ADPRS

ADP-ribosylserine hydrolase

Basic information

Region (hg38): 1:36088892-36093932

Previous symbols: [ "ADPRHL2" ]

Links

ENSG00000116863 ∙ NCBI:54936 ∙ OMIM:610624 ∙ HGNC:21304 ∙ Uniprot:Q9NX46 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	AR	General	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	Neurologic	30100084; 30401461

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADPRS gene.

• Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures (3 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADPRS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense	1	3	31	3		38
nonsense		3				3
start loss						0
frameshift	3	1				4
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	4	8	32	7	1

Highest pathogenic variant AF is 0.000105

Variants in ADPRS

This is a list of pathogenic ClinVar variants found in the ADPRS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-36088910-C-CGCAGCGGCGATGGCG		Inborn genetic diseases	Uncertain significance (Jun 25, 2021)
1-36088926-G-A		Inborn genetic diseases	Likely benign (Mar 11, 2024)
1-36088927-C-T		Inborn genetic diseases	Likely benign (Oct 30, 2023)
1-36088930-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
1-36088936-G-A		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
1-36088940-A-G			Likely benign (Jul 01, 2022)
1-36088951-C-G		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
1-36088957-G-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
1-36089004-G-A		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Pathogenic (Nov 08, 2018)
1-36089005-A-G		Inborn genetic diseases	Uncertain significance (Jul 28, 2021)
1-36089029-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
1-36089040-G-C		Inborn genetic diseases	Uncertain significance (Apr 30, 2021)
1-36089040-G-T		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Uncertain significance (Jan 23, 2020)
1-36089049-AC-A		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Pathogenic (-)
1-36089070-C-T		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Likely pathogenic (Oct 06, 2023)
1-36089070-CAG-C		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Likely pathogenic (Jun 20, 2019)
1-36091266-C-T		ADPRS-related disorder	Benign (Mar 20, 2019)
1-36091267-A-C		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Pathogenic/Likely pathogenic (Sep 30, 2020)
1-36091270-G-T		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Uncertain significance (Mar 29, 2024)
1-36091274-T-A		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Uncertain significance (Mar 29, 2024)
1-36091307-A-G		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
1-36091320-C-T			Likely benign (Jun 01, 2022)
1-36091322-AG-A		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Pathogenic (Jan 09, 2019)
1-36091333-G-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
1-36091625-C-T		Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures	Likely pathogenic (May 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADPRS	protein_coding	protein_coding	ENST00000373178	6	5058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000575	0.906	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.348	186	200	0.931	0.0000110	2325
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000988	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000497	0.000489

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.252
• hipred: N
• hipred_score: 0.248
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adprhl2

Gene ontology

• Biological process: cellular response to superoxide
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;nuclear body
• Molecular function: poly(ADP-ribose) glycohydrolase activity;metal ion binding