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
• 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.

• Inborn_genetic_diseases (61 variants)
• Neurodegeneration,_childhood-onset,_stress-induced,_with_variable_ataxia_and_seizures (25 variants)
• not_provided (10 variants)
• ADPRS-related_disorder (3 variants)
• Bilateral_sensorineural_hearing_impairment (1 variants)
• ADPRHL2-related_disorder (1 variants)
• Progressive_sensorineural_hearing_impairment (1 variants)
• Loss_of_consciousness (1 variants)
• Axial_hypotonia (1 variants)
• Progressive_gait_ataxia (1 variants)
• Atypical_absence_seizure (1 variants)
• Abdominal_distention (1 variants)
• Delayed_speech_and_language_development (1 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. These statistics are base on transcript: NM_000017825.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4	1	6
missense	1	5	62	5		73
nonsense	1	4				5
start loss						0
frameshift	4	2	1			7
splice donor/acceptor (+/-2bp)						0
Total	6	11	64	9	1

Highest pathogenic variant AF is 0.000086735

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