MLH1
Chr 3ARADmutL homolog 1
Also known as: COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1, MMRCS1, hMLH1
The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]
Primary Disease Associations & Inheritance
Clinical highlights
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MLH1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
RECRUITINGThe IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
ACTIVE NOT RECRUITINGSurgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
ACTIVE NOT RECRUITINGLynch Syndrome Integrative Epidemiology and Genetics
RECRUITINGHow Epigenetic Changes in hMLH1 Connect Lab Research With Diagnosis in Gastric Cancer
ACTIVE NOT RECRUITINGLiquid Biopsy and Machine Learning for Early Colorectal Cancer, Adenomas, Lynch Cancers, and Residual Disease Detection
RECRUITINGVideocapsule Endoscopy in Lynch Syndrome
RECRUITINGEC_ItaLynch: Mainstreaming the Diagnosis of Lynch Syndrome
NOT YET RECRUITINGCamrelizumab Plus Anlotinib in Patients With Recurrent Sporadic MMRd Endometrial Cancer
NOT YET RECRUITINGCascade Testing in Families With Newly Diagnosed Hereditary Breast and Ovarian Cancer Syndrome
ACTIVE NOT RECRUITINGPredictive Value of PREMM5, MMRpredict, and Universal Tumor Screening for Lynch Syndrome in Vietnam
NOT YET RECRUITINGRefining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular Classification
RECRUITINGExternal Resources
Links to major genomics databases and tools