HPF1

Chr 4

histone PARylation factor 1

Also known as: C4orf27

NCBI Gene: 54969 ENSG00000056050 UniProt: Q9NWY4 OMIM: 616614

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables chromatin binding activity; histone binding activity; and protein ADP-ribosyltransferase-substrate adaptor activity. Involved in DNA repair-dependent chromatin remodeling and double-strand break repair. Located in chromatin and nucleus. Is active in site of DNA damage. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

—

Mechanism