{"entity":{"id":"msh6","kind":"target","name":"MSH6","aka":["mutS homolog 6","DNA mismatch repair protein Msh6","MSH-6"],"tldr":"MSH6 (DNA mismatch repair protein Msh6) is a gene. 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 MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognises single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA.\n\nCIViC holds 7 clinical evidence items and 0 assertions across 7 variants, naming Durvalumab and Anti-PD-1 Monoclonal Antibody MEDI0680. Open Targets scores its association with cancer at 0.93 (direct and indirect evidence; datatypes genetic literature 0.91, affected pathway 0.61, literature 0.97, genetic association 0.96, somatic mutation 0.96, animal model 0.42). In OnCo, 1 product record names it (VENTANA MMR RxDx Panel).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7329","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7329"},{"label":"UniProt P52701","url":"https://www.uniprot.org/uniprotkb/P52701/entry"},{"label":"NCBI Gene 2956","url":"https://www.ncbi.nlm.nih.gov/gene/2956"},{"label":"Ensembl ENSG00000116062","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000116062"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["colorectal","endometrial","ovarian","breast-cancer","gastric","prostate","skin-cancer","sarcoma"],"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 2 therapies; CIViC holds 7 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.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Transitional Cell Carcinoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MSH6","role":["drug-target","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7329","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7329","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P52701","url":"https://www.uniprot.org/uniprotkb/P52701/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MSH6","url":"https://civicdb.org/features/2478","note":"7 evidence items, 0 assertions, 7 variants; diseases: Colorectal Cancer, Endometrial Cancer, Transitional Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000116062","url":"https://platform.opentargets.org/target/ENSG00000116062/associations","note":"association with cancer (MONDO_0004992) 0.93; per-cancer scores at or above 0.5: colorectal cancer 0.92, gastric cancer 0.67, prostate cancer 0.60, ovarian cancer 0.76, endometrial cancer 0.87, sarcoma 0.52 (GraphQL API, CC0)"}],"specificity":"germline-variant","distribution":"many-types","specificityNote":"Germline variant: UniProt lists Lynch syndrome 5 (LYNCH5) 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 MSH6: RNA low tissue specificity; high antibody staining in 35 normal tissues; highest cancer staining breast cancer (11 of 11 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, Prostate cancer, Skin cancer (all types) and more); Open Targets associates it with 26 specific cancer types at or above 0.5 (Lynch syndrome, colorectal cancer, endometrial cancer, mismatch repair cancer syndrome, mismatch repair cancer syndrome 1, endometrial carcinoma and more). (Rule 2 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P52701","url":"https://www.uniprot.org/uniprotkb/P52701/entry","note":"involvement in disease"},{"label":"Human Protein Atlas MSH6 tissue","url":"https://www.proteinatlas.org/ENSG00000116062-MSH6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000116062 associations","url":"https://platform.opentargets.org/target/ENSG00000116062/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7329","ensembl":"ENSG00000116062","uniprot":"P52701","entrez":"2956","firstDescribed":1995,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Palombo et al, Science, 1995, \"GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7604265/","biology":"Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerises with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognises single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. Location: Nucleus; Chromosome (UniProt). Locus 2p16.3 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.92 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Endometrial cancer: Open Targets association 0.87 with endometrial cancer (MONDO_0011962); CIViC evidence names this disease","Ovarian cancer: Open Targets association 0.76 with ovarian cancer (MONDO_0008170)","Breast cancer: Open Targets association 0.67 with breast cancer (MONDO_0007254)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.67 with gastric cancer (MONDO_0001056)","Prostate cancer: Open Targets association 0.60 with prostate cancer (MONDO_0008315)"],"targetClass":"other","prevalence":[]},"route":"/targets/msh6/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"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":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"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/"}],"paper":[{"id":"paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","kind":"paper","name":"Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer","route":"/key-papers/paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014/"},{"id":"paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","kind":"paper","name":"Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations","route":"/key-papers/paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018/"},{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","route":"/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/"},{"id":"paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","kind":"paper","name":"Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade","route":"/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/"}]}}