MLH1
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.
Overview
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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Heterodimerises with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
- 3 · How drugs use it
No product in this corpus aims at MLH1 yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
External identifiers
Sources: HGNC HGNC:7127 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P40692 (protein name, function text, keywords and locations (REST API)); CIViC gene MLH1 (29 evidence items, 0 assertions, 31 variants; diseases: Colorectal Cancer, Endometrial Cancer, Stomach Carcinoma, Cancer, Lynch Syndrome and 1 more (GraphQL API, CC0)); Open Targets ENSG00000076242 (association with cancer (MONDO_0004992) 0.92; per-cancer scores at or above 0.5: colorectal cancer 0.91, gastric cancer 0.63, ovarian cancer 0.72, endometrial cancer 0.69, skin cancer 0.55, breast cancer 0.67 (GraphQL API, CC0))
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)
Notes
top- 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.
Latest papers
topQuery 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.
Similar pages
not linked directly; found by shared links- TargetMSH2
Shares VENTANA MMR RxDx Panel, Colorectal cancer (KEGG map), Skin cancer (all types), Endometrial cancer.
- TargetMSH6
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetPMS2
Shares VENTANA MMR RxDx Panel, Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetMUTYH
Shares Lung cancer (all types), Skin cancer (all types), Endometrial cancer, Breast cancer (all types).
- TargetBARD1
Shares Lung cancer (all types), Skin cancer (all types), Breast cancer (all types), CIViC.
- TargetPPP2R1A
Shares Lung cancer (all types), Skin cancer (all types), Endometrial cancer, CIViC.
- TargetRICTOR
Shares Lung cancer (all types), Skin cancer (all types), Breast cancer (all types), CIViC.
- TargetMECOM
Shares Lung cancer (all types), Skin cancer (all types), Endometrial cancer, Breast cancer (all types).