POLE Gene

HGNC Family	Polymerases, DNA-directed (POL)
Name	polymerase (DNA directed), epsilon, catalytic subunit
Description	This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDNA polymerase epsilon (POLE) is a critical replicative enzyme whose catalytic subunit is endowed with intrinsic 3′–5′ exonuclease proofreading activity, ensuring high fidelity of leading‐strand DNA synthesis. Germline and somatic mutations in the proofreading (exonuclease) domain of POLE compromise its error‐correcting capacity, thereby accelerating the accumulation of base substitutions without inducing the classical microsatellite instability phenotype. Such defects underpin the ultramutated genomic landscapes observed in a subset of colorectal and endometrial tumors and predispose carriers to familial cancer syndromes, including polymerase proofreading–associated polyposis (PPAP)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe loss of POLE’s proofreading function not only drives a hypermutator phenotype—with mutation burdens that sometimes exceed 100 mutations per megabase—but also appears to generate a unique spectrum of base substitution patterns that serve as a molecular fingerprint for defects in leading‐strand replication. Intriguingly, tumors harboring POLE exonuclease domain mutations are frequently microsatellite‐stable and, in endometrial cancers, are associated with favorable clinical outcomes, possibly linked to enhanced antitumor immune responses. Moreover, these mutations have been documented in diverse clinical contexts including glioblastomas, where high neoantigen loads may confer sensitivity to immune checkpoint blockade therapy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond sporadic cancers, germline POLE mutations have been identified in families with multiple colorectal adenomas and early‐onset cancers, expanding the phenotypic spectrum to include extra‐intestinal neoplasms. Even biallelic POLE alterations have been implicated in complex developmental phenotypes characterized by growth restriction, immunodeficiency, and other systemic abnormalities. These findings not only highlight the indispensable role of POLE in safeguarding genome stability during cell proliferation but also underscore its emerging significance as both a prognostic biomarker and a therapeutic target in precision oncology, with implications for patient management and immunotherapy strategies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Claire Palles, Jean-Baptiste Cazier, Kimberley M Howarth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2503"}], "href": "https://doi.org/10.1038/ng.2503"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23263490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23263490"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David N Church, Sarah E W Briggs, Claire Palles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA polymerase ε and δ exonuclease domain mutations in endometrial cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt131"}], "href": "https://doi.org/10.1093/hmg/ddt131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23528559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23528559"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sarah Briggs, Ian Tomlinson "}, {"type": "b", "children": [{"type": "t", "text": "Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.4185"}], "href": "https://doi.org/10.1002/path.4185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23447401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23447401"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Young-Hoon Kang, Wiebke Chemnitz Galal, Andrea Farina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Properties of the human Cdc45/Mcm2-7/GINS helicase complex and its action with DNA polymerase epsilon in rolling circle DNA synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1203734109"}], "href": "https://doi.org/10.1073/pnas.1203734109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22474384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22474384"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Inge C van Gool, Florine A Eggink, Luke Freeman-Mills, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-16-0575"}], "href": "https://doi.org/10.1158/2159-8290.CD-16-0575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27683556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27683556"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Enric Domingo, Luke Freeman-Mills, Emily Rayner, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2014.143"}], "href": "https://doi.org/10.1038/modpathol.2014.143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25394778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25394778"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Caroline C Billingsley, David E Cohn, David G Mutch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymerase ɛ (POLE) mutations in endometrial cancer: clinical outcomes and implications for Lynch syndrome testing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cncr.29046"}], "href": "https://doi.org/10.1002/cncr.29046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25224212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25224212"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Melissa K McConechy, Aline Talhouk, Samuel Leung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-15-2233"}], "href": "https://doi.org/10.1158/1078-0432.CCR-15-2233"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26763250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26763250"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Bo Meng, Lien N Hoang, John B McIntyre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygyno.2014.05.006"}], "href": "https://doi.org/10.1016/j.ygyno.2014.05.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24844595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24844595"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Laura Valle, Eva Hernández-Illán, Fernando Bellido, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New insights into POLE and POLD1 germline mutations in familial colorectal cancer and polyposis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu058"}], "href": "https://doi.org/10.1093/hmg/ddu058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24501277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24501277"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Isabel Spier, Stefanie Holzapfel, Janine Altmüller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.29396"}], "href": "https://doi.org/10.1002/ijc.29396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25529843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25529843"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Anne Ml Jansen, Tom van Wezel, Brendy Ewm van den Akker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined mismatch repair and POLE/POLD1 defects explain unresolved suspected Lynch syndrome cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2015.252"}], "href": "https://doi.org/10.1038/ejhg.2015.252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26648449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26648449"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Daniel P Kane, Polina V Shcherbakova "}, {"type": "b", "children": [{"type": "t", "text": "A common cancer-associated DNA polymerase ε mutation causes an exceptionally strong mutator phenotype, indicating fidelity defects distinct from loss of proofreading."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-13-2892"}], "href": "https://doi.org/10.1158/0008-5472.CAN-13-2892"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24525744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24525744"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Fadwa A Elsayed, C Marleen Kets, Dina Ruano, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.11862"}], "href": "https://doi.org/10.18632/oncotarget.11862"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27612425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27612425"}]}]}]}
Synonyms	POLE1, CRCS12, FILS
Proteins	DPOE1_HUMAN
NCBI Gene ID	5426
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

POLE has 8,756 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 129 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

POLE Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by POLE gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of POLE 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 POLE 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 POLE 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 POLE 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 POLE 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 POLE 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 POLE 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 POLE 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 POLE 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 POLE gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of POLE 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 POLE gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with POLE 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 POLE gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of POLE 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 POLE 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 POLE gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with POLE gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of POLE gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing POLE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing POLE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with POLE 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 POLE protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing POLE protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of POLE gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with POLE gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with POLE gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with POLE gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of POLE protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with POLE 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 POLE 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 POLE 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 POLE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with POLE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for POLE protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at POLE 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 POLE gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of POLE 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 POLE from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.