ADPRS (ADP-ribosylserine hydrolase)

Gene

• Entrez ID: 54936
• Gene name: ADP-ribosylserine hydrolase
• Gene symbol: ADPRS
• Synonyms (NCBI Gene): ADPRHL2, ARH3, CONDSIAS
• Chromosome: 1
• Chromosome location: 1p34.3
• Summary: This gene encodes a member of the ADP-ribosylglycohydrolase family. The encoded enzyme catalyzes the removal of ADP-ribose from ADP-ribosylated proteins. This enzyme localizes to the mitochondria, in addition to the nucleus and cytoplasm.[provided by RefS

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200626873	C>T	Pathogenic	Missense variant, coding sequence variant
rs201735454	T>C,G	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs368433666	C>G,T	Likely-pathogenic	5 prime UTR variant, coding sequence variant, missense variant, stop gained
rs1557732234	G>A	Pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant
rs1557733311	A>C	Pathogenic	Intron variant, coding sequence variant, missense variant
rs1557733367	G>-	Pathogenic	Intron variant, coding sequence variant, frameshift variant
rs1557733597	TGCCC>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs1557734377	C>T	Pathogenic	Stop gained, coding sequence variant
rs1570008399	AG>-	Likely-pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant
rs1570012058	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1570013257	GAT>-	Likely-pathogenic	Coding sequence variant, inframe indel

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000287	Function	Magnesium ion binding	IDA	30045870, 33894202
GO:0004553	Function	Hydrolase activity, hydrolyzing O-glycosyl compounds	IDA	30045870
GO:0004649	Function	Poly(ADP-ribose) glycohydrolase activity	IDA	17075046, 30830864, 33894202, 34019811, 34479984
GO:0004649	Function	Poly(ADP-ribose) glycohydrolase activity	IEA
GO:0004649	Function	Poly(ADP-ribose) glycohydrolase activity	IMP	33769608, 34321462
GO:0004649	Function	Poly(ADP-ribose) glycohydrolase activity	TAS
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	30045870, 34479984
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IDA	34479984
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	34479984
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006281	Process	DNA repair	IEA
GO:0006281	Process	DNA repair	IMP	30045870
GO:0006287	Process	Base-excision repair, gap-filling	TAS
GO:0006974	Process	DNA damage response	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0016787	Function	Hydrolase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060546	Process	Negative regulation of necroptotic process	IEA
GO:0060546	Process	Negative regulation of necroptotic process	ISS
GO:0061463	Function	O-acetyl-ADP-ribose deacetylase activity	IDA	17075046, 21498885
GO:0071451	Process	Cellular response to superoxide	IEA
GO:0071451	Process	Cellular response to superoxide	IEA
GO:0071451	Process	Cellular response to superoxide	IMP	30401461
GO:0090734	Component	Site of DNA damage	IDA	30045870
GO:0140290	Process	Peptidyl-serine ADP-deribosylation	IDA	28650317, 29234005, 33186521
GO:0140290	Process	Peptidyl-serine ADP-deribosylation	IEA
GO:0140292	Function	ADP-ribosylserine hydrolase activity	IDA	28650317, 29234005, 33186521, 34625544, 37268618
GO:0140292	Function	ADP-ribosylserine hydrolase activity	IEA

Other IDs

• MIM: 610624
• HGNC: 21304
• e!Ensembl: ENSG00000116863

Protein

• UniProt ID: Q9NX46
• Protein name: ADP-ribosylhydrolase ARH3 (ADP-ribose glycohydrolase ARH3) (ADP-ribosylhydrolase 3) (O-acetyl-ADP-ribose deacetylase ARH3) (EC 3.5.1.-) (Poly(ADP-ribose) glycohydrolase ARH3) (EC 3.2.1.143) ([Protein ADP-ribosylarginine] hydrolase-like protein 2) ([Protei
• Protein function: ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribos
• PDB: 2FOZ, 2FP0, 2G4K, 5ZQY, 6D36, 6D3A, 7AKR, 7AKS, 7ARW, 7L9F, 7L9H, 7L9I
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03747	ADP_ribosyl_GH	25 → 338	ADP-ribosylglycohydrolase	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous (PubMed:16278211). Expressed in skin fibroblasts (PubMed:30830864). {ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:30830864}.
• Sequence:

  MAAAAMAAAAGGGAGAARSLSRFRGCLAGALLGDCVGSFYEAHDTVDLTSVLRHVQSLEP
  DPGTPGSERTEALYYTDDTAMARALVQSLLAKEAFDEVDMAHRFAQEYKKDPDRGYGAGV
  VTVFKKLLNPKCRDVFEPARAQFNGKGSYGNGGAMRVAGISLAYSSVQDVQKFARLSAQL
  THASSLGYNGAILQALAVHLALQGESSSEHFLKQLLGHMEDLEGDAQSVLDARELGMEER
  PYSSRLKKIGELLDQASVTREEVVSELGNGIAAFESVPTAIYCFLRCMEPDPEIPSAFNS
  LQRTLIYSISLGGDTDTIATMAGAIAGAYYGMDQVPESWQQSCEGYEETDILAQSLHRVF
  QKS

• Sequence length: 363

Pathways

KEGG:

Base excision repair

Reactome:

POLB-Dependent Long Patch Base Excision Repair

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
ADPRHL2-related disorder	Pathogenic	rs768832709	RCV001825182	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ADPRS-related disorder	Likely pathogenic; Pathogenic	rs201735454	RCV005870837	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Likely pathogenic; Pathogenic	rs2124055267, rs2524677372, rs2524677445, rs2524684835, rs1557734377, rs368433666, rs1557733311, rs1557733597, rs200626873, rs1557732234, rs201735454, rs1557733367, rs1570012058, rs1570008399, rs1570013257	RCV002226934 RCV003314270 RCV003334461 RCV003485009 RCV000721139 RCV000721140 RCV000721141 RCV000721142 RCV000721143 RCV000721144 RCV000735981 RCV000735982 RCV000986287 RCV000991356 RCV000995689	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATYPICAL ABSENCE SEIZURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD-ONSET STRESS-INDUCED NEURODEGENERATIVE ATAXIA-SEIZURE SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	34344401	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	30401461, 34479984	Associate	★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	30830864		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	30401461, 34479984	Associate	★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	GENOMICS_ENGLAND_DG	30100084		★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	30401461		★☆☆☆☆ Found in Text Mining only
HYPERCHOLESTEROLEMIA, AUTOSOMAL RECESSIVE	Hypercholesterolemia	BEFREE	19477448		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	30100084		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	23736962		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	23736962		★☆☆☆☆ Found in Text Mining only
NEURODEGENERATION, CHILDHOOD-ONSET, STRESS-INDUCED, WITH VARIABLE ATAXIA AND SEIZURES	Neurodegenerative Disorders with variable ataxia and seizures	UNIPROT_DG	30100084, 30401461		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEGENERATION, CHILDHOOD-ONSET, STRESS-INDUCED, WITH VARIABLE ATAXIA AND SEIZURES	Neurodegenerative Disorders with variable ataxia and seizures	CLINVAR_DG	30401461		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEGENERATION, CHILDHOOD-ONSET, STRESS-INDUCED, WITH VARIABLE ATAXIA AND SEIZURES	Neurodegenerative Disorders with variable ataxia and seizures	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	30401461, 32636369	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30401461		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	30401461	Associate	★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	30401461	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only