ADPRS

protein-coding

ADP-ribosylserine hydrolase

Gene 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 RefSeq, Feb 2009]

Previous symbols:

ADPRHL2

MANE transcript

NM_017825.3

Inheritance

ClinVar variants

P:23U:72B:21

Top phenotype

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:36,088,892-36,093,932

External References & Databases

Ensembl (ENSG00000116863)

Transcript & Mutation Effects

hg38 • Region Span ~5.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100095

Submitter: Labcorp Genetics (formerly Invitae)

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100095

Submitter: PanelApp Australia

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100095

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30100084; 30401461

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADPRS variants in ClinVar

15 Conditions Cataloged

Inborn genetic diseasesTotal: 69

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresTotal: 32

not specifiedTotal: 17

not providedTotal: 16

ADPRS-related disorderTotal: 5

ADPRHL2-related disorderTotal: 2

Progressive sensorineural hearing impairmentTotal: 1

Atypical absence seizureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017825.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	12 clinvar	1 clinvar	14
missense	1 clinvar	6 clinvar	67 clinvar	8 clinvar		82
nonsense	4 clinvar	4 clinvar	1 clinvar			9
start loss						0
frameshift	6 clinvar	2 clinvar	2 clinvar			10
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	11	12	72	20	1	116

Highest pathogenic variant AF is 0.000086734995

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017825.3	RefSeq	NP_060295.1	6	MANE Select
ENST00000373178.5	Ensembl	ENSP00000362273.4	6	MANE Select
ENST00000896939.1	Ensembl	ENSP00000566998.1	6	Standard
ENST00000896939.2	Ensembl	ENSP00000566998.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to superoxide

Molecular Function

poly(ADP-ribose) glycohydrolase activity
metal ion binding

Cellular Component

nucleus
nucleoplasm
mitochondrion
mitochondrial matrix
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373178
Coding exons: 6
Length: 5058
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.348	186	200	0.931	0.0000110	2325
Missense (PolyPhen)		54	74.92	0.72076		842
Synonymous	-1.07	97	84.5	1.15	0.00000492	756
Loss of Function	1.49	7	12.7	0.550	5.41e-7	164

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism may be required for maintenance of the normal function of neuronal cells. Generates ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP- ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds. Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3 is the only PAR hydrolyzing enzyme in mitochondria. {ECO:0000269|PubMed:16278211}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.547
RVIS EVS: -0.58
RVIS percentile EVS: 18.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.968

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium