POLE
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication.
- 3 · How drugs use it
No product in this corpus aims at POLE yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:9177 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q07864 (protein name, function text, keywords and locations (REST API)); CIViC gene POLE (14 evidence items, 0 assertions, 8 variants; diseases: Colorectal Cancer, Endometrial Cancer, Glioblastoma, Endometrial Adenocarcinoma, High Grade Glioma (GraphQL API, CC0)); Open Targets ENSG00000177084 (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)); IntOGen POLE (driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"POLE" OR ABSTRACT:"POLE" OR TITLE:"DNA polymerase epsilon, catalytic subunit" OR ABSTRACT:"DNA polymerase epsilon, catalytic subunit" OR TITLE:"DNA polymerase epsilon catalytic subunit A" OR ABSTRACT:"DNA polymerase epsilon catalytic subunit A" OR TITLE:"POLE1" OR ABSTRACT:"POLE1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about POLE, not a curated reading list.
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