Gene PMS2
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Also known as
HNPCC4, PMSL2, Mismatch Repair Protein 2Overview
PMS2 (PMS1 Homolog 2, Mismatch Repair System Component) encodes a key protein in the DNA mismatch repair (MMR) system, which corrects errors that occur during DNA replication. The PMS2 protein forms a heterodimer with MLH1, and this complex (MutL alpha) plays a critical role in identifying and repairing mismatched nucleotides and small insertion-deletion loops in newly synthesized DNA. Proper functioning of the mismatch repair system is essential for maintaining genomic stability and preventing the accumulation of mutations that could lead to cancer.Germline mutations in PMS2 cause Lynch syndrome, an autosomal dominant hereditary cancer predisposition syndrome. However, PMS2-associated Lynch syndrome tends to have a lower cancer risk and later age of onset compared to mutations in other MMR genes like MLH1 and MSH2. Individuals with PMS2 mutations have an increased risk of colorectal cancer, endometrial cancer, and other malignancies. Biallelic mutations in PMS2 can cause constitutional mismatch repair deficiency (CMMRD), a rare and severe childhood cancer predisposition syndrome. Genetic testing and counseling are important for families with PMS2 mutations to guide cancer surveillance and prevention strategies.