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PMS2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PMS2 gene

The PMS2 gene plays an essential role in DNA repair, helping to correct errors that occur during the replication process.

Normal Function

The PMS2 gene provides instructions for making a protein that is part of the mismatch repair (MMR) system. The PMS2 protein joins with the MLH1 protein to form a complex that coordinates the removal and replacement of incorrect DNA sequences generated during cell division. The gene is located on chromosome 7, which also contains nonfunctional pseudogenes that can complicate genetic testing due to the exchange of genetic material.

Health Conditions Related to Genetic Changes

Constitutional mismatch repair deficiency syndrome

Constitutional mismatch repair deficiency (CMMRD) syndrome occurs when an individual inherits a pathogenic variant in both copies of the PMS2 gene. This leads to a total lack of functional PMS2 protein, causing DNA errors to accumulate in all cells. This significantly increases the risk of developing cancers—particularly leukemia, lymphoma, and colorectal cancer—in early childhood.

Lynch syndrome

Lynch syndrome occurs when an individual inherits one normal copy of the PMS2 gene and one copy with a pathogenic variant. While the normal copy usually provides enough functional protein to repair DNA, cancer risk increases if the remaining normal copy acquires a mutation during the person's lifetime. Individuals with PMS2-associated Lynch syndrome have a lower risk of colorectal cancer and tend to develop it later in life compared to those with other MMR gene variants.

Genomic Location

The PMS2 gene is found on chromosome 7.

Frequently Asked Questions

Yes, individuals with PMS2-associated Lynch syndrome generally have a lower lifetime risk of colorectal cancer and tend to develop it later than those with mutations in MLH1, MSH2, or MSH6. Consequently, clinical guidelines often recommend starting colorectal cancer screening later, typically around age 30 to 35, rather than the age 20 to 25 recommended for other Lynch syndrome variants. However, patients still require regular screening for other associated cancers, such as endometrial and ovarian cancer, and should discuss personalized surveillance plans with their healthcare provider.
Having one mutated copy typically results in Lynch syndrome, where the remaining healthy gene usually provides enough protein to maintain normal DNA repair. In this scenario, cancer risk is elevated but generally lower than in other Lynch syndrome types, and colorectal cancer tends to develop later in life, often in the 40s or 50s. In contrast, inheriting two mutated copies causes Constitutional Mismatch Repair Deficiency (CMMRD) syndrome. This condition leads to a total lack of functional repair protein in all cells, resulting in a significantly higher risk of developing multiple cancers, including leukemia, lymphoma, and colorectal cancer, usually in early childhood.
The PMS2 gene is located on chromosome 7, which also contains nonfunctional copies of the gene known as pseudogenes. These pseudogenes are very similar in sequence to the functional PMS2 gene, which can confuse standard genetic testing methods. If the laboratory equipment mistakenly reads the pseudogene sequence instead of the real gene, it may produce false-positive results or miss actual mutations. Therefore, specialized testing protocols are required to distinguish between the functional gene and the pseudogenes to ensure accurate diagnosis.
Children with CMMRD syndrome, caused by biallelic PMS2 mutations, face a high risk of developing hematologic malignancies such as leukemia and lymphoma, as well as solid tumors like colorectal cancer. These cancers typically present in early childhood, often before the age of 10. Because the DNA repair system is completely non-functional in all cells, the accumulation of genetic errors is rapid, making early and vigilant screening for both blood disorders and gastrointestinal cancers critical for these patients.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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