{"entity":{"id":"pold1","kind":"target","name":"POLD1","aka":["DNA polymerase delta 1, catalytic subunit","DNA polymerase delta catalytic subunit","CDC2"],"tldr":"POLD1 (DNA polymerase delta catalytic subunit) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Lung cancer, Breast cancer and 5 more.","summary":"As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity.\n\nCIViC holds 7 clinical evidence items and 0 assertions across 4 variants, naming Pembrolizumab, ATR Inhibitor and Chk1 Inhibitor. Open Targets scores its association with cancer at 0.88 (direct and indirect evidence; datatypes genetic literature 0.83, clinical 0.99, literature 0.97, genetic association 0.72, somatic mutation 0.86). IntOGen calls it a driver in 2 cohorts (0 activating, 2 loss-of-function), covering Invasive Breast Carcinoma, Oesophageal Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9175","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9175"},{"label":"UniProt P28340","url":"https://www.uniprot.org/uniprotkb/P28340/entry"},{"label":"NCBI Gene 5424","url":"https://www.ncbi.nlm.nih.gov/gene/5424"},{"label":"Ensembl ENSG00000062822","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000062822"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","lung-cancer","breast-cancer","leukaemia","non-hodgkin-lymphoma","ovarian","myeloproliferative-neoplasms","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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 a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 7 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"POLD1","role":["drug-target","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:9175","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9175","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P28340","url":"https://www.uniprot.org/uniprotkb/P28340/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene POLD1","url":"https://civicdb.org/features/4384","note":"7 evidence items, 0 assertions, 4 variants; diseases: Colorectal Cancer, Lung Adenocarcinoma, Pancreatic Cancer, Lung Non-small Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000062822","url":"https://platform.opentargets.org/target/ENSG00000062822/associations","note":"association with cancer (MONDO_0004992) 0.88; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.71, colorectal cancer 0.76, urinary bladder cancer 0.51, ovarian cancer 0.69, endometrial cancer 0.60, melanoma 0.57 (GraphQL API, CC0)"},{"label":"IntOGen POLD1","url":"https://www.intogen.org/search?gene=POLD1","note":"driver in 2 cohorts (Act 0, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:9175","ensembl":"ENSG00000062822","uniprot":"P28340","entrez":"5424","biology":"As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Location: Nucleus (UniProt). Locus 19q13.33 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.76 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Lung cancer: Open Targets association 0.73 with lung cancer (MONDO_0008903)","Breast cancer: Open Targets association 0.73 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)","Leukaemia: Open Targets association 0.71 with leukaemia (MONDO_0005059)","Non-Hodgkin lymphoma: Open Targets association 0.71 with non-Hodgkin lymphoma (MONDO_0018908)","Ovarian cancer: Open Targets association 0.69 with ovarian cancer (MONDO_0008170)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/pold1/","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":"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/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}]}}