AlphaFold predicted structure
MLH1 · P40692
Mean pLDDT
77.3/ 100
Confident
756 residues
Confidence breakdown
- Very high(≥ 90)51%
- Confident(70–90)23%
- Low(50–70)6%
- Very low(< 50)20%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
MLH1
Chr 3p22.2mutL homolog 1
- Aliases:
- HNPCC, FCC2, HNPCC2, MLH-1
- MANE:
- ENST00000231790.8
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Additional findings health related
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdditional findings health related - adult specific
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdditional findings health related - CNV analysis adult specific
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdult solid tumours cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownAdult solid tumours for rare disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownBladder cancer pertinent cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedBrain cancer pertinent cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, NOT imprintedChildhood solid tumours
BIALLELIC, autosomal or pseudoautosomal
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Disease associations (Open Targets)
Lynch syndrome
0.85mismatch repair cancer syndrome 1
0.81colorectal cancer
0.79Muir-Torre syndrome
0.76colon carcinoma
0.74Constitutional mismatch repair deficiency syndrome
0.71malignant colon neoplasm
0.70hereditary nonpolyposis colon cancer
0.68colonic neoplasm
0.68endometrial carcinoma
0.64
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
DNA mismatch repair protein Mlh1
Heterodimerizes 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. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis
Diseases associated with MLH1
Curated MONDO disease pages that list MLH1 among their top associated genes.