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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.
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.
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.
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.
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.
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).
Germline variant: UniProt lists Colorectal cancer 10 (CRCS10) under involvement in disease, and the record is a tumour suppressor; the medicines linked to it act through the loss (synthetic lethality) or use the variant to pick patients. HPA POLD1: RNA low tissue specificity; high antibody staining in 24 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Lung cancer (all types), Breast cancer (all types), Leukaemia, Lymphoma, Ovarian cancer, Myeloid neoplasms and more); Open Targets associates it with 13 specific cancer types at or above 0.5 (non-small cell lung carcinoma, acute lymphoblastic leukemia, colorectal cancer, acute myeloid leukemia, B-cell chronic lymphocytic leukemia, colorectal cancer, susceptibility to, 10 and more). (Rule 2 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P28340; Human Protein Atlas POLD1 tissue; Open Targets ENSG00000062822 associations
First described 1991. Earliest sequence paper UniProt cites for the protein: Chung D.W. et al, Proc. Natl. Acad. Sci. U.S.A, 1991, "Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene". Source.
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)
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).
RNA: low tissue specificity, detected in many normal tissues.
Medium: Adrenal gland, Bone marrow, Breast, Bronchus, Caudate, Cerebral cortex, Endometrium, Epididymis.
HPA POLD1 tissue · HPA POLD1 pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 0.03% | Exonuclease domain hotspot mutation; germline p.Ser478Asn | cBioPortal, exonuclease hotspots: 2 of 7,237 in crc_msk_2026 and 1 of 619 in coadread_dfci_2016; any POLD1 mutation reads 366 of 7,237, 5.1%, in crc_msk_2026, almost all passengers in hypermutated tumours. Germline POLD1 p.Ser478Asn and POLE p.Leu424Val were identified as high-penetrance predisposition variants in families with multiple adenomas and early-onset colorectal cancer, with POLD1 also predisposing to endometrial cancer (Palles 2013). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query 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.
Shares Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas, POLE ultramutation (POLEmut), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types).
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, Ovarian cancer.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, IntOGen.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), IntOGen, Lung cancer (all types).
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, Ovarian cancer.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, IntOGen.
Shares Leukaemia (all types), CIViC, IntOGen, Lung cancer (all types).
Shares Leukaemia (all types), IntOGen, Ovarian cancer, Lung cancer (all types).