Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes 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 recognizes 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.
This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction
Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH6 (MutS alpha) (PubMed:7604264, PubMed:8942985). Forms a ternary complex with MutL alpha (MLH1-PMS1).
Interacts with MCM9 (PubMed:26300262). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165)
(Microbial infection) Interacts with herpes simplex virus 1 protein UL12
The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3)
A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world.
Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon.
Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.
A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer.
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to MSH6, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 1
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06708429 | Lynch Syndrome, Lynch Syndrome I, Lynch Syndrome II, Lynch Syndrome I (Site-specific Colonic Cancer), HNPCC, HNPCC Gene Mutation, Hereditary Cancer Syndrome, Hereditary Cancer, MLH1 Gene Mutation, MLH1 Gene Deletion+Duplication, MLH1 Loss of Expression, MLH1 Gene Inactivation, MSH2 Gene Mutation, MSH2 Gene Deletion+Duplication, MSH2 Loss of Expression, MSH2 Gene Inactivation, MSH6 Gene Mutation, MSH6 Loss of Expression, MSH6 Gene Inactivation, PMS2 Gene Mutation, PMS2 Gene Inactivation, PMS2 Loss of Expression | Lynch Syndrome X-Talk of Enteral Mucosa With Immune System | N/A | RECRUITING |
| NCT02760849 | Deleterious BARD1 Gene Mutation, Deleterious BRCA1 Gene Mutation, Deleterious BRCA2 Gene Mutation, Deleterious BRIP1 Gene Mutation, Deleterious EPCAM Gene Mutation, Deleterious MLH1 Gene Mutation, Deleterious MSH2 Gene Mutation, Deleterious MSH6 Gene Mutation, Deleterious PALB2 Gene Mutation, Deleterious PMS2 Gene Mutation, Deleterious RAD51C Gene Mutation, Deleterious RAD51D Gene Mutation, Hereditary Breast and Ovarian Cancer Syndrome, Premenopausal | Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations | NA | ACTIVE_NOT_RECRUITING |
| NCT02993068 | BARD1 Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, Estrogen Receptor Negative, HER2/Neu Negative, MLH1 Gene Mutation, MSH2 Gene Mutation, MSH6 Gene Mutation, PALB2 Gene Mutation, PMS2 Gene Mutation, Progesterone Receptor Negative, RAD51C Gene Mutation, RAD51D Gene Mutation, Triple-Negative Breast Carcinoma | Stand up to Cancer: MAGENTA (Making Genetic Testing Accessible) | NA | SUSPENDED |
| NCT01876511 | MSI Positive Colorectal Cancer, MSI Negative Colorectal Cancer, MSI Positive Non-Colorectal Cancers | Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C) | PHASE2 | COMPLETED |
| NCT05420064 | BRCA1 Mutation, POLD1 Gene Mutation, CDKN2A Mutation, BRCA2 Mutation, POLE Gene Mutation, APC Gene Mutation, ATM Gene Mutation, MLH1 Gene Mutation, BARD1 Gene Mutation, MSH2 Gene Mutation, BRIP1 Gene Mutation, MSH6 Gene Mutation, CHEK2 Gene Mutation, PMS2 Gene Mutation, PALB2 Gene Mutation, EPCAM Gene Mutation, RAD51C Gene Mutation, BMPR1A Gene Mutation, RAD51D Gene Mutation, SMAD4, PTEN Gene Mutation, GREM1 | An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results | NA | RECRUITING |
| NCT00261456 | Prostate Cancer, BRCA Mutation, Mismatch Repair Gene Mutation, Genetic Predisposition to Disease | The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer | N/A | ACTIVE_NOT_RECRUITING |
| NCT07472686 | MMR Mutation, Small Bowel Adenoma, Small-bowel Adenocarcinoma, Lynch Syndrome, Cancer | Small Bowel Capsule Endoscopy in Lynch Syndrome | N/A | RECRUITING |
| NCT04379999 | Lynch Syndrome | Atorvastatin ± Aspirin in Lynch Syndrome Syndrome | EARLY_PHASE1 | COMPLETED |
| NCT07450612 | Colorectal Cancer, Adenoma Colon, Adenoma Colon Polyp, Colon Adenoma, Colo-rectal Cancer, Colon Disease, Colon Neoplasm, Lynch Syndrome, Lynch Syndrome I, Lynch Syndrome II, Lynch Syndrome I (Site-specific Colonic Cancer), LYN Gene Mutation, Mismatch Repair Deficiency, Mismatch Repair Gene Mutation, MLH1 Gene Mutation, MSH2 Gene Mutation, MSH6 Gene Mutation, PMS2 Gene Mutation, EPCAM Gene Mutation | Liquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection | N/A | RECRUITING |
| NCT05704010 | Lynch Syndrome, Lynch Syndrome I, Lynch Syndrome II, MLH1 Gene Mutation, MSH2 Gene Mutation, MSH6 Gene Mutation, PMS2 Gene Mutation, Small Bowel Adenocarcinoma | Videocapsule Endoscopy in Lynch Syndrome | NA | RECRUITING |