POLD1
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.
Overview
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.
CIViC 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at POLD1 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:9175 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P28340 (protein name, function text, keywords and locations (REST API)); CIViC gene POLD1 (7 evidence items, 0 assertions, 4 variants; diseases: Colorectal Cancer, Lung Adenocarcinoma, Pancreatic Cancer, Lung Non-small Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000062822 (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)); IntOGen POLD1 (driver in 2 cohorts (Act 0, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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)
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 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.
Latest papers
topQuery for this target: (TITLE:"POLD1" OR ABSTRACT:"POLD1" OR TITLE:"DNA polymerase delta 1, catalytic subunit" OR ABSTRACT:"DNA polymerase delta 1, catalytic subunit" OR TITLE:"DNA polymerase delta catalytic subunit" OR ABSTRACT:"DNA polymerase delta catalytic subunit" OR TITLE:"CDC2" OR ABSTRACT:"CDC2") 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 POLD1, not a curated reading list.
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