PMS2
PMS2 (Mismatch repair endonuclease PMS2) is an enzyme. The public catalogues list it as a drug target, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Endometrial cancer, Ovarian cancer and 5 more.
Overview
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerises with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
CIViC holds 3 clinical evidence items and 0 assertions across 3 variants, naming Nivolumab. Open Targets scores its association with cancer at 0.89 (direct and indirect evidence; datatypes genetic literature 0.86, affected pathway 0.61, literature 0.96, genetic association 0.94, somatic mutation 0.90). IntOGen calls it a driver in 1 cohort (0 activating, 0 loss-of-function), covering Hepatocellular Carcinoma. In OnCo, 1 product record names it (VENTANA MMR RxDx Panel).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PMS2 (Mismatch repair endonuclease PMS2) is an enzyme. The public catalogues list it as a drug target, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Endometrial cancer, Ovarian cancer and 5 more.
- 1 · What it is
PMS2 (Mismatch repair endonuclease PMS2) is an enzyme. The public catalogues list it as a drug target, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Endometrial cancer, Ovarian cancer and 5 more.
- 2 · What goes wrong in cancer
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerises with MLH1 to form MutL alpha.
- 3 · How drugs use it
No product in this corpus aims at PMS2 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Sources: HGNC HGNC:9122 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P54278 (protein name, function text, keywords and locations (REST API)); CIViC gene PMS2 (3 evidence items, 0 assertions, 3 variants; diseases: Glioblastoma, Endometrial Cancer, Cancer (GraphQL API, CC0)); Open Targets ENSG00000122512 (association with cancer (MONDO_0004992) 0.89; per-cancer scores at or above 0.5: colorectal cancer 0.88, gastric cancer 0.62, ovarian cancer 0.66, endometrial cancer 0.67, melanoma 0.52, sarcoma 0.51 (GraphQL API, CC0)); IntOGen PMS2 (driver in 1 cohort (Act 0, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerises with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. Location: Nucleus (UniProt). Locus 7p22.1 (HGNC).
- Colorectal cancer: Open Targets association 0.88 with colorectal cancer (MONDO_0005575)
- Endometrial cancer: Open Targets association 0.67 with endometrial cancer (MONDO_0011962); CIViC evidence names this disease
- Ovarian cancer: Open Targets association 0.66 with ovarian cancer (MONDO_0008170)
- Breast cancer: Open Targets association 0.66 with breast cancer (MONDO_0007254)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.62 with gastric cancer (MONDO_0001056)
- Hepatocellular carcinoma: IntOGen driver in 1 cohort (HCC)
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: CIViC lists 1 therapies; CIViC holds 3 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"PMS2" OR ABSTRACT:"PMS2" OR TITLE:"PMS1 homolog 2, mismatch repair system component" OR ABSTRACT:"PMS1 homolog 2, mismatch repair system component" OR TITLE:"Mismatch repair endonuclease PMS2" OR ABSTRACT:"Mismatch repair endonuclease PMS2" OR TITLE:"H_DJ0042M02.9" OR ABSTRACT:"H_DJ0042M02.9" OR TITLE:"HNPCC4" OR ABSTRACT:"HNPCC4" OR TITLE:"MLH4" OR ABSTRACT:"MLH4") 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 PMS2, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetMSH6
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetMSH2
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetMLH1
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TechnologyMSI and mismatch-repair testing
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Gastric & gastro-oesophageal junction cancer, Colorectal cancer.
- TermMicrosatellite-stable (MSS) / mismatch-repair proficient (pMMR)
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.
- BiomarkerdMMR (mismatch repair deficiency by IHC)
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.
- TermEndometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
Shares VENTANA MMR RxDx Panel, Endometrial cancer.
- TermLynch syndrome
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.