{"entity":{"id":"pms2","kind":"target","name":"PMS2","aka":["PMS1 homolog 2, mismatch repair system component","Mismatch repair endonuclease PMS2","H_DJ0042M02.9","HNPCC4","MLH4","PMS-2","PMSL2"],"tldr":"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.","summary":"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.\n\nCIViC 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).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9122","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9122"},{"label":"UniProt P54278","url":"https://www.uniprot.org/uniprotkb/P54278/entry"},{"label":"NCBI Gene 5395","url":"https://www.ncbi.nlm.nih.gov/gene/5395"},{"label":"Ensembl ENSG00000122512","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000122512"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","endometrial","ovarian","breast-cancer","gastric","hcc","non-hodgkin-lymphoma","skin-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["ventana-mmr-rxdx"],"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: 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PMS2","role":["drug-target","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:9122","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9122","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P54278","url":"https://www.uniprot.org/uniprotkb/P54278/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PMS2","url":"https://civicdb.org/features/4371","note":"3 evidence items, 0 assertions, 3 variants; diseases: Glioblastoma, Endometrial Cancer, Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000122512","url":"https://platform.opentargets.org/target/ENSG00000122512/associations","note":"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)"},{"label":"IntOGen PMS2","url":"https://www.intogen.org/search?gene=PMS2","note":"driver in 1 cohort (Act 0, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:9122","ensembl":"ENSG00000122512","uniprot":"P54278","entrez":"5395","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).","whereFound":["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)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/pms2/","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":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"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":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"ventana-mmr-rxdx","kind":"drug","name":"VENTANA MMR RxDx Panel","route":"/drugs/ventana-mmr-rxdx/"}]}}