MSH2 Gene: Mismatch Repair Protein MutS Homolog 2
Key player in DNA mismatch repair, associated with Lynch syndrome and various cancers
Gene Information Card
| Symbol | MSH2 |
|---|---|
| Full Name | mutS homolog 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2p21-p16.1 |
| NCBI Gene ID | 4436 ncbi.nlm.nih.gov/gene/4436 |
| Ensembl ID | ENSG00000095002 |
| UniProt ID | P43246 |
| OMIM ID | 609309 |
| HGNC ID | 7325 |
| Aliases | FCC2, HNPCC, HNPCC1, LYNCH1, COCA1, mutS homolog 2 |
Description
The MSH2 gene encodes a protein that is a critical component of the DNA mismatch repair (MMR) system. It forms heterodimers with MSH6 (MutSα) or MSH3 (MutSβ) to recognize and initiate repair of base-base mismatches and insertion-deletion loops that arise during DNA replication. Defects in MSH2 are associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer) and increased risk for various cancers, including colorectal, endometrial, ovarian, and others. MSH2 also plays roles in DNA damage signaling and apoptosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lynch syndrome (HNPCC) | Germline mutations in MSH2 lead to defective MMR, causing microsatellite instability and increased mutation rate in tumor suppressor genes and oncogenes. | ClinVar, OMIM |
| Muir-Torre syndrome | A variant of Lynch syndrome with sebaceous neoplasms; MSH2 mutations are common. | OMIM, ClinVar |
| Colorectal cancer (sporadic) | Somatic mutations or promoter hypermethylation of MSH2 can cause MMR deficiency in sporadic tumors. | COSMIC, ClinVar |
| Endometrial cancer | MSH2 mutations increase risk; MMR deficiency is a hallmark in a subset of tumors. | ClinVar, COSMIC |
| Ovarian cancer | MSH2 mutations are associated with increased risk, particularly in Lynch syndrome families. | ClinVar |
| Sebaceous gland tumors | Part of Muir-Torre syndrome; MSH2 mutations are frequent. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.7 | Medium |
| Colon | 10.2 | Medium |
| Small intestine | 9.8 | Medium |
| Endometrium | 8.5 | Medium |
| Ovary | 7.9 | Low |
| Stomach | 7.5 | Low |
| Liver | 6.8 | Low |
| Lung | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical adenocarcinoma; high expression |
| MCF7 | 12.8 | Breast adenocarcinoma; moderate |
| A549 | 11.5 | Lung carcinoma; moderate |
| HCT116 | 9.3 | Colorectal carcinoma; MSH2 expressed but MMR deficient due to other mutations |
| K562 | 8.7 | Chronic myelogenous leukemia; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1906G>C (p.Ala636Pro) | Missense | Rare (0.1% in population) | Pathogenic; disrupts MMR function, associated with Lynch syndrome |
| c.942+3A>T | Splice site | Rare | Pathogenic; causes aberrant splicing, loss of function |
| c.2038C>T (p.Arg680Ter) | Nonsense | Rare | Pathogenic; truncating, loss of function |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Pathogenic; loss of translation initiation |
| c.1076+1G>A | Splice donor | Rare | Pathogenic; splicing defect, loss of function |
| c.1786_1787del (p.Leu596GlufsTer2) | Frameshift | Rare | Pathogenic; frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most MSH2 mutations are loss-of-function, leading to defective DNA mismatch repair, microsatellite instability, and increased cancer risk.
Gain of Function (GOF)
No gain-of-function mutations are documented; MSH2 acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with heterodimer formation, but this is not fully established.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • ATP binding |
| • mismatched DNA binding | • protein heterodimerization activity |
| • DNA mismatch repair | • somatic hypermutation of immunoglobulin genes |
| • response to DNA damage stimulus | • cell cycle arrest |
| • apoptotic process |
Pathways
• Mismatch Repair (MMR) pathway
• Lynch syndrome pathway
• Microsatellite instability pathway
• p53 signaling pathway (indirect)
Protein Summary
The MSH2 protein (UniProt P43246) is 934 amino acids long and contains domains for ATP binding, DNA binding, and interaction with MSH6 or MSH3. It forms the MutSα (MSH2-MSH6) and MutSβ (MSH2-MSH3) complexes that recognize mismatches and small loops. MSH2 is essential for MMR, and its loss leads to a mutator phenotype. The protein is localized to the nucleus and is involved in DNA damage response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSH2 Knockout A-549 Cell Line | EDJ-KQ23160 | Human | 4436 | Details Get a Quote |
| MSH2 Knockout HCT 116 Cell Line | EDJ-KQ23161 | Human | 4436 | Details Get a Quote |
| MSH2 Knockout HeLa Cell Line | EDJ-KQ23162 | Human | 4436 | Details Get a Quote |
| Msh2 Knockout SCC7 Cell Line | EDJ-KZ353 | Mouse | 17685 | Details Get a Quote |
| MSH2 (c.1077-80G>A )Point Mutation in HAP1 Cell Line | EDC03550 | Human | 4436 | Details Get a Quote |
| MSH2 (c.1661+12G>A )Point Mutation in HAP1 Cell Line | EDC03551 | Human | 4436 | Details Get a Quote |
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