WRNIP1 Gene

HGNC Family	ATPases
Name	Werner helicase interacting protein 1
Description	Werner's syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene. [provided by RefSeq, Jul 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWRNIP1 plays a multifaceted role in safeguarding DNA replication under stress. It is recruited to replication factories and stalled forks, where it collaborates with RAD51 to prevent excessive MRE11‐mediated degradation of single‐stranded DNA, thereby preserving fork integrity (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]). In addition, WRNIP1 interacts with DNA polymerase δ, enhancing its initiation frequency and processivity during DNA synthesis, and it negatively regulates PrimPol levels via the proteasome, thus tuning fork restart mechanisms (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]). Genetic studies further indicate that WRNIP1 functions upstream of specialized translesion synthesis polymerases such as Pol η, with its loss mitigating the sensitivity of Pol η-deficient cells; its distinct domains (including the UBZ and leucine zipper motifs) are critical for these activities (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAn integral structural characteristic of WRNIP1 is its ubiquitin-binding zinc finger (UBZ) domain. This domain mediates selective binding to polyubiquitin chains through a novel surface that distinguishes it from the UBZ domains of other proteins (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "]). The UBZ domain is essential not only for WRNIP1’s rapid recruitment to DNA damage sites (for example, upon laser-induced irradiation) but also for its role in interstrand crosslink repair by catalyzing the loading of FANCD2/FANCI complexes via the Fanconi anemia pathway (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "]). Moreover, through its ubiquitin-dependent interactions, WRNIP1 helps counteract transcription-associated R-loop accumulation, thereby reducing potentially deleterious collisions between the replication and transcription machineries (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in DNA replication and repair, WRNIP1 contributes to diverse cellular processes. It associates with the nuclear envelope and nuclear pore complex components—as evidenced by its dynamic interaction with the Nup107-160 subcomplex and defined nuclear localization signals—suggesting functions in nucleocytoplasmic trafficking (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "]). In the context of innate immunity, WRNIP1 (sometimes referred to as WHIP) participates in assembling a mitochondrial signalosome—via its ubiquitin-binding domain—to bridge RIG-I with MAVS and facilitate antiviral signaling (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "]). Moreover, post-transcriptional regulation by miR-22 has been shown to reduce WRNIP1 levels and enhance radiosensitivity in small-cell lung cancer cells (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "]), while WRNIP1 also collaborates with the PIF1 helicase to resolve G-quadruplex DNA structures, thereby promoting smooth replication through difficult genomic regions (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Toshiki Tsurimoto, Ayako Shinozaki, Masaki Yano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase delta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2443.2004.00812.x"}], "href": "https://doi.org/10.1111/j.1365-2443.2004.00812.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15670210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15670210"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nicola Crosetto, Marzena Bienko, Richard G Hibbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Wrnip1 is localized in replication factories in a ubiquitin-binding zinc finger-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M803219200"}], "href": "https://doi.org/10.1074/jbc.M803219200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18842586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18842586"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akari Yoshimura, Masayuki Seki, Makoto Kanamori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interaction between WRNIP1 and RAD18."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Genet Syst (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1266/ggs.84.171"}], "href": "https://doi.org/10.1266/ggs.84.171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19556710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19556710"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Akari Yoshimura, Yume Kobayashi, Shusuke Tada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WRNIP1 functions upstream of DNA polymerase η in the UV-induced DNA damage response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.08.043"}], "href": "https://doi.org/10.1016/j.bbrc.2014.08.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25139235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25139235"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "N Kanu, T Zhang, R A Burrell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAD18, WRNIP1 and ATMIN promote ATM signalling in response to replication stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2015.427"}], "href": "https://doi.org/10.1038/onc.2015.427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26549024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26549024"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Giuseppe Leuzzi, Veronica Marabitti, Pietro Pichierri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WRNIP1 protects stalled forks from degradation and promotes fork restart after replication stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201593265"}], "href": "https://doi.org/10.15252/embj.201593265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27242363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27242363"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Akari Yoshimura, Mizuho Oikawa, Hitomi Jinbo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WRNIP1 Controls the Amount of PrimPol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.b18-00955"}], "href": "https://doi.org/10.1248/bpb.b18-00955"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31061318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31061318"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Akari Yoshimura, Tatsuya Sakakihara, Takemi Enomoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Domain Mapping of Werner Interacting Protein 1 (WRNIP1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.b21-00718"}], "href": "https://doi.org/10.1248/bpb.b21-00718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35110507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35110507"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Veronica Marabitti, Pasquale Valenzisi, Giorgia Lillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23031547"}], "href": "https://doi.org/10.3390/ijms23031547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35163467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35163467"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rebecca A Bish, Michael P Myers "}, {"type": "b", "children": [{"type": "t", "text": "Werner helicase-interacting protein 1 binds polyubiquitin via its zinc finger domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M701042200"}], "href": "https://doi.org/10.1074/jbc.M701042200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17550899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17550899"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nobuhiro Suzuki, Ahmed Rohaim, Ryuichi Kato, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.12.080"}], "href": "https://doi.org/10.1016/j.bbrc.2011.12.080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22209848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22209848"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Anna Socha, Di Yang, Alicja Bulsiewicz, et al. 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Synonyms	WHIP, BA420G6.2
Proteins	WRIP1_HUMAN
NCBI Gene ID	56897
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WRNIP1 has 7,300 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for WRNIP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

WRNIP1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WRNIP1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of WRNIP1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of WRNIP1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of WRNIP1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of WRNIP1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of WRNIP1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of WRNIP1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WRNIP1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of WRNIP1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of WRNIP1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WRNIP1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of WRNIP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WRNIP1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WRNIP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WRNIP1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of WRNIP1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing WRNIP1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of WRNIP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WRNIP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WRNIP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing WRNIP1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing WRNIP1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with WRNIP1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with WRNIP1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WRNIP1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WRNIP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with WRNIP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with WRNIP1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of WRNIP1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by WRNIP1 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 WRNIP1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with WRNIP1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with WRNIP1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with WRNIP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at WRNIP1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of WRNIP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of WRNIP1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing WRNIP1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with WRNIP1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with WRNIP1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.