MSH3 encodes a protein that partners with MSH2 to form MutS beta, a key component of the DNA mismatch repair system that recognizes and corrects errors made during DNA replication. It acts as a tumor suppressor: loss of MSH3 function leads to mismatch repair deficiency, an elevated mutation rate, and increased cancer risk, and the gene is frequently altered in mismatch repair-deficient colorectal cancers. Defects in MSH3 are linked to susceptibility to endometrial cancer, and inherited mutations are associated with an autosomal recessive form of familial adenomatous polyposis, with minimal evidence for a role in Lynch syndrome. Tumors with mismatch repair deficiency, including those involving MSH3, tend to respond well to immune checkpoint inhibitor therapies.
MSH3 encodes the MSH2-partner protein MutS beta, whose loss impairs DNA mismatch repair and is associated with autosomal recessive familial adenomatous polyposis and mismatch-repair-deficient cancers.
PM2 supporting: gnomAD v4.1 shows an allele frequency of 4.46249e-05 with zero homozygotes. BP4 supporting: REVEL score 0.202 is below the generic BP4 threshold of 0.29.
Admixed American 4 / 59,980 |
0.0067% |
European (non-Finnish) 64 / 1,179,766 |
0.0054% |
East Asian 1 / 44,844 |
0.0022% |
South Asian 2 / 91,064 |
0.0022% |
African/African American 1 / 74,778 |
0.0013% |
Admixed American 3 / 34,590 |
0.0087% |
African/African American 1 / 16,244 |
0.0062% |
European (non-Finnish) 2 / 113,578 |
0.0018% |
