MLH1 Gene - Mismatch Repair Protein
Key player in DNA mismatch repair and hereditary cancer predisposition
Gene Information Card
| Symbol | MLH1 |
|---|---|
| Full Name | mutL homolog 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | 4292 ncbi.nlm.nih.gov/gene/4292 |
| Ensembl ID | ENSG00000076242 |
| UniProt ID | P40692 |
| OMIM ID | 120436 |
| HGNC ID | 7127 |
| Aliases | FCC2, hMLH1, COCA2 |
Description
The MLH1 gene encodes a protein critical for DNA mismatch repair (MMR). It forms a heterodimer with PMS2 to correct errors during DNA replication. Loss of function leads to microsatellite instability and increased mutation rates, predisposing to cancers, particularly Lynch syndrome (hereditary nonpolyposis colorectal cancer).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (hereditary nonpolyposis colorectal cancer) | Germline loss-of-function mutations in MLH1 impair MMR, causing microsatellite instability and tumorigenesis | ClinVar, OMIM |
| Muir-Torre syndrome | MLH1 mutations lead to defective MMR, associated with sebaceous neoplasms and visceral malignancies | ClinVar, OMIM |
| Colorectal cancer (sporadic) | Somatic MLH1 promoter hypermethylation silences expression, contributing to microsatellite instability | COSMIC, NCBI |
| Endometrial cancer | MLH1 loss via mutation or methylation drives microsatellite instability in endometrial tissue | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Colon | 15.2 | Medium |
| Small intestine | 14.8 | Medium |
| Ovary | 12.1 | Medium |
| Breast | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.3 | Cervical cancer cell line |
| HCT116 | 18.7 | Colorectal carcinoma; MLH1-deficient |
| MCF7 | 12.5 | Breast cancer cell line |
| A549 | 10.2 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.350C>T (p.Thr117Met) | Missense | Common in Lynch syndrome | Loss of MMR function |
| c.793C>T (p.Arg265Cys) | Missense | Rare | Impaired heterodimerization with PMS2 |
| c.1667+1G>A | Splice site | Found in Lynch syndrome families | Exon skipping, protein truncation |
| Promoter hypermethylation | Epigenetic | Frequent in sporadic colorectal cancer | Transcriptional silencing |
Mutation functional classification
Loss of Function (LOF)
Most MLH1 mutations are loss-of-function, disrupting MMR and leading to microsatellite instability.
Gain of Function (GOF)
Not reported for MLH1.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg265Cys) may exert dominant-negative effects by interfering with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • DNA mismatch repair (GO:0006298) | • ATP binding (GO:0005524) |
| • MutLalpha complex (GO:0032301) | • DNA repair (GO:0006281) |
| • Protein heterodimerization activity (GO:0046982) |
Pathways
• Mismatch repair (KEGG: hsa03430)
• Colorectal cancer (KEGG: hsa05210)
• MicroRNAs in cancer (KEGG: hsa05206)
Protein Summary
MLH1 is a 756-amino acid protein that functions as a central component of the mismatch repair system. It forms the MutLalpha heterodimer with PMS2, recognizing and repairing DNA replication errors. The protein has ATPase activity and interacts with other MMR proteins. Defects in MLH1 cause Lynch syndrome and are implicated in various sporadic cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MLH1 Knockout HEK293 Cell Line | EDC08266 | Human | 4292 | Details Get a Quote |
| MLH1 Knockout HeLa Cell Line | EDJ-KQ43083 | Human | 4292 | Details Get a Quote |
| MLH1 Knockout A-549 Cell Line | EDJ-KQ44299 | Human | 4292 | Details Get a Quote |
| MLH1 Knockout HCT 116 Cell Line | EDJ-KQ44300 | Human | 4292 | Details Get a Quote |
| MLH1 Knockout AGS Cell Line | EDJ-KZ352 | Human | 4292 | Details Get a Quote |
| MLH1 (p.S252*) Point Mutation in HAP1 Cell Line | EDC03544 | Human | 4292 | Details Get a Quote |
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