MSH5: A Key Player in Meiotic Recombination and DNA Mismatch Repair
Comprehensive gene overview of MSH5, including genomic data, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | MSH5 |
|---|---|
| Full Name | mutS homolog 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 4439 ncbi.nlm.nih.gov/gene/4439 |
| Ensembl ID | ENSG00000112118 |
| UniProt ID | O43196 |
| OMIM ID | 603382 |
| HGNC ID | 7328 |
| Aliases | G7, MUTSH5, hMSH5 |
Description
MSH5 (mutS homolog 5) encodes a protein that forms a heterodimer with MSH4 to facilitate meiotic recombination and crossover formation. It is also involved in DNA mismatch repair and maintenance of genomic stability. The gene is located on chromosome 6p21.33 within the major histocompatibility complex (MHC) region.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary ovarian insufficiency 3 | Defective meiotic recombination due to MSH5 mutations leads to impaired oocyte development and premature ovarian failure. | OMIM #614324; multiple case reports with biallelic MSH5 variants |
| Colorectal cancer | MSH5 variants may contribute to microsatellite instability and tumorigenesis through defective mismatch repair. | COSMIC; ClinVar; association studies |
| Endometrial cancer | Somatic MSH5 mutations observed in endometrial tumors, potentially affecting DNA repair pathways. | COSMIC; TCGA data |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Ovary | 12.3 | Medium |
| Lymph node | 8.7 | Medium |
| Spleen | 6.2 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 | 15.4 | Leukemia cell line; moderate expression |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| A549 | 5.3 | Lung carcinoma; low expression |
| HepG2 | 4.1 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.175G>A (p.Ala59Thr) | Missense | 0.001% (gnomAD) | May affect protein stability; reported in primary ovarian insufficiency |
| c.196C>T (p.Arg66Trp) | Missense | 0.002% (gnomAD) | Associated with meiotic defects; loss of function |
| c.1051C>T (p.Arg351Cys) | Missense | 0.003% (gnomAD) | Reported in colorectal cancer; potential dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) cause primary ovarian insufficiency 3 due to defective meiotic recombination.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported for MSH5.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg351Cys) may act as dominant-negative by disrupting MSH4-MSH5 heterodimer formation.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005524 - ATP binding | • GO:0006298 - mismatch repair |
| • GO:0007131 - reciprocal meiotic recombination | • GO:0030983 - mismatched DNA binding |
| • GO:0048478 - meiotic spindle assembly |
Pathways
• Meiotic recombination (Reactome: R-HSA-912446)
• Mismatch repair (KEGG: hsa03430)
• Homologous recombination (KEGG: hsa03440)
Protein Summary
MSH5 is a 834-amino acid protein belonging to the MutS family. It contains an ATPase domain and forms a heterodimer with MSH4 to promote crossover formation during meiosis. The protein is essential for homologous chromosome pairing and segregation. Mutations in MSH5 are linked to primary ovarian insufficiency and certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSH5 Knockout HEK293 Cell Line | EDJ-KQ3649 | Human | 4439 | Details Get a Quote |
| MSH5 Knockout HeLa Cell Line | EDJ-KQ24241 | Human | 4439 | Details Get a Quote |
| MSH5 Knockout A-549 Cell Line | EDJ-KQ25616 | Human | 4439 | Details Get a Quote |
| MSH5 Knockout HCT 116 Cell Line | EDJ-KQ25617 | Human | 4439 | Details Get a Quote |
| MSH5 Knockout HAP1 Cell Line | EDC08221 | Human | 4439 | Details Get a Quote |
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