| MSH3 | |
|---|---|
| Full Name | MutS Homolog 3 |
| Symbol | MSH3 |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | [4437](https://www.ncbi.nlm.nih.gov/gene/4437) |
| OMIM | [604952](https://www.omim.org/entry/604952) |
| Ensembl ID | [ENSG00000110899](https://ensembl.org/Homo_species/Gene/Summary?g=ENSG00000110899) |
| UniProt ID | [P54205](https://www.uniprot.org/uniprot/P54205) |
| Associated Diseases | [Amyotrophic Lateral Sclerosis](/diseases/als), [Huntington's Disease](/diseases/huntingtons-disease), [Colorectal Cancer](/diseases/colorectal-cancer), [Ataxia-Telangiectasia](/diseases/ataxia-telangiectasia) |
MSH3 (MutS Homolog 3) encodes a key DNA mismatch repair (MMR) protein that forms the MutSβ heterodimer with MSH2. This complex recognizes and repairs small insertion/deletion loops (IDLs) that arise during DNA replication, maintaining genomic stability.
MSH3 participates in DNA mismatch repair by:
Beyond canonical MMR, MSH3 plays a critical role in protecting against CAG/CTG repeat expansions[1]. MSH3 deficiency leads to dramatically increased somatic repeat expansion in neurons, contributing to neurodegenerative diseases.
MSH3 is a major genetic risk factor for ALS. GWAS studies have identified MSH3 variants associated with increased ALS risk[2]. MSH3 deficiency leads to:
MSH3 modulates HD pathogenesis through its role in somatic CAG repeat expansion[3]. MSH3 knockout mice show dramatically accelerated polyglutamine expansion in striatal neurons.
As a MMR gene, MSH3 loss contributes to microsatellite instability (MSI) and colorectal carcinogenesis. MSH3-deficient tumors show high mutation burden.
| Brain Region | Expression Level |
|---|---|
| Motor Cortex | High |
| Spinal Cord | High (motor neurons) |
| Striatum | High |
| Cerebellum | Moderate |
| Hippocampus | Moderate |
| Variant | Type | Function | Associated Phenotype |
|---|---|---|---|
| p.R497H | Missense | Partial loss | ALS risk modifier |
| p.T707A | Missense | Neutral | Common polymorphism |
| c.2146-1G>A | Splicing | Loss | Colorectal cancer |