MSH6
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.
Overview
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.
CIViC 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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at MSH6 yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
External identifiers
Sources: HGNC HGNC:7329 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P52701 (protein name, function text, keywords and locations (REST API)); CIViC gene MSH6 (7 evidence items, 0 assertions, 7 variants; diseases: Colorectal Cancer, Endometrial Cancer, Transitional Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000116062 (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))
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).
- 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)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"MSH6" OR ABSTRACT:"MSH6" OR TITLE:"mutS homolog 6" OR ABSTRACT:"mutS homolog 6" OR TITLE:"DNA mismatch repair protein Msh6" OR ABSTRACT:"DNA mismatch repair protein Msh6" OR TITLE:"MSH-6" OR ABSTRACT:"MSH-6") 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 MSH6, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetMSH2
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Sarcomas (soft tissue, bone, GIST).
- TargetPMS2
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetMLH1
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TechnologyMSI and mismatch-repair testing
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Gastric & gastro-oesophageal junction cancer, Colorectal cancer.
- TermMicrosatellite-stable (MSS) / mismatch-repair proficient (pMMR)
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.
- BiomarkerdMMR (mismatch repair deficiency by IHC)
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.
- TermEndometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)
Shares VENTANA MMR RxDx Panel, Endometrial cancer.
- TermLynch syndrome
Shares VENTANA MMR RxDx Panel, Endometrial cancer, Colorectal cancer.