ADPRS

Chr 1AR

ADP-ribosylserine hydrolase

Also known as: ADPRHL2, ARH3, CONDSIAS

NCBI Gene: 54936ENSG00000116863UniProt: Q9NX46

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]

Primary Disease Associations & Inheritance

Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizuresMIM #618170
AR
113
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADPRS
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 75 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.001
Z-score 1.49
OE 0.55 (0.31–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.35Z-score
OE missense 0.93 (0.82–1.05)
186 obs / 199.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.31–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.82–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 7 / 12.7Missense obs/exp: 186 / 199.9Syn Z: -1.07

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic13
VUS75
Likely Benign11
Benign1
Conflicting1
12
Pathogenic
13
Likely Pathogenic
75
VUS
11
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
7
0
12
Likely Pathogenic
2
5
6
0
13
VUS
1
66
7
1
75
Likely Benign
0
7
0
4
11
Benign
0
0
0
1
1
Conflicting
—1
Total779206113

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADPRS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ADPRS-related neurodegeneration with developmental delay ataxia and axonal neuropathy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

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

MIM #618170

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification.
D'Aoust T et al.·Alzheimers Dement
2025
An ADPRS variant disrupts ARH3 stability and subcellular localization in children with neurodegeneration and respiratory failure.
Bannister M et al.·HGG Adv
2025Case report
Use of an Alzheimer's disease polygenic risk score to identify mild cognitive impairment in adults in their 50s.
Logue MW et al.·Mol Psychiatry
2019
Phenotypic Diversity in Stress-induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures: Novel Associations with Parkinsonism, Icthyosis and Cataract.
Nandana J et al.·Cerebellum
2025Case report
The impact of polygenic risk for alzheimer's disease on neurotransmitter-related grey matter atrophy in the alzheimer continuum.
Manca R et al.·Neurol Sci
2025
Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies.
van der Lee SJ et al.·J Alzheimers Dis
2021
Expanding the Spectrum of Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures (CONDSIAS).
Lindskov FO et al.·Cerebellum
2024Case report
The neural signatures of psychoses in Alzheimer's disease: a neuroimaging genetics approach.
Manca R et al.·Eur Arch Psychiatry Clin Neurosci
2023
Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease.
Murray AN et al.·Neurobiol Aging
2021
Genetic risk for Alzheimer's dementia predicts motor deficits through multi-omic systems in older adults.
Tasaki S et al.·Transl Psychiatry
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools