Alt. symbols: PMSL2 | H_DJ0042M02.9 | HNPCC4 | MLH4

Approved name: PMS1 homolog 2, mismatch repair system component
Alt. names: postmeiotic segregation increased (S. cerevisiae) 2, PMS2 postmeiotic segregation increased 2 (S. cerevisiae), PMS1 homolog 2, mismatch repair protein

Location: 7p22.1: 5970925 - 6009130 (-)
Gene type: protein_coding, 71 transcripts.

Scores: LoFtool: 0.382000 | pLI: 0.00000000 | LOEUF: 1.266

HGNC: 9122

NCBI: 5395, RefSeq: NG_008466.1

Ensembl: ENSG00000122512.17

LRG_161 | Status: public

OMIM: 600259

Expression | ProteinAtlas

The PMS2 encodes a mismatch repair endonuclease, which is an enzyme that plays an essential role in repairing DNA. This protein corrects DNA replication errors during cell division. The PMS2 protein dimerizes with the protein MLH1 to form a complex that coordinates the activities of other proteins that repair DNA replication errors. As an endonuclease, PMS2 introduces nicks into a discontinuous DNA strand, which allows for the replacement of the wrong DNA sequence. The PMS2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

Both monoallelic and biallelic mutations in PMS2 have been primarily associated with hereditary non-polyposis colorectal cancer type 4 [MIM:614337] and with mismatch repair cancer syndrome [MIM:276300], which is also known as Turcot syndrome and is characterized by the occurrence of a primary brain tumor and multiple colorectal polyps. Peron et al. (2008) also reported that PMS2 deficiency leads to a class switch recombination defect and causes hyper-IgM syndrome. The authors reported three pati ents with low number of B cells, reduced IgA and IgG, increased IgM levels, and abnormal antibody responses. The patients presented with recurrent infections, café-au-lait spots, lymphoma, colorectal carcinoma and brain tumors (PMID:18824584). In detail, various genetic alterations - deletions leading to frameshift and insert of a stop codon, intronic variants, missense mutations and truncating point mutations - have been detected in affected patients. Three missense mutations in PMS2 (P511K, T597S and M622I) have been functionally assessed and shown to affect the binding affinity of PMS2 towards MLH1 (PMID: 11793469). It is worth mentioning that detection of mutations in PMS2 is complicated by the occurrence of several PMS2 pseudogenes containing copies of exons of the PMS2 gene. Sequence exchange events between PMS2 and the pseudogenes result in allelic diversity and difficulties in mutation analysis. [Load More]