# MSH2

Source: https://onco.cc/targets/msh2/  
OnCo record `msh2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: mutS homolog 2; DNA mismatch repair protein Msh2; HNPCC; HNPCC1; MSH-2; COCA1
- Tags: cancer-genes-wave
- Symbol: MSH2
- Class: other
- 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).
- Where found: 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

## 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).

## Sources

- HGNC HGNC:7325: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7325
- UniProt P43246: https://www.uniprot.org/uniprotkb/P43246/entry
- NCBI Gene 4436: https://www.ncbi.nlm.nih.gov/gene/4436
- Ensembl ENSG00000095002: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000095002

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [VENTANA MMR RxDx Panel](https://onco.cc/drugs/ventana-mmr-rxdx/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/)
- key papers: [Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer](https://onco.cc/key-papers/paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014/), [Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations](https://onco.cc/key-papers/paper-wardell-biliary-drivers-germline-j-hepatol-2018/), [Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1](https://onco.cc/key-papers/paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009/), [Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations](https://onco.cc/key-papers/paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018/), [Identification of Lynch syndrome among patients with colorectal cancer](https://onco.cc/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/), [MSH2 loss in primary prostate cancer](https://onco.cc/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/), [Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines](https://onco.cc/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/), [Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade](https://onco.cc/key-papers/paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019/)

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