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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.
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).
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.
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.
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.
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.
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.)
Sources: UniProt P52701; Human Protein Atlas MSH6 tissue; Open Targets ENSG00000116062 associations
First described 1995. 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". Source.
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))
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Cerebellum, Heart muscle, Hippocampus, Liver, Parathyroid gland, Skeletal muscle, Small intestine, Smooth muscle.
RNA cancer enhanced: Testicular Germ Cell Tumor 118 pTPM.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.
Guidelines recommending universal mismatch repair testing in pancreatic cancer, by immunohistochemistry or sequencing rather than PCR alone, rest on this and similar series.
It matters for how the test is done. A mismatch repair assay designed around the colorectal mechanism, looking for MLH1 promoter methylation and simple mutations, can miss the prostate mechanism entirely, which is one reason microsatellite instability was under-recognised in this disease for so long.
It is the evidence behind universal mismatch repair testing of every colorectal cancer, which is now standard in most guidelines and which, as a by-product, identifies everyone eligible for immunotherapy.
Query 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.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer, Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer, Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer, Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, Identification of Lynch syndrome among patients with colorectal cancer.
Shares Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, VENTANA MMR RxDx Panel, Identification of Lynch syndrome among patients with colorectal cancer, Endometrial cancer.
Shares Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer, Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations, Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, Identification of Lynch syndrome among patients with colorectal cancer.