{"entity":{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","aka":["MMR proteins","mismatch repair","MLH1","MSH2","MSH6","PMS2","Lynch syndrome genes"],"tldr":"The four mismatch repair proteins proofread newly copied DNA; when a tumour loses one of them its DNA fills with small errors, and that state (dMMR or MSI-high) is what lets immunotherapy work across many cancers.","summary":"MLH1, MSH2, MSH6 and PMS2 form the MutS and MutL complexes that recognise and excise base mismatches and slipped repeats after replication. Loss of any one, by germline mutation (Lynch syndrome), somatic mutation or MLH1 promoter methylation, produces mismatch repair deficiency, read directly by immunohistochemistry for the four proteins or indirectly as microsatellite instability by PCR or sequencing. The two readouts under this record carry the label thresholds for pembrolizumab, nivolumab, ipilimumab, dostarlimab and durvalumab and the companion diagnostics that report them.","asOf":"2026-09-23","wikipedia":"https://en.wikipedia.org/wiki/DNA_mismatch_repair","links":[{"label":"HGNC HGNC:7127","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7127"},{"label":"HGNC HGNC:7325","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7325"},{"label":"HGNC HGNC:7329","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7329"},{"label":"HGNC HGNC:9122","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9122"}],"tags":["biomarker-parent"],"related":["dmmr-ihc","msi-high"],"cancers":["colorectal","endometrial","endometrial-mmr-deficient","gastric-msi-high"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","dostarlimab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","mss-pmmr","mlh1-promoter-methylation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Per-gene identifiers from HGNC: MLH1 HGNC:7127, ENSG00000076242, UniProt P40692; MSH2 HGNC:7325, ENSG00000095002, UniProt P43246; MSH6 HGNC:7329, ENSG00000116062, UniProt P52701; PMS2 HGNC:9122, ENSG00000122512, UniProt P54278."],"symbol":"MLH1, MSH2, MSH6, PMS2","role":[],"sources":[],"biology":"Deficient repair raises the mutation rate a hundredfold and produces frameshift neoantigens in repeat-containing genes, which is the mechanistic basis for checkpoint inhibitor sensitivity.","whereFound":["Colorectal cancer (about 15 percent, most sporadic through MLH1 methylation)","Endometrial cancer (about 25 to 30 percent)","Gastric, small bowel, urothelial and other Lynch-spectrum tumours"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/mmr/","neighbours":{"biomarker":[{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"}],"drug":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","route":"/terms/mlh1-promoter-methylation/"}]}}