MT-CO2

Homo sapiens (Human)

NA

MTCO2;COXII;COII;COX2

Cytochrome c oxidase subunit 2 family

Immune system

Copper ion binding.Cytochrome-c oxidase activity.

Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:10486321}. The disease is caused by variants affecting the gene represented in this entry.

DB02659; DB04464; DB05412

Q9NZ94-2; P49281-3

7.1.1.9

3D-structure; Copper; Disease variant; Electron transport; Magnesium; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; Proteomics identification; Reference proteome; Respiratory chain; Translocase; Transmembrane; Transmembrane helix; Transport

C

21687.9

189

0.11

38

5.68

-3.26

-5.37

VDR

Homo sapiens (Human)

Vitamin D(3) receptor; Nuclear vitamin D receptor; Nuclear receptor subfamily 1 group I member 1; NR1I1; 1,25-dihydroxyvitamin D3 receptor

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.

Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets. {ECO:0000269|PubMed:1652893, ECO:0000269|PubMed:17970811, ECO:0000269|PubMed:2177843, ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:7828346, ECO:0000269|PubMed:8106618, ECO:0000269|PubMed:8381803, ECO:0000269|PubMed:8392085, ECO:0000269|PubMed:8675579, ECO:0000269|PubMed:8961271, ECO:0000269|PubMed:9005998}. The disease is caused by variants affecting the gene represented in this entry.

DB07530; DB08742; DB01436; DB04891; DB00146; DB02300; DB00136; DB00169; DB04540; DB05024; DB11672; DB14635; DB01070; DB06410; DB05295; DB06194; DB00153; DB04796; DB03451; DB00910; DB04258; DB11094

P35222; Q09472; Q15648; P50222; Q15788; P26045; P19793; Q13573; Q13501; P04637; Q15645; Q9JLI4; P28700; X5D778; Q96HA8; Q01804; Q96S38; P48443

NA

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

A

28781

254

0.07

47.69

6.15

-3.44

-5.37

TAT

Homo sapiens (Human)

NA

NA

Class-I pyridoxal-phosphate-dependent aminotransferase family

Transferase

Amino acid binding.L-phenylalanine:2-oxoglutarate aminotransferase activity.L-tyrosine:2-oxoglutarate aminotransferase activity.Pyridoxal phosphate binding.

Tyrosinemia 2 (TYRSN2) [MIM:276600]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and intellectual disability. {ECO:0000269|PubMed:1357662}. The disease is caused by variants affecting the gene represented in this entry.

DB00142; DB00120; DB00114; DB00135

P15104; P28799; P28799-2; P17735; Q05086; Q05086-3

2.6.1.5

3D-structure; Acetylation; Aminotransferase; Disease variant; Intellectual disability; Palmoplantar keratoderma; Phenylalanine catabolism; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase; Tyrosine catabolism

A,B

42209.5

380

0.08

51.79

5.29

-10.66

-5.37

ACHE

Homo sapiens (Human)

YT; N-ACHE; ARACHE

Type-B carboxylesterase/lipase family

Carboxylic ester hydrolase

Role in neuronal apoptosis. Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.

Phosphoribosylaminoimidazole carboxylase deficiency (PAICSD) [MIM:619859]: An autosomal recessive inborn error of purine metabolism, clinically characterized by multiple congenital anomalies and early neonatal death. {ECO:0000269|PubMed:31600779}. The disease is caused by variants affecting the gene represented in this entry.

DB07846; DB02673; DB04617; DB04614; DB04615; DB07756; DB07701; DB02404; DB03814; DB08615; DB02343; DB02226; DB03005; DB04114; DB03128; DB01122; DB03283; DB00411; DB00122; DB14006; DB01245; DB00944; DB08357; DB08996; DB00449; DB00843; DB01010; DB01364; DB00898; DB00674; DB00483; DB06525; DB04864; DB03348; DB07555; DB00677; DB04924; DB03359; DB00358; DB00940; DB02825; DB02845; DB08167; DB04021; DB00805; DB01805; DB03740; DB04556; DB01400; DB04892; DB00981; DB00733; DB02166; DB00545; DB00863; DB00989; DB00382; DB04616; DB12816; DB01199; DB13503; DB04859

Q9Y215; P06733; P63244

EC 3.1.1.7

3D-structure; Alternative splicing; Blood group antigen; Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Neurotransmitter degradation; Nucleus; Proteomics identification; Reference proteome; Secreted; Serine esterase; Signal; Synapse

A,B

58804.1

537

0.11

40.85

5.73

-8.18

-5.37

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

-5.37

camC

Pseudomonas putida (Arthrobacter siderocapsulatus)

NA

cyp101

Cytochrome P450 family

Oxidoreductase

Camphor 5-monooxygenase activity.Heme binding.Iron ion binding.

Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070, ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614]: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. {ECO:0000269|PubMed:25986071}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. {ECO:0000269|PubMed:28842795}. The disease is caused by variants affecting the gene represented in this entry.

DB03836; DB02617; DB02817; DB03627; DB04032; DB03031; DB02125; DB04501; DB01744; DB01663; DB01011; DB01703; DB01826; DB03540; DB02851

P00259

1.14.15.1

3D-structure; Cytoplasm; Direct protein sequencing; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase

A

45446.3

405

0.08

45.33

5.23

-16.08

-5.36

CHD1

Homo sapiens (Human)

NA

NA

SNF2/RAD54 helicase family

Dna binding protein / viral protein

ATP binding.ATP-dependent DNA helicase activity.DNA binding.Methylated histone binding.

Pilarowski-Bjornsson syndrome (PILBOS) [MIM:617682]: An autosomal dominant disorder characterized by developmental delay, speech apraxia, intellectual disability, autism, and facial dysmorphic features. Some patients may have seizures. {ECO:0000269|PubMed:28866611}. The disease is caused by variants affecting the gene represented in this entry.

NA

O60341-1; B2BUF1; P28799; O76024

3.6.4.12

3D-structure; Alternative splicing; ATP-binding; Chromatin regulator; Cytoplasm; Disease variant; DNA-binding; Helicase; Hydrolase; Intellectual disability; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation

A

20969.1

180

0.12

46.35

5.88

-2.83

-5.37

dld

Escherichia coli (strain K12)

NA

JW2121;b2133

Quinone-dependent D-lactate dehydrogenase family

Oxidoreductase

(R)-2-hydroxyglutarate dehydrogenase activity.D-lactate dehydrogenase (cytochrome) activity.Electron carrier activity.FAD binding.Flavin adenine dinucleotide binding.NAD binding.Oxidoreductase activity, acting on the CH-OH group of donors, quinone or similar compound as acceptor.Quinone 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.

DB03147; DB00756

NA

1.1.5.12

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; FAD; Flavoprotein; Membrane; Oxidoreductase; Quinone; Reference proteome

A,B

56475.2

502

0.09

32.5

5.97

-10.38

-5.36

GSTP1

Homo sapiens (Human)

GSTP11; GSTP1-1; GST3; GST classpi; GST class-pi; FAEES3

GST superfamily, Pi family

Alkyl aryl transferase

Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB01834; DB03814; DB00316; DB14001; DB00321; DB01008; DB04972; DB00958; DB00291; DB02633; DB00515; DB01242; DB00363; DB11672; DB14635; DB14002; DB03619; DB11831; DB00903; DB00773; DB06246; DB05460; DB00143; DB03310; DB03003; DB13014; DB00526; DB14924; DB08370; DB03686; DB04132; DB01915; DB07849; DB00197; DB00163

Q6UY14-3; Q92624; Q9BWT7; A8MQ03; Q9NRD0; Q5TD97; P49639; Q15323; Q14525; O76011; P78385; Q07627; Q8IUG1; P60409; P60411; Q9BYR8; Q9BYR6; Q3LI66; Q9P2M1; Q5JR59-3; Q7Z3S9; P0DPK4; P22735; Q12933; Q8N720

EC 2.5.1.18

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; Mitochondrion; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transferase

A,B

46333.6

417

0.1

30.67

5.44

-5.73

-5.36

ACADM

Homo sapiens (Human)

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Acyl-CoA dehydrogenase activity.Flavin adenine dinucleotide binding.Identical protein binding.Medium-chain-acyl-CoA dehydrogenase activity.

Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. The disease is caused by variants affecting the gene represented in this entry.

DB03415; DB03147; DB02910

PRO_0000000502 [P11310]

1.3.8.7

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Disease variant; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A,B,C,D

85080.3

773

0.09

30.55

5.71

-7.7

-5.36

ASS1

Homo sapiens (Human)

NA

ASS

Argininosuccinate synthase family, Type 1 subfamily

Ligase

Amino acid binding.Argininosuccinate synthase activity.ATP binding.Identical protein binding.RNA binding.

Citrullinemia 1 (CTLN1) [MIM:215700]: The classic form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. It is a disorder of the urea cycle, usually manifesting in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder form can develop later in childhood or adulthood. {ECO:0000269|PubMed:11708871, ECO:0000269|PubMed:11941481, ECO:0000269|PubMed:12815590, ECO:0000269|PubMed:14680976, ECO:0000269|PubMed:15863597, ECO:0000269|PubMed:16475226, ECO:0000269|PubMed:18473344, ECO:0000269|PubMed:19006241, ECO:0000269|PubMed:1943692, ECO:0000269|PubMed:2358466, ECO:0000269|PubMed:23611581, ECO:0000269|PubMed:24889030, ECO:0000269|PubMed:25179242, ECO:0000269|PubMed:27287393, ECO:0000269|PubMed:28111830, ECO:0000269|PubMed:7977368}. The disease is caused by variants affecting the gene represented in this entry.

DB00125; DB00128; DB00171; DB00155

P10398; P00966; Q9HBL8; Q9NVM4

6.3.4.5

3D-structure; Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; Ligase; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Urea cycle

A

41098.8

364

0.1

36.56

8.4

3.55

-5.36

DBH

Homo sapiens (Human)

NA

NA

Copper type II ascorbate-dependent monooxygenase family

Oxidoreductase

Catalytic activity.Copper ion binding.Dopamine beta-monooxygenase activity.L-ascorbic acid binding.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB00126; DB06774; DB09130; DB05394; DB00822; DB00988; DB00968; DB00550

P00352; P63010-2; Q04656; Q8WUW1; Q9UNS2; Q71DI3; P61978; Q9Y2M5; Q92876; P08727; Q14693; P0DPK4; Q6GQQ9-2; P27986-2; Q9ULX5; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q86WT6-2

1.14.17.1

3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C

A,B

123694

1094

0.1

51.85

5.84

-24.5

-5.36

PROC

Homo sapiens (Human)

Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; PROC; Blood coagulation factor XIV; Autoprothrombin IIA; Anticoagulant protein C; Activation peptide

Peptidase S1 family

Peptidase

Protein C is avitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.

Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency. {ECO:0000269|PubMed:1301959, ECO:0000269|PubMed:1347706, ECO:0000269|PubMed:1511989, ECO:0000269|PubMed:1868249, ECO:0000269|PubMed:2437584, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:25748729, ECO:0000269|PubMed:2602169, ECO:0000269|PubMed:7792728, ECO:0000269|PubMed:7865674, ECO:0000269|PubMed:8292730, ECO:0000269|PubMed:8398832, ECO:0000269|PubMed:8499568, ECO:0000269|PubMed:8560401, ECO:0000269|PubMed:8829639, ECO:0000269|PubMed:9798967}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. {ECO:0000269|PubMed:1511988, ECO:0000269|PubMed:1593215, ECO:0000269|PubMed:1611081, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:7841323, ECO:0000269|PubMed:7841324, ECO:0000269|PubMed:7878626}. The disease is caused by variants affecting the gene represented in this entry.

DB13192; DB00025; DB09131; DB09332; DB13998; DB00170; DB13999; DB13149; DB00464; DB14738

A8MQ03; P51511

EC 3.4.21.69

3D-structure; Alternative splicing; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Endoplasmic reticulum; Gamma-carboxyglutamic acid; Glycoprotein; Golgi apparatus; Hemostasis; Hydrolase; Hydroxylation; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Thrombophilia; Zymogen

C,D

45326

411

0.12

40.68

7.07

0.29

-5.35

AKR1B1

Homo sapiens (Human)

Aldehyde reductase; AKR1B1

Aldo/keto reductase family

Short-chain dehydrogenases reductase

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.

Glutamine deficiency, congenital (GLND) [MIM:610015]: An autosomal recessive disorder characterized by variable brain malformations, encephalopathy, severe developmental delay, seizures, and decreased glutamine levels in bodily fluids. Death in early infancy may occur. {ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 116 (DEE116) [MIM:620806]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE116 is autosomal dominant form characterized by severe developmental delay, seizures, and white matter abnormalities. {ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry. DEE116 is caused by variants that disrupt the canonical translation start codon in GLUL resulting in initiation of translation at Met-18 (PubMed:38579670). The resulting protein is enzymatically competent but insensitive to negative feedback regulation via glutamine-induced degradation. {ECO:0000269|PubMed:38579670}.

DB07028; DB07030; DB07450; DB02101; DB08449; DB08000; DB07139; DB07498; DB02007; DB02020; DB11859; DB02994; DB04272; DB07187; DB00694; DB00997; DB06246; DB01039; DB02021; DB16707; DB00143; DB02834; DB08084; DB01689; DB07063; DB06077; DB02518; DB00157; DB03461; DB05383; DB05533; DB05327; DB02712; DB00605; DB02383; DB02132; DB08772; DB07093; DB07999; DB08098

Q9BUY7

EC 1.1.1.300

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome

A

35447.6

313

0.09

36.41

7.1

0.26

-5.36

POLA1

Homo sapiens (Human)

POLA; DNA polymerase alpha catalytic subunit p180; DNA polymerase alpha catalytic subunit

DNA polymerase type-B family

Kinase

During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses. Plays an essential role in the initiation of DNA replication.

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.

DB00242; DB00631; DB01073; DB01280

P27694; P10193; P03070

EC 2.7.7.7

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Disease variant; DNA replication; DNA-binding; DNA-directed DNA polymerase; Dwarfism; Host-virus interaction; Intellectual disability; Metal-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Zinc; Zinc-finger

A

24505.6

212

0.09

43.56

9.02

4.85

-5.35

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

-5.36

penA

Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

NA

spr1517;pbp2b

Transpeptidase family

Peptide binding protein

Penicillin binding.

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.

DB01163; DB00415; DB08795; DB01140; DB00456; DB01066; DB00493; DB01331; DB01212; DB00567; DB03313; DB00485; DB00739; DB01603; DB00607; DB00713; DB00319

NA

NA

3D-structure; Antibiotic resistance; Cell membrane; Cell shape; Cell wall biogenesis/degradation; Membrane; Peptidoglycan synthesis; Reference proteome; Transmembrane; Transmembrane helix

A,B,C

65444.4

607

0.08

30.15

4.95

-20.68

-5.36

ASL

Homo sapiens (Human)

NA

NA

Lyase 1 family, Argininosuccinate lyase subfamily

Lyase

Argininosuccinate lyase activity.Identical protein binding.

Argininosuccinic aciduria (ARGINSA) [MIM:207900]: An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness. {ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433, ECO:0000269|PubMed:12408190, ECO:0000269|PubMed:1705937, ECO:0000269|PubMed:17326097, ECO:0000269|PubMed:19703900, ECO:0000269|PubMed:22081021, ECO:0000269|PubMed:2263616, ECO:0000269|PubMed:24166829, ECO:0000269|PubMed:9045711}. The disease is caused by variants affecting the gene represented in this entry. The phenotype heterogeneity among patients is associated with interallelic complementation resulting in either complete loss of activity or partial regeneration of functional active sites in the heterotetrameric mutant protein. {ECO:0000269|PubMed:11747433}.

DB03814; DB00125; DB02267

P04424; Q9BTE3-2; Q96HA8; O75382

4.3.2.1

3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis; Arginine biosynthesis; Disease variant; Lyase; Proteomics identification; Reference proteome; Urea cycle

A,B

51364.1

459

0.08

35.82

6.66

-1.25

-5.36

ADA

Plasmodium vivax (strain Salvador I)

NA

PVX_111245

Metallo-dependent hydrolases superfamily, Adenosine and AMP deaminases family

NA

Catalyzes the hydrolytic deamination of adenosine to produce inosine (PubMed:19728741). Unlike mammalian adenosine deaminases, also catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI) (PubMed:19728741). Plays an essential role in the purine salvage pathway which allows the parasite to use host cell purines for the synthesis of nucleic acids (PubMed:19728741). {ECO:0000269|PubMed:19728741}."

NA

NA

NA

3.5.4.31; 3.5.4.4

3D-structure; Hydrolase; Metal-binding; Purine salvage; Reference proteome; Zinc

A

41950.8

364

0.11

27.19

5.49

-13.73

-5.36

MMP2

Homo sapiens (Human)

NA

CLG4A

Peptidase M10A family

Hydrolase / hydrolase inhibitor

Metalloendopeptidase activity.Metallopeptidase activity.Serine-type endopeptidase activity.Zinc ion binding.

Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. {ECO:0000269|PubMed:11431697, ECO:0000269|PubMed:15691365, ECO:0000269|PubMed:16542393}. The disease is caused by variants affecting the gene represented in this entry.

DB01197; DB06423; DB04866; DB00786; DB05387; DB12843; DB01630

P05067; PRO_0000000092 [P05067]; PRO_0000000093 [P05067]; P20908; Q8NBP7; Q04864-2; Q8IX30; P16035

3.4.24.24

3D-structure; Alternative splicing; Angiogenesis; Autocatalytic cleavage; Calcium; Collagen degradation; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Mitochondrion; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen

A

19623.6

176

0.14

15.48

4.84

-10.61

-5.35