MutS homolog 6 (MSH6) is one of the mismatch repair proteins and is encoded by the MSH6 gene, which is located on chromosome 2 and is 23,806 bp in length, including 10 exons and 83 untranslated regions. MutS homolog 6 (MSH6) is the major mismatch contacting component of the MSH2-MSH6 heterodimeric complex (MutSalpha) that mediates DNA mismatch repair (MMR) of simple mispairs and small insertion-deletion loops in eukaryotes. The MSH6 protein consists of 1,358 amino acid residues and forms a heterodimer with another mismatch repair protein, MSH2. The MSH2-MSH6 heterodimeric complex can recognize base-base substitution and single-base insertion/deletion mismatches. Germline mutations of MSH6 lead to high susceptibility to glioma, as well as some benign or malignant tumors in other organs. The MSH6 gene is one of the mismatch repair genes involved in Lynch syndrome and its mutations account for 10-20% of Lynch syndrome.