HPF1 Gene

Name histone PARylation factor 1
Description 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, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histone PARylation factor 1 (HPF1) is an essential regulator of the cellular response to DNA damage that functions by switching the activity of PARP1 (and PARP2) toward serine-specific ADP‑ribosylation. Studies have shown that, in the absence of HPF1, serine ADP‑ribosylation on substrates—including histones and PARP1 itself—is completely lost, indicating that HPF1 is both necessary and sufficient to instill this modification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, HPF1 forms a robust complex with PARP1 that not only promotes the ADP‑ribosylation of histones in trans but also limits the hyper‑automodification of PARP1, thereby fine‑tuning the DNA damage signaling processes essential for genome stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " HPF1’s role extends to influencing the binding affinity of certain PARP inhibitors toward the PARP1–DNA complex, suggesting its importance in modulating therapeutic responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, the observation that HPF1 is required for the transfer of ADP‑ribose onto the hydroxyl group of serine residues on both histone proteins and PARP1 itself underscores its central role at the crossroads of histone modification and PARP1 automodification in the maintenance of genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Juan José Bonfiglio, Pietro Fontana, Qi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine ADP-Ribosylation Depends on HPF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2017.01.003"}], "href": "https://doi.org/10.1016/j.molcel.2017.01.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28190768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28190768"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ian Gibbs-Seymour, Pietro Fontana, Johannes Gregor Matthias Rack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.03.008"}], "href": "https://doi.org/10.1016/j.molcel.2016.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27067600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27067600"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Pietro Fontana, Juan José Bonfiglio, Luca Palazzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine ADP-ribosylation reversal by the hydrolase ARH3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.28533"}], "href": "https://doi.org/10.7554/eLife.28533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28650317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28650317"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ivo A Hendriks, Sara C Buch-Larsen, Evgeniia Prokhorova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-26172-4"}], "href": "https://doi.org/10.1038/s41467-021-26172-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34625544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34625544"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhen Zhang, Hongwei Sun, Yu Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of hpf1 expression and function in early embryonic development of zebrafish."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Genes Evol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00427-018-0608-9"}], "href": "https://doi.org/10.1007/s00427-018-0608-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29549427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29549427"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Johannes Rudolph, Genevieve Roberts, Karolin Luger "}, {"type": "b", "children": [{"type": "t", "text": "Histone Parylation factor 1 contributes to the inhibition of PARP1 by cancer drugs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-20998-8"}], "href": "https://doi.org/10.1038/s41467-021-20998-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33531508"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33531508"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anthony K L Leung "}, {"type": "b", "children": [{"type": "t", "text": "SERious Surprises for ADP-Ribosylation Specificity: HPF1 Switches PARP1 Specificity to Ser Residues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2017.02.012"}], "href": "https://doi.org/10.1016/j.molcel.2017.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28257697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28257697"}]}]}]}
NCBI Gene ID 54969
API
Download Associations
Predicted Functions View HPF1's ARCHS4 Predicted Functions.
Co-expressed Genes View HPF1's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View HPF1's ARCHS4 Predicted Functions.

Functional Associations

HPF1 has 1,296 functional associations with biological entities spanning 5 categories (disease, phenotype or trait, functional term, phrase or reference, chemical, cell line, cell type or tissue, gene, protein or microRNA) extracted from 21 datasets.

Click the + buttons to view associations for HPF1 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of HPF1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
CCLE Cell Line Proteomics Cell lines associated with HPF1 protein from the CCLE Cell Line Proteomics dataset.
CellMarker Gene-Cell Type Associations cell types associated with HPF1 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of HPF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of HPF1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by HPF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with HPF1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with HPF1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GO Biological Process Annotations 2023 biological processes involving HPF1 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Cellular Component Annotations 2023 cellular components containing HPF1 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by HPF1 gene from the curated GO Molecular Function Annotations 2023 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of HPF1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of HPF1 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by HPF1 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of HPF1 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of HPF1 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by HPF1 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of HPF1 gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of HPF1 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of HPF1 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sanger Dependency Map Cancer Cell Line Proteomics cell lines associated with HPF1 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset.