HPF1
protein-codinghistone PARylation factor 1
Gene summary
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]
- C4orf27
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HPF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017867.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 1 | 1 | 2 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 3 | 1 | 0 | 4 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060337.2 | 8 | MANE Select | |
| Ensembl | ENSP00000406598.1 | 8 | MANE Select | |
| Ensembl | ENSP00000575138.1 | 7 | Standard | |
| Ensembl | ENSP00000575138.1 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hpf1 | Danio rerio | Structure: whole organism Quality: increased curvature abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cellular response to DNA damage stimulus
- regulation of protein ADP-ribosylation
- peptidyl-serine ADP-ribosylation
Molecular Function
- protein binding
- zinc ion binding
- histone binding
- poly-ADP-D-ribose binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393381
- Coding exons
- 8
- Length
- 28489
- Individuals with no LoFs
- 125472
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 273
- Defined
- 125746
- p
- 0.00109
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0576 | 166 | 168 | 0.988 | 0.00000777 | 2285 |
| Missense (PolyPhen) | 28 | 42.173 | 0.66393 | 593 | ||
| Synonymous | 0.535 | 54 | 59.2 | 0.912 | 0.00000290 | 605 |
| Loss of Function | 1.19 | 11 | 16.2 | 0.680 | 8.24e-7 | 227 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00099 | 0.00098 | rare |
| Latino/Admixed American | 0.00048 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00052 | 0.00051 | rare |
| European (Non-Finnish) | 0.0014 | 0.0014 | notable |
| South Asian | 0.0022 | 0.0021 | notable |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a cofactor for serine ADP-ribosylation by conferring serine specificity on PARP1 and PARP2: interacts with PARP1 and PARP1 and is able to change amino acid specificity toward serine (PubMed:28190768). Promotes histone serine ADP- ribosylation in response to DNA damage, limiting DNA damage- induced PARP1 hyper-automodification, and ensuring genome stability (PubMed:27067600, PubMed:28190768). {ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768}.;
Recessive Scores
- pRec
- 0.0814
Intolerance Scores
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.25
Essentials
- Essential (gene trap)
- N