mutS homolog 6
Annotations refreshed 1 month ago.
Diagnostic Grade (Green)
Additional findings health related
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdditional findings health related - adult specific
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdditional findings health related - CNV analysis adult specific
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdult solid tumours cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdult solid tumours for rare disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownBladder cancer pertinent cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedBrain cancer pertinent cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedChildhood solid tumours
BIALLELIC, autosomal or pseudoautosomal+31 more panels — install the extension to see the full list inline on any page.
Lynch syndrome
endometrial cancer
Constitutional mismatch repair deficiency syndrome
colorectal cancer
mismatch repair cancer syndrome 1
endometrial carcinoma
colon carcinoma
uterine corpus cancer
hereditary nonpolyposis colon cancer
ovarian cancer
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
DNA mismatch repair protein Msh6
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
Curated MONDO disease pages that list MSH6 among their top associated genes.
MSH6 · P52701
Mean pLDDT
77.1/ 100
Confident
1,360 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
