PARP10

Chr 8

poly(ADP-ribose) polymerase family member 10

Also known as: ARTD10

NCBI Gene: 84875 ENSG00000178685 UniProt: Q53GL7 OMIM: 609564

PARP10 encodes an ADP-ribosyltransferase that catalyzes mono-ADP-ribosylation of target proteins, regulates GSK3B kinase activity, and participates in DNA damage response through interaction with PCNA. The gene shows relatively low constraint to loss-of-function variation (LOEUF 0.74), but no confirmed Mendelian diseases have been associated with PARP10 mutations to date.

OMIM ResearchSummary from RefSeq, UniProt

Poly(ADP-ribose) polymerases (PARPs), such as PARP10, regulate gene transcription by altering chromatin organization by adding ADP-ribose to histones. PARPs can also function as transcriptional cofactors (Yu et al., 2005 [PubMed 15674325]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.74

Clinical Summary— PARP10

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 212 VUS of 281 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.82

OE 0.50 (0.35–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.55Z-score

OE missense 0.83 (0.77–0.89)

532 obs / 642.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.35–0.74)

0≤0.351.4

Missense OE?0.83 (0.77–0.89)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 19 / 37.7Missense obs/exp: 532 / 642.6Syn Z: 1.19

This gene — mechanism propensity

0.6358th %ile

GOF

0.72top 25%

LOF

0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

281 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS212

Likely Benign26

Benign1

Conflicting2

Likely Pathogenic

212

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	212	0	0	212
Likely Benign	0	24	0	2	26
Benign	0	0	0	1	1
Conflicting	—				2
Total	1	236	0	3	242

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

View in ClinVar →

62 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap PARP10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →