{"entity":{"id":"pole","kind":"target","name":"POLE","aka":["DNA polymerase epsilon, catalytic subunit","DNA polymerase epsilon catalytic subunit A","POLE1"],"tldr":"POLE (DNA polymerase epsilon catalytic subunit A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Ovarian cancer, Lung cancer and 5 more.","summary":"Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork.\n\nCIViC holds 14 clinical evidence items and 0 assertions across 8 variants, naming Pembrolizumab. Open Targets scores its association with cancer at 0.88 (direct and indirect evidence; datatypes genetic literature 0.78, clinical 0.99, affected pathway 0.76, literature 0.98, genetic association 0.82, somatic mutation 0.80). IntOGen calls it a driver in 2 cohorts (2 activating, 0 loss-of-function), covering Adrenocortical Carcinoma, Bladder Urothelial Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9177","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9177"},{"label":"UniProt Q07864","url":"https://www.uniprot.org/uniprotkb/Q07864/entry"},{"label":"NCBI Gene 5426","url":"https://www.ncbi.nlm.nih.gov/gene/5426"},{"label":"Ensembl ENSG00000177084","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177084"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","ovarian","lung-cancer","breast-cancer","non-hodgkin-lymphoma","leukaemia","myeloproliferative-neoplasms","endometrial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pole-ultramutation","tmb","mss-pmmr"],"trials":["rainbo"],"people":[],"bottlenecks":[],"keyPapers":["paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.99; IntOGen calls it an activating (Act) driver in 2 cohorts; CIViC holds 14 clinical evidence items on its variants; UniProt keyword \"DNA repair\". Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Endometrial Adenocarcinoma; High Grade Glioma.","Colorectal cancer: exonuclease-domain hotspot mutations in 0.7 to 2% of tumours, 1.0% of 6,517 in the largest pooled series (Domingo 2016). These are the ultramutated cases, median 172 mutations per megabase against 5.7 in microsatellite-stable disease (cBioPortal crc_msk_2026), and they are microsatellite stable, so neither a mismatch repair immunohistochemistry panel nor an MSI assay finds them. They are mutually exclusive with mismatch repair deficiency, occur in younger patients, carry CD8 infiltration as high as MSI-high tumours and have an excellent prognosis (recurrence hazard ratio 0.34). Germline POLE p.Leu424Val is a high-penetrance polyposis and colorectal cancer predisposition variant (Palles 2013). Case series report checkpoint inhibitor responses, but there is no colorectal approval on a POLE result alone."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"POLE","role":["drug-target","oncogene-driver","biomarker","dna-repair"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:9177","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9177","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q07864","url":"https://www.uniprot.org/uniprotkb/Q07864/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene POLE","url":"https://civicdb.org/features/4386","note":"14 evidence items, 0 assertions, 8 variants; diseases: Colorectal Cancer, Endometrial Cancer, Glioblastoma, Endometrial Adenocarcinoma, High Grade Glioma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000177084","url":"https://platform.opentargets.org/target/ENSG00000177084/associations","note":"association with cancer (MONDO_0004992) 0.88; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.70, colorectal cancer 0.77, gastric cancer 0.53, urinary bladder cancer 0.52, ovarian cancer 0.75, endometrial cancer 0.62 (GraphQL API, CC0)"},{"label":"IntOGen POLE","url":"https://www.intogen.org/search?gene=POLE","note":"driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA POLE: RNA tissue enhanced (bone marrow 21 nTPM); no normal tissue stained high. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Ovarian cancer, Lung cancer (all types), Breast cancer (all types), Lymphoma, Leukaemia, Myeloid neoplasms and more); Open Targets associates it with 16 specific cancer types at or above 0.5 (colorectal cancer, susceptibility to, 12, non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, exocrine pancreatic carcinoma, acute lymphoblastic leukemia and more). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q07864","url":"https://www.uniprot.org/uniprotkb/Q07864/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene POLE","url":"https://civicdb.org/features/4386","note":"14 evidence items, 0 assertions, 8 variants; diseases: Colorectal Cancer, Endometrial Cancer, Glioblastoma, Endometrial Adenocarcinoma, High Grade Glioma (GraphQL API, CC0)"},{"label":"IntOGen POLE","url":"https://www.intogen.org/search?gene=POLE","note":"driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas POLE tissue","url":"https://www.proteinatlas.org/ENSG00000177084-POLE/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000177084 associations","url":"https://platform.opentargets.org/target/ENSG00000177084/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9177","ensembl":"ENSG00000177084","uniprot":"Q07864","entrez":"5426","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Kesti et al, J. Biol. Chem, 1993, \"Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8486689/","biology":"Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork. Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication. Involved in DNA synthesis during DNA repair. Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation. Location: Nucleus (UniProt). Locus 12q24.33 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.77 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Ovarian cancer: Open Targets association 0.75 with ovarian cancer (MONDO_0008170)","Lung cancer: Open Targets association 0.73 with lung cancer (MONDO_0008903)","Breast cancer: Open Targets association 0.71 with breast cancer (MONDO_0007254)","Non-Hodgkin lymphoma: Open Targets association 0.71 with non-Hodgkin lymphoma (MONDO_0018908)","Leukaemia: Open Targets association 0.71 with leukaemia (MONDO_0005059)","Colorectal cancer: exonuclease (proofreading) domain hotspot mutation, ultramutated tumours 0.7-2%"],"targetClass":"oncogene","prevalence":[{"cancerId":"colorectal","pct":"0.7-2","measure":"Exonuclease (proofreading) domain hotspot mutation, ultramutated tumours","source":"https://doi.org/10.1016/S2468-1253(16)30014-0","note":"Pathogenic somatic POLE mutations in 66 of 6,517 colorectal cancers, 1.0%, across nine trials and cohorts (Domingo 2016). cBioPortal, counting only exonuclease hotspots (P286R, V411L, S297F, S459F and their neighbours): 52 of 7,237, 0.7%, in crc_msk_2026; 8 of 1,134 in crc_msk_2017; 11 of 534, 2.1%, in coadread_tcga_pan_can_atlas_2018; 6 of 224 in coadread_tcga_pub; 5 of 619 in coadread_dfci_2016; 12 of 1,015 in crc_sysucc_2022. The studies' own molecular subtype attributes agree: POLE in 8 of 1,134 (crc_msk_2017) and 13 of 1,468 (crc_eo_2020)."}]},"route":"/targets/pole/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"}],"term":[{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"},{"id":"pole-ultramutation","kind":"term","name":"POLE ultramutation (POLEmut)","route":"/terms/pole-ultramutation/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"trial":[{"id":"rainbo","kind":"trial","name":"RAINBO","route":"/trials/rainbo/"}],"paper":[{"id":"paper-palles-germline-pole-pold1-proofreading-nat-genet-2013","kind":"paper","name":"Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas","route":"/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/"},{"id":"paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016","kind":"paper","name":"Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer","route":"/key-papers/paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016/"}]}}