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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.
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).
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.
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.
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerises with MLH1 to form MutL alpha.
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.
Germline variant: UniProt lists Lynch syndrome 4 (LYNCH4) under involvement in disease, and the record is a DNA repair gene; the medicines linked to it act through the loss (synthetic lethality) or use the variant to pick patients. HPA PMS2: RNA low tissue specificity; high antibody staining in 3 normal tissues; highest cancer staining glioma (3 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Endometrial cancer, Ovarian cancer, Breast cancer (all types), Gastric & gastro-oesophageal junction cancer, Hepatocellular carcinoma, Lymphoma and more); Open Targets associates it with 12 specific cancer types at or above 0.5 (Lynch syndrome, mismatch repair cancer syndrome, mismatch repair cancer syndrome 1, endometrial carcinoma, Non-polyposis Turcot syndrome, hereditary neoplastic syndrome and more). (Rule 2 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P54278; Human Protein Atlas PMS2 tissue; Open Targets ENSG00000122512 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Nicolaides N.C. et al, Nature, 1994, "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Breast, Bronchus, Caudate, Cervix, Colon, Duodenum.
Medium only: carcinoid, cervical cancer, colorectal cancer, endometrial cancer.
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.
It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.
Guidelines recommending universal mismatch repair testing in pancreatic cancer, by immunohistochemistry or sequencing rather than PCR alone, rest on this and similar series.
It is the evidence behind universal mismatch repair testing of every colorectal cancer, which is now standard in most guidelines and which, as a by-product, identifies everyone eligible for immunotherapy.
Query 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.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer, Endometrial cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, Identification of Lynch syndrome among patients with colorectal cancer, Endometrial cancer.
Shares VENTANA MMR RxDx Panel, Endometrial cancer.