{"entity":{"id":"msh2","kind":"target","name":"MSH2","aka":["mutS homolog 2","DNA mismatch repair protein Msh2","HNPCC","HNPCC1","MSH-2","COCA1"],"tldr":"MSH2 (DNA mismatch repair protein Msh2) 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). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs.\n\nCIViC holds 8 clinical evidence items and 0 assertions across 8 variants, naming Nivolumab, 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 0.76, literature 0.98, genetic association 0.96, somatic mutation 0.97, animal model 0.65). In OnCo, 1 product record names it (VENTANA MMR RxDx Panel).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7325","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7325"},{"label":"UniProt P43246","url":"https://www.uniprot.org/uniprotkb/P43246/entry"},{"label":"NCBI Gene 4436","url":"https://www.ncbi.nlm.nih.gov/gene/4436"},{"label":"Ensembl ENSG00000095002","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000095002"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets"],"cancers":["colorectal","endometrial","ovarian","breast-cancer","gastric","skin-cancer","sarcoma","rectal-cancer","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["ventana-mmr-rxdx"],"companies":[],"institutions":[],"pathways":["colorectal-cancer-signalling","mismatch-repair-msi"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","paper-guedes-msh2-loss-primary-prostate-ccr-2017"],"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 3 therapies; CIViC holds 8 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.","Colorectal cancer: MSH2 loss is almost always inherited rather than sporadic, so an MSH2-deficient tumour points straight at Lynch syndrome. Where sequencing of MSH2 is clean, the cause may be a deletion of the 3' exons of the neighbouring EPCAM gene, whose read-through transcription methylates the MSH2 promoter in cis (Ligtenberg 2009)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MSH2","role":["drug-target","biomarker","dna-repair"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7325","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7325","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P43246","url":"https://www.uniprot.org/uniprotkb/P43246/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MSH2","url":"https://civicdb.org/features/3628","note":"8 evidence items, 0 assertions, 8 variants; diseases: Colorectal Cancer, Endometrial Cancer, Cancer, Transitional Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000095002","url":"https://platform.opentargets.org/target/ENSG00000095002/associations","note":"association with cancer (MONDO_0004992) 0.93; per-cancer scores at or above 0.5: colorectal cancer 0.92, gastric cancer 0.63, ovarian cancer 0.74, endometrial cancer 0.74, melanoma 0.52, sarcoma 0.53 (GraphQL API, CC0)"}],"specificity":"germline-variant","distribution":"many-types","specificityNote":"Germline variant: UniProt lists Lynch syndrome 1 (LYNCH1) 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 MSH2: RNA low tissue specificity; high antibody staining in 2 normal tissues; highest cancer staining glioma (4 of 12 high). Distribution: 7 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, Skin cancer (all types), Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 24 specific cancer types at or above 0.5 (Lynch syndrome, colorectal cancer, mismatch repair cancer syndrome, Muir-Torre syndrome, mismatch repair cancer syndrome 1, colon carcinoma and more). (Rule 2 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P43246","url":"https://www.uniprot.org/uniprotkb/P43246/entry","note":"involvement in disease"},{"label":"Human Protein Atlas MSH2 tissue","url":"https://www.proteinatlas.org/ENSG00000095002-MSH2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000095002 associations","url":"https://platform.opentargets.org/target/ENSG00000095002/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7325","ensembl":"ENSG00000095002","uniprot":"P43246","entrez":"4436","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Fishel et al, Cell, 1993, \"The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8252616/","biology":"Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognises single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognises larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. Location: Nucleus; Chromosome (UniProt). Locus 2p21-p16.3 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.92 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Endometrial cancer: Open Targets association 0.74 with endometrial cancer (MONDO_0011962); CIViC evidence names this disease","Ovarian cancer: Open Targets association 0.74 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 0.63 with gastric cancer (MONDO_0001056)","Skin cancer: Open Targets association 0.56 with skin cancer (MONDO_0002898)","Prostate cancer: msh2, msh6, mlh1 or pms2 inactivation, often by complex rearrangement 0.2-3% depending on disease state"],"targetClass":"other","prevalence":[{"cancerId":"prostate","pct":"0.2-3","measure":"MSH2, MSH6, MLH1 or PMS2 inactivation, often by complex rearrangement","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"cBioPortal mutation in prostate_msk_2024: MSH2 26 of 2,260 (1.2%), MSH6 27 (1.2%), PMS2 17 (0.8%), MLH1 16 (0.7%); deep deletion adds MSH2 21, MSH6 15. In prad_su2c_2019: MSH2 6 of 444, MSH6 6, MLH1 3. MSH2 protein loss on immunohistochemistry was present in 14 of 1,176 primary adenocarcinomas and small-cell carcinomas, 1.2% (Guedes 2017)."}]},"route":"/targets/msh2/","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":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"},{"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/"}],"pathway":[{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"}],"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-wardell-biliary-drivers-germline-j-hepatol-2018","kind":"paper","name":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","route":"/key-papers/paper-wardell-biliary-drivers-germline-j-hepatol-2018/"},{"id":"paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","kind":"paper","name":"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1","route":"/key-papers/paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009/"},{"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-guedes-msh2-loss-primary-prostate-ccr-2017","kind":"paper","name":"MSH2 loss in primary prostate cancer","route":"/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/"},{"id":"paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019","kind":"paper","name":"Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines","route":"/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/"},{"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/"}]}}