G1/S (start) transition.

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

NA

P38398; P24941; P38936; P46527; Q08050; A6NCL1; Q96PU4; Q5VK71

NA

3D-structure; Alternative splicing; Cell cycle; Cell division; Cyclin; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A

33714.8

297

0.1

34.11

8.8

4.38

-7.75

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

-7.75

CASP7

Homo sapiens (Human)

MCH3; ICE-like apoptotic protease 3; ICE-LAP3; CMH-1; CASP-7; Apoptotic protease Mch-3

Peptidase C14A family

Peptidase

Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution.

Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:17339269}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB05408; DB03384; DB06255

Q13490; P83105; P42858; Q8N4N3-2; P43364; Q16236; Q9GZT8; Q13177; P27986-2; P21673; Q86WV1-2; P17405; P98170

EC 3.4.22.60

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; Apoptosis; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; RNA-binding; Secreted; Thiol protease; Ubl conjugation; Zymogen

A,B

47441.5

417

0.11

20.98

8.38

6.12

-7.75

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

-7.74

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

-7.74

treA

Escherichia coli (strain K12)

NA

JW1186;osmA;b1197

Glycosyl hydrolase 37 family

NA

Provides the cells with the ability to utilize trehalose at high osmolarity by splitting it into glucose molecules that can subsequently be taken up by the phosphotransferase-mediated uptake system.

SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells. {ECO:0000269|PubMed:2498394, ECO:0000269|PubMed:3093483}.; DISEASE: Thrombocytopenia 6 (THC6) [MIM:616937]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis. {ECO:0000269|PubMed:26936507}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

3.2.1.28

3D-structure; Direct protein sequencing; Glycosidase; Hydrolase; Periplasm; Reference proteome; Signal

A

57508.9

507

0.11

48.32

5.48

-10.13

-7.73

TNKS2

Homo sapiens (Human)

Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribos

ARTD/PARP family

Glycosyltransferases

Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. {ECO:0000269|PubMed:30290153}. The disease is caused by variants affecting the gene represented in this entry.

NA

O15084; Q7Z6K5-1; O15169; Q9NWV8; P11274; Q13698; Q9NRI5; Q6V0I7; Q9NWT6; P14652; Q9UIQ6; Q14980; Q9BZL4; Q92698; P78314; O43815; P54274; Q9C0C2; Q9UHP3; Q06649

EC 2.4.2.30

3D-structure; ADP-ribosylation; ANK repeat; Chromosome; Cytoplasm; Glycosyltransferase; Golgi apparatus; Hydroxylation; Membrane; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Proteomics identification; Reference proteome; Repeat; Telomere; Transferase; Ubl conjugation; Wnt signaling pathway; Zinc

A

23695.5

208

0.11

47.61

8.28

2.88

-7.74

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

-7.73

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

-7.71

WNT7A

Homo sapiens (Human)

Protein Wnt-7a

Wnt family

NA

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

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

NA

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

NA

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

A,B

40475.5

356

0.1

50.49

7.67

1.62

-7.72

KDM5C

Homo sapiens (Human)

XE169; SMCX; Protein Xe169; Protein SmcX; Jumonji/ARID domain-containing protein 1C; JARID1C; Histone demethylase JARID1C; DXS1272E

JARID1 histone demethylase family

Paired donor oxygen oxidoreductase

Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2. Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code.

Intellectual developmental disorder, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest intellectual disability associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism. {ECO:0000269|PubMed:15586325, ECO:0000269|PubMed:16538222, ECO:0000269|PubMed:16541399, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17468742, ECO:0000269|PubMed:23356856, ECO:0000269|PubMed:25666439}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q13127; P03122

EC 1.14.11.-

3D-structure; Alternative splicing; Biological rhythms; Chromatin regulator; Dioxygenase; Disease variant; Intellectual disability; Iron; Isopeptide bond; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

50258.2

435

0.11

55.51

5.59

-13.31

-7.72

XDH

Homo sapiens (Human)

Xanthine oxidase; Xanthine dehydrogenase; XDHA

Xanthine dehydrogenase family

CH/CH(2) oxidoreductase

Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). Key enzyme in purine degradation.

Xanthinuria 1 (XAN1) [MIM:278300]: A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol. {ECO:0000269|PubMed:10844591, ECO:0000269|PubMed:11379872, ECO:0000269|PubMed:14551354, ECO:0000269|PubMed:9153281}. The disease is caused by variants affecting the gene represented in this entry.

DB00640; DB00041; DB00437; DB00993; DB00958; DB01136; DB00856; DB00515; DB00746; DB03328; DB00997; DB03516; DB12466; DB04854; DB03147; DB04335; DB01020; DB00583; DB00170; DB01033; DB00157; DB03841; DB00336; DB01250; DB05262; DB06478; DB01168; DB00339; DB00127; DB01685; DB00831

Q9Y3R0-3

NA

2Fe-2S; 3D-structure; Cytoplasm; Disease variant; Disulfide bond; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase; Peroxisome; Proteomics identification; Reference proteome; Secreted

A,B,C,D

143697

1307

0.08

37.9

8.01

7.07

-7.71

MUT

Homo sapiens (Human)

Methylmalonyl-CoA isomerase; MUT; MCM

Methylmalonyl-CoA mutase family

Intramolecular transferases

Involved in the degradation of several amino acids, odd- chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.

Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (MMAM) [MIM:251000]: An often fatal disorder of organic acid metabolism. Common clinical features include lethargy, vomiting, failure to thrive, hypotonia, neurological deficit and early death. Two forms of the disease are distinguished by the presence (mut-) or absence (mut0) of residual enzyme activity. Mut0 patients have more severe neurological manifestations of the disease than do MUT- patients. MMAM is unresponsive to vitamin B12 therapy. {ECO:0000269|PubMed:10923046, ECO:0000269|PubMed:11350191, ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:1351030, ECO:0000269|PubMed:15643616, ECO:0000269|PubMed:15781192, ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:1670635, ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493, ECO:0000269|PubMed:19588269, ECO:0000269|PubMed:1977311, ECO:0000269|PubMed:1980486, ECO:0000269|PubMed:22727635, ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:26615597, ECO:0000269|PubMed:27167370, ECO:0000269|PubMed:28101778, ECO:0000269|PubMed:7909321, ECO:0000269|PubMed:7912889, ECO:0000269|PubMed:8990001, ECO:0000269|PubMed:9285782, ECO:0000269|PubMed:9452100, ECO:0000269|PubMed:9554742}. The disease is caused by variants affecting the gene represented in this entry.

DB00115; DB00200

P42858; Q8IVH4; P22033

EC 5.4.99.2

3D-structure; Acetylation; Cobalamin; Cobalt; Cytoplasm; Direct protein sequencing; Disease variant; Isomerase; Metal-binding; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A

78878.5

714

0.07

41.69

5.94

-8.05

-7.7

KMT5C

Homo sapiens (Human)

Lysine N-methyltransferase 5C; Lysine-specific methyltransferase 5C; Suppressor of variegation 4-20 homolog 2; Su(var)4-20 homolog 2; Suv4-20h2; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KM

Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, Suvar4-20 subfamily

NA

Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4. May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).

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

Q13185

EC 2.1.1.361

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

A

27285.8

240

0.1

42.74

8.32

3.24

-7.71

AOC1

Homo sapiens (Human)

Kidney amine oxidase; KAO; Histaminase; Amiloride-binding protein; AOC1; ABP

Copper/topaquinone oxidase family

CH-NH(2) donor oxidoreductase

Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function.

Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss. {ECO:0000269|PubMed:25205112, ECO:0000269|PubMed:30237576}. The disease is caused by variants affecting the gene represented in this entry.

DB00594; DB01373; DB09130; DB03608; DB05383

Q15038; O75593; Q8IUC2; Q96HA8; Q7Z3K3; Q6ZRY4; Q01085-2; O43711; Q96K80

EC 1.4.3.22

3D-structure; Alternative splicing; Calcium; Cell membrane; Copper; Direct protein sequencing; Disulfide bond; Glycoprotein; Heparin-binding; Membrane; Metal-binding; Oxidoreductase; Proteomics identification; Reference proteome; Secreted; Signal; TPQ

A,B

162607

1425

0.13

45.72

6.76

-4.07

-7.7

AGXT

Homo sapiens (Human)

NA

AGT1;SPAT

Class-V pyridoxal-phosphate-dependent aminotransferase family

Transferase

Alanine-glyoxylate transaminase activity.Amino acid binding.Identical protein binding.Protein homodimerization activity.Protein self-association.Pyridoxal phosphate binding.Receptor binding.Serine-pyruvate transaminase activity.Transaminase activity.

Hyperoxaluria primary 1 (HP1) [MIM:259900]: An inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and progressive tissue accumulation of insoluble calcium oxalate. Affected individuals are at risk for nephrolithiasis, nephrocalcinosis and early onset end-stage renal disease. {ECO:0000269|PubMed:10394939, ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:10541294, ECO:0000269|PubMed:10862087, ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12559847, ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1301173, ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:15253729, ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:15963748, ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:1703535, ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:2039493, ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:24934730, ECO:0000269|PubMed:26149463, ECO:0000269|PubMed:8101040, ECO:0000269|PubMed:9192270, ECO:0000269|PubMed:9604803}. The disease is caused by variants affecting the gene represented in this entry.

DB08060; DB00160; DB02079; DB00145; DB04083; DB00114; DB00133

Q5BKX5-3; P21549; P0C7T5; Q9NR55; Q9H5F2; Q9UKJ5; A8MQ03; O43281-2; A1KXE4-2; Q5TD97; P49356; P53539; P49639; Q15323; O76011; O76014; Q6A162; Q07627; P60328; Q9BYR8; Q3LI67; Q8IUC2; Q9BYQ4; O60711; Q99750; Q5VZ52; P0DPK4; O43482; P50542-1; O15496; Q6ZR37; Q9NQX0; Q8HWS3; Q5W111-2; Q8WVR3; Q6DKK2

2.6.1.44; 2.6.1.51

3D-structure; Acetylation; Aminotransferase; Disease variant; Peroxisome; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A,B

84537

771

0.07

36.81

8.42

6.81

-7.69

NOS3

Homo sapiens (Human)

Nitric oxide synthase, endothelial; NOSIII; NOS,type III; NOS type III; Endothelial nitric oxide synthase; Endothelial NOS; ENOS; EC-NOS; Constitutive NOS; CNOS

NOS family

Paired donor oxygen oxidoreductase

NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.

Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm. {ECO:0000269|PubMed:11740345, ECO:0000269|PubMed:9737779}.

DB07001; DB02048; DB02911; DB02335; DB01997; DB03332; DB04534; DB07244; DB03100; DB03918; DB02207; DB03065; DB00125; DB02994; DB01833; DB00155; DB00997; DB07388; DB03974; DB02077; DB01821; DB09237; DB01110; DB03144; DB03305; DB01686; DB04559; DB02044; DB08019; DB08018; DB02027; DB02979; DB00435; DB04223; DB06154; DB03910; DB02141; DB03963; DB03707; DB02234; DB04018; DB00360; DB02589

P60709; P63010-2; Q8N6T3-3; Q9Y575-3; Q96FT7-4; Q5SZD1; Q16543; Q9UNS2; Q8IUI8; P35222; Q05193; O15287; Q08379; Q71DI3; P69905; P61978; Q12891; Q9UKT9; Q9Y2M5; Q14525; Q6DKI2; P43364-2; Q8N6F8; O94851; A4FUJ8; Q8N594; Q8IVI9; Q6X4W1-6; O15381-5; Q9NV79; Q16549; Q5T2W1; O75925; Q96I34; Q6ZMI0-5; P57052; Q9GZR2; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q7Z699; Q7Z698; P50502; Q9BR01-2; Q9NVV9; Q86WT6-2; Q9H347; P58304; Q9NZC7-5; Q9UNY5; P14079

EC 1.14.13.39

3D-structure; Alternative splicing; Calcium; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing; FAD; Flavoprotein; FMN; Golgi apparatus; Heme; Iron; Lipoprotein; Membrane; Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A,B

90790.1

803

0.11

50.67

6.03

-9.56

-7.7

FASN

Homo sapiens (Human)

Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS

NA

Acyltransferase

Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.

Glycine encephalopathy 2 (GCE2) [MIM:620398]: A form of glycine encephalopathy, a metabolic disorder characterized by a high concentration of glycine in the body fluids. Affected individuals typically have severe neurological symptoms, including seizure, lethargy, and muscular hypotonia soon after birth. Most of them die within the neonatal period. Atypical cases have later disease onset and less severely affected psychomotor development. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. The disease is caused by variants affecting the gene represented in this entry.

DB01034; DB01083

Q15848; Q16665; P42858; Q8IV20; Q8TBB1; PRO_0000045603 [Q99IB8]

EC 2.3.1.85

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; S-nitrosylation; Transferase; Ubl conjugation

A

30174.9

275

0.09

43.28

5.92

-5.4

-7.69

RIDA

Homo sapiens (Human)

NA

HRSP12

RutC family

Translation

Deaminase activity.Endoribonuclease activity, producing 3'-phosphomonoesters.Long-chain fatty acid binding.Platinum binding.Protein homodimerization activity.RNA binding.Transition metal ion binding.Xenon atom binding.

Congenital bile acid synthesis defect 2 (CBAS2) [MIM:235555]: A condition characterized by jaundice, intrahepatic cholestasis and hepatic failure. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine. {ECO:0000269|PubMed:12970144, ECO:0000269|PubMed:15030995, ECO:0000269|PubMed:19175828, ECO:0000269|PubMed:20522910}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q8N9N5-2

3.5.99.10

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase; Lipid metabolism; Mitochondrion; Nucleus; Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; RNA-binding

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

42624.3

404

0.07

36.76

8.99

5.46

-7.69