MSH6 encodes a G/T mismatch-binding protein encoded by a gene localized to within 1 megabase of the related hMSH2 gene on chromosome 2. Unlike other mismatch repair genes, the MSH6 deficient cells showed alterations primarily in mononucleotide tracts, indicating the role MSH6 plays in maintaining the integrity of the human genome. Cells deficient in MSH6, accrue mutations in tracts of repeated nucleotides. MSH6 defects seem to be less common than MLH1 and MSH2 defects. They have been mostly observed in atypical HNPCC families and are characterized by a weaker family history of tumor development, higher age at disease onset, and low degrees of microsatellite instability (MSI) that predominantly involving mononucleotide runs.