PARP4

Chr 13

poly(ADP-ribose) polymerase family member 4

Also known as: ADPRTL1, ARTD4, PARP-4, PARPL, PH5P, VAULT3, VPARP, VWA5C

NCBI Gene: 143ENSG00000102699UniProt: Q9UKK3OMIM: 607519

This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which catalyzes mono-ADP-ribosylation of target proteins and lacks the DNA-binding domain found in classical poly(ADP-ribose) polymerases. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain malformations. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.84
Clinical Summary— PARP4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 234 VUS of 374 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
0.84LOEUF
pLI 0.000
Z-score 2.78
OE 0.67 (0.54–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.99 (0.93–1.04)
878 obs / 888.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.54–0.84)
0≤0.351.4
Missense OE0.99 (0.93–1.04)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 55 / 82.2Missense obs/exp: 878 / 888.6Syn Z: -0.85
DN
0.76top 25%
GOF
0.6052th %ile
LOF
0.2092th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic2
VUS234
Likely Benign19
Benign12
Conflicting2
33
Pathogenic
2
Likely Pathogenic
234
VUS
19
Likely Benign
12
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
2
0
2
VUS
0
225
9
0
234
Likely Benign
0
10
3
6
19
Benign
0
4
4
4
12
Conflicting
—2
Total02395110302

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

View in ClinVar →

Protein Context — Lollipop Plot

PARP4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients