WRN Gene

HGNC Family	Exonucleases
Name	Werner syndrome, RecQ helicase-like
Description	This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe Werner syndrome protein (WRN) is a multifunctional RecQ helicase essential for preserving genomic integrity through roles in telomere maintenance, replication‐fork progression, and the prevention of premature cellular senescence. Loss of WRN function leads to accelerated telomere shortening, aberrant deletion of telomeres—particularly on the lagging strand—and other hallmarks of genomic instability that underlie premature aging phenotypes. WRN also contributes to proper nuclear organization and rRNA transcription, thereby influencing overall gene expression patterns and cell cycle kinetics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWRN is centrally positioned in multiple DNA repair pathways—including homologous recombination (HR), nonhomologous end joining (NHEJ), and base excision repair (BER)—by coordinating with a variety of repair factors. It interacts physically and functionally with proteins such as TRF2, POT1, Ku70/80, replication protein A, PARP-1, and RAD52 to enhance its helicase and exonuclease activities in processing complex DNA structures, facilitating long-range end resection, and resolving stalled replication forks. Furthermore, WRN’s activities are modulated by post-translational modifications (for example, acetylation by CBP/p300 and deacetylation by SIRT1) that regulate its subcellular localization and its engagement in the cellular response to genotoxic stress. These coordinated interactions not only safeguard genomic integrity but also shape cellular outcomes following DNA damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its classical roles in telomere and DNA repair pathways, WRN is integral to the resolution of secondary DNA structures such as G-quadruplexes and in the maintenance of fragile site stability during replication stress. Its ability to unwind G-rich and complex DNA substrates—as well as its functional interplay with nucleases like MUS81 and other RecQ helicases—explains its synthetic lethal interactions in certain cancers, particularly those exhibiting microsatellite instability. Collectively, these functions underscore WRN’s importance as both a guardian of genomic integrity and a potential therapeutic target in oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junko Oshima, Shurong Huang, Chong Pae, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw079"}], "href": "https://doi.org/10.1093/hmg/ddw079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26984941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26984941"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Junko Oshima, Julia M Sidorova, Raymond J Monnat "}, {"type": "b", "children": [{"type": "t", "text": "Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ageing Res Rev (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arr.2016.03.002"}], "href": "https://doi.org/10.1016/j.arr.2016.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26993153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26993153"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ramreddy Tippana, Helen Hwang, Patricia L Opresko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single-molecule imaging reveals a common mechanism shared by G-quadruplex-resolving helicases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1603724113"}], "href": "https://doi.org/10.1073/pnas.1603724113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27407146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27407146"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Raghavendra A Shamanna, Huiming Lu, Jessica K de Freitas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WRN regulates pathway choice between classical and alternative non-homologous end joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms13785"}], "href": "https://doi.org/10.1038/ncomms13785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27922005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27922005"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Niek van Wietmarschen, Sriram Sridharan, William J Nathan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Repeat expansions confer WRN dependence in microsatellite-unstable cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-020-2769-8"}], "href": "https://doi.org/10.1038/s41586-020-2769-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32999459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32999459"}]}]}]}
Synonyms	RECQ3
Proteins	WRN_HUMAN
NCBI Gene ID	7486
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

WRN has 9,678 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 140 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN 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 WRN gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of WRN 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 WRN gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with WRN gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with WRN 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 WRN gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of WRN 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 WRN gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with WRN gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with WRN gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of WRN gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing WRN 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 WRN gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing WRN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing WRN protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing WRN 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 WRN 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 WRN protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing WRN protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of WRN gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with WRN gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with WRN gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with WRN gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with WRN 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 WRN 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 WRN gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for WRN protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving WRN gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving WRN gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with WRN gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with WRN gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.