MSH3: A Key Component of DNA Mismatch Repair
Comprehensive genomic and clinical overview of the MSH3 gene
Gene Information Card
| Symbol | MSH3 |
|---|---|
| Full Name | mutS homolog 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q14.1 |
| NCBI Gene ID | 4437 ncbi.nlm.nih.gov/gene/4437 |
| Ensembl ID | ENSG00000113318 |
| UniProt ID | P20585 |
| OMIM ID | 600887 |
| HGNC ID | 7326 |
| Aliases | DUC1, DUP, MRP1 |
Description
MSH3 (mutS homolog 3) encodes a protein that forms a heterodimer with MSH2 to create the MutSβ complex, which recognizes and binds to insertion/deletion loops (IDLs) during DNA mismatch repair. This gene is essential for maintaining genomic stability and is implicated in hereditary cancer syndromes and somatic tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (hereditary non-polyposis colorectal cancer) | Germline mutations in MSH3 cause defective mismatch repair, leading to microsatellite instability and increased cancer risk. | ClinVar, OMIM |
| Colorectal cancer (sporadic) | Somatic MSH3 mutations or loss of heterozygosity contribute to microsatellite instability and tumor progression. | COSMIC, NCBI |
| Endometrial cancer | MSH3 deficiency via somatic mutation or hypermethylation is associated with microsatellite instability. | ClinVar, COSMIC |
| Gastric cancer | MSH3 alterations are recurrent in microsatellite-unstable gastric tumors. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | Medium |
| Colon | 15.2 | Medium |
| Small intestine | 14.8 | Medium |
| Bone marrow | 12.1 | Medium |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.4 | Cervical cancer cell line |
| HCT116 | 14.2 | Colorectal carcinoma |
| MCF7 | 11.8 | Breast cancer |
| A549 | 10.5 | Lung carcinoma |
| K562 | 9.3 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1147C>T (p.Arg383*) | Nonsense | 0.02% in general population | Loss of function; truncation of MSH3 protein |
| c.2062_2063del (p.Lys688Glufs*2) | Frameshift deletion | 0.01% in general population | Loss of function; premature stop codon |
| c.3133G>A (p.Ala1045Thr) | Missense | 0.05% in cancer cohorts | Uncertain significance; may affect protein stability |
| c.3558_3559insA (p.Glu1187Argfs*5) | Frameshift insertion | 0.01% in Lynch syndrome families | Loss of function; frameshift leading to truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that truncate or destabilize MSH3, impairing MutSβ complex formation and mismatch repair.
Gain of Function (GOF)
No known gain-of-function mutations reported for MSH3.
Dominant Negative (DN)
Rare missense variants may interfere with MSH2 binding, but dominant-negative effects are not well established.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006298 - mismatch repair | • GO:0005524 - ATP binding |
| • GO:0030983 - mismatched DNA binding | • GO:0005634 - nucleus |
| • GO:0006281 - DNA repair |
Pathways
• Mismatch repair (KEGG: hsa03430)
• Colorectal cancer (KEGG: hsa05210)
• Microsatellite instability (Reactome: R-HSA-5358565)
Protein Summary
MSH3 is a 1137-amino acid protein that belongs to the MutS family. It heterodimerizes with MSH2 to form the MutSβ complex, which specifically recognizes insertion/deletion loops (1–15 nucleotides) during DNA mismatch repair. The protein contains an ATPase domain essential for repair signaling. MSH3 deficiency leads to microsatellite instability and is associated with Lynch syndrome and various sporadic cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSH3 Knockout HEK293 Cell Line | EDC07575 | Human | 4437 | Details Get a Quote |
| MSH3 Knockout A-549 Cell Line | EDJ-KQ28274 | Human | 4437 | Details Get a Quote |
| MSH3 Knockout HCT 116 Cell Line | EDJ-KQ28275 | Human | 4437 | Details Get a Quote |
| MSH3 Knockout HeLa Cell Line | EDJ-KQ28276 | Human | 4437 | Details Get a Quote |
| MSH3 (p.A1045T) Point Mutation in HAP1 Cell Line | EDC03553 | Human | 4437 | Details Get a Quote |
| MSH3 (c.1148del )Point Mutation in HAP1 Cell Line | EDC03552 | Human | 4437 | Details Get a Quote |
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