NCIt definition : Human MSH3 wild-type allele is located within 5q11-q12 and is approximately 222 kb
in length. This allele, which encodes DNA mismatch repair protein Msh3, is involved
in DNA mismatch repair.;
NCIt note : The MLH3 gene is ubiquitously expressed in various tissues and two isoforms are produced
by alternative splicing. MLH3 interacts with MLH1 and shares the same interacting
region on MLH1 with PMS1 and PMS2. The balance of these three competing MLH1 partners
may be important in the repair of mismatches in DNA. Malfunction of the mismatch repair
system results in a mutator phenotype, which is manifested as microsatellite instability
(MSI). MSI is often divided into 2 forms: MSI-high (MSI-H) and MSI-low (MSI-L), based
quantitatively on the observed frequency of genomic mutations. An appreciable frequency
of somatic MLH3 mutations in MSI-H tumors is consistent with a possible role for this
gene in the progression of colorectal cancer tumorigenesis. Germline mutations of
this gene may also play a role in hereditary nonpolyposis colorectal cancer.;