| MLH1 | |
|---|---|
| Full Name | MutL Homolog 1 |
| Symbol | MLH1 |
| Chromosomal Location | 3p22.2 |
| NCBI Gene ID | [4292](https://www.ncbi.nlm.nih.gov/gene/4292) |
| OMIM | [120436](https://www.omim.org/entry/120436) |
| Ensembl ID | [ENSG00000082142](https://ensembl.org/Homo_species/Gene/Summary?g=ENSG00000082142) |
| UniProt ID | [P40692](https://www.uniprot.org/uniprot/P40692) |
| Associated Diseases | [Lynch Syndrome](/diseases/lynch-syndrome), [Colorectal Cancer](/diseases/colorectal-cancer), [Amyotrophic Lateral Sclerosis](/diseases/als), [Parkinson's Disease](/diseases/parkinsons-disease) |
MLH1 (MutL Homolog 1) encodes a key DNA mismatch repair (MMR) protein that is essential for maintaining genomic stability. MLH1 forms a heterodimer with PMS2 (MutLα) and plays a central role in recognizing and repairing DNA mismatches, insertion/deletion loops, and coordinating the excision and resynthesis steps of MMR[1].
MLH1 functions as:
Beyond MMR, MLH1 participates in:
MLH1 is the most frequently mutated gene in Lynch syndrome, an autosomal dominant condition characterized by early-onset colorectal cancer, endometrial cancer, and other malignancies[2]. Over 300 pathogenic variants have been identified.
Reduced MLH1 expression has been observed in ALS motor neurons, contributing to increased DNA damage accumulation and accelerated disease progression[3].
MLH1 variants may modify PD risk through impaired mitochondrial DNA repair. Studies show decreased MLH1 levels in PD substantia nigra neurons[4].
| Brain Region | Expression Level |
|---|---|
| Cerebral Cortex | High |
| Hippocampus | High |
| Spinal Cord | High (motor neurons) |
| Substantia Nigra | Moderate-High |
| Cerebellum | Moderate |
| Variant | Type | Function | Associated Phenotype |
|---|---|---|---|
| p.K14A | Missense | Neutral | Common polymorphism |
| p.I219V | Missense | Partial loss | Risk modifier |
| p.G674E | Missense | Severe loss | Lynch syndrome |