# MLH1

Source: https://onco.cc/targets/mlh1/  
OnCo record `mlh1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MLH1 (DNA mismatch repair protein Mlh1) is a gene. The public catalogues list it as a drug target, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Ovarian cancer, Endometrial cancer and 4 more.

## Summary

Heterodimerises with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2.

CIViC holds 29 clinical evidence items and 0 assertions across 31 variants, naming Nivolumab and Oxaliplatin. Open Targets scores its association with cancer at 0.92 (direct and indirect evidence; datatypes genetic literature 0.92, affected pathway 0.61, literature 0.99, genetic association 0.94, somatic mutation 0.97, animal model 0.61). In OnCo, 1 product record names it (VENTANA MMR RxDx Panel).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: mutL homolog 1; DNA mismatch repair protein Mlh1; HNPCC; FCC2; HNPCC2; MLH-1; COCA2
- Tags: cancer-genes-wave
- Symbol: MLH1
- Class: other
- Biology: Heterodimerises with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Location: Nucleus; Chromosome (UniProt). Locus 3p22.2 (HGNC).
- Where found: Colorectal cancer: Open Targets association 0.91 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease; Ovarian cancer: Open Targets association 0.72 with ovarian cancer (MONDO_0008170); Endometrial cancer: Open Targets association 0.69 with endometrial cancer (MONDO_0011962); CIViC evidence names this disease; Breast cancer: Open Targets association 0.67 with breast cancer (MONDO_0007254); Gastric & gastro-oesophageal junction cancer: Open Targets association 0.63 with gastric cancer (MONDO_0001056); CIViC evidence names this disease; Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; CIViC holds 29 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Lynch Syndrome; Villous Adenoma.

## Sources

- HGNC HGNC:7127: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7127
- UniProt P40692: https://www.uniprot.org/uniprotkb/P40692/entry
- NCBI Gene 4292: https://www.ncbi.nlm.nih.gov/gene/4292
- Ensembl ENSG00000076242: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000076242

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [VENTANA MMR RxDx Panel](https://onco.cc/drugs/ventana-mmr-rxdx/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/)

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JSON: https://onco.cc/api/v1/entities/mlh1.json