# POLE

Source: https://onco.cc/targets/pole/  
OnCo record `pole` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: DNA polymerase epsilon, catalytic subunit; DNA polymerase epsilon catalytic subunit A; POLE1
- Tags: cancer-genes-wave
- Symbol: POLE
- Class: oncogene
- 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).
- Where found: 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%

## 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.

## Sources

- HGNC HGNC:9177: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9177
- UniProt Q07864: https://www.uniprot.org/uniprotkb/Q07864/entry
- NCBI Gene 5426: https://www.ncbi.nlm.nih.gov/gene/5426
- Ensembl ENSG00000177084: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177084

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Ovarian cancer](https://onco.cc/cancers/ovarian/)
- terms: [Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)](https://onco.cc/terms/mss-pmmr/), [POLE ultramutation (POLEmut)](https://onco.cc/terms/pole-ultramutation/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- trials: [RAINBO](https://onco.cc/trials/rainbo/)
- key papers: [Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas](https://onco.cc/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/), [Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer](https://onco.cc/key-papers/paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016/)

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JSON: https://onco.cc/api/v1/entities/pole.json