HPF1
Chr 4histone PARylation factor 1
Also known as: C4orf27
The HPF1 protein serves as a cofactor that confers serine specificity on PARP1 and PARP2 enzymes, enabling serine ADP-ribosylation of target proteins during DNA double-strand break repair and chromatin remodeling. Mutations in HPF1 cause neurodevelopmental disorders with intellectual disability, seizures, and brain malformations, following an autosomal recessive inheritance pattern. The gene is highly intolerant to loss-of-function variants, indicating that complete loss of HPF1 function has severe consequences for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
71 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 52 |
Likely Pathogenic | — | — | — | — | 3 |
VUS | — | — | — | — | 7 |
Likely Benign | — | — | — | — | 2 |
Benign | — | — | — | — | 0 |
| Total | — | 64 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HPF1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools