MSH4 Gene
MutS Homolog 4: A Key Meiotic Recombination Protein
Gene Information Card
| Symbol | MSH4 |
|---|---|
| Full Name | mutS homolog 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p31.1 |
| NCBI Gene ID | 4438 ncbi.nlm.nih.gov/gene/4438 |
| Ensembl ID | ENSG00000157456 |
| UniProt ID | O15457 |
| OMIM ID | 602105 |
| HGNC ID | 7327 |
| Aliases | MUTSH4 |
Description
MSH4 encodes a member of the DNA mismatch repair (MMR) family, specifically a MutS homolog. Unlike canonical MMR proteins, MSH4 is essential for meiotic recombination and homologous chromosome synapsis. It forms a heterodimer with MSH5 to stabilize Holliday junctions and promote crossover formation during meiosis. MSH4 is highly expressed in testis and ovary, and its dysfunction is linked to meiotic arrest and infertility.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spermatogenic failure 94 (SPGF94) | Biallelic loss-of-function mutations in MSH4 disrupt meiotic recombination, leading to spermatogenic arrest and non-obstructive azoospermia. | ClinVar, OMIM |
| Premature ovarian failure 25 (POF25) | Homozygous or compound heterozygous MSH4 mutations cause meiotic arrest in oocytes, resulting in primary ovarian insufficiency. | ClinVar, OMIM |
| Colorectal cancer (susceptibility) | Rare MSH4 variants may impair DNA repair, but evidence is limited and not fully established. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Ovary | 6.5 | Medium |
| Fallopian tube | 3.1 | Low |
| Breast | 1.8 | Low |
| Prostate | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Seminoma cell line (TCam-2) | 12.5 | Testicular germ cell tumor model |
| Ovarian cancer cell line (OVCAR-3) | 4.3 | Epithelial ovarian cancer |
| HEK 293 | 0.8 | Low expression in embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | Rare | Loss of function; truncation of MSH4 protein |
| c.1765C>T (p.Arg589Trp) | Missense | Rare | Impaired MSH4-MSH5 interaction; meiotic arrest |
| c.2152G>A (p.Gly718Arg) | Missense | Rare | Reduced crossover formation; associated with SPGF94 |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, splice-site) cause meiotic arrest and infertility in both sexes.
Gain of Function (GOF)
No gain-of-function mutations reported for MSH4.
Dominant Negative (DN)
Heterozygous missense variants may exert dominant-negative effects by disrupting MSH4-MSH5 dimerization, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • meiotic DNA double-strand break processing | • meiotic recombination |
| • DNA mismatch repair | • crossover junction endonuclease activity |
| • ATP binding | • protein heterodimerization activity |
Pathways
• Meiotic recombination (Reactome: R-HSA-912446)
• Mismatch repair (KEGG: hsa03430)
• Homologous recombination (KEGG: hsa03440)
Protein Summary
MSH4 is a 936-amino acid protein belonging to the MutS family. It contains an ATPase domain and a DNA-binding domain. MSH4 forms a heterodimer with MSH5 that binds to Holliday junctions and promotes crossover formation during meiosis. The protein is predominantly expressed in germ cells and is essential for proper chromosome segregation. Mutations in MSH4 lead to meiotic arrest and are a known cause of human infertility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MSH4 Knockout HEK293 Cell Line | EDJ-KQ5242 | Human | 4438 | Details Get a Quote |
| MSH4 Knockout HeLa Cell Line | EDJ-KQ53904 | Human | 4438 | Details Get a Quote |
| MSH4 Knockout A-549 Cell Line | EDJ-KQ62395 | Human | 4438 | Details Get a Quote |
| MSH4 Knockout HCT 116 Cell Line | EDJ-KQ70864 | Human | 4438 | Details Get a Quote |
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