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. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
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).
- 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)
External identifiers
Built from HGNC, Ensembl, UniProt and ChEMBL idsProducts by modality and phase
Browse products →No product in the corpus is aimed at this target yet.
Trials
Evidence ranking →No trial in the corpus names this target or one of its products.
Resistance routes
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways
Pathway-to-drug matrix →No pathway diagram carries this target as a node.
Companion diagnostics
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Literature
Preprints →Query for this target: (TITLE:"MLH1" OR ABSTRACT:"MLH1" OR TITLE:"mutL homolog 1" OR ABSTRACT:"mutL homolog 1" OR TITLE:"DNA mismatch repair protein Mlh1" OR ABSTRACT:"DNA mismatch repair protein Mlh1" OR TITLE:"HNPCC" OR ABSTRACT:"HNPCC" OR TITLE:"FCC2" OR ABSTRACT:"FCC2" OR TITLE:"HNPCC2" OR ABSTRACT:"HNPCC2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MLH1, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/mlh1.json. Licence CC BY-NC 4.0.