MUSK Gene: Muscle-Specific Kinase
Key regulator of neuromuscular junction formation and maintenance
Gene Information Card
| Symbol | MUSK |
|---|---|
| Full Name | muscle associated receptor tyrosine kinase |
| Gene Type | protein coding |
| Chromosomal Location | 9q31.3 |
| NCBI Gene ID | 4593 ncbi.nlm.nih.gov/gene/4593 |
| Ensembl ID | ENSG00000076242 |
| UniProt ID | O15146 |
| OMIM ID | 601296 |
| HGNC ID | 7525 |
| Aliases | CMS9, CMS1C, FADS, MGC126319, MGC126320 |
Description
The MUSK gene encodes muscle-specific kinase (MuSK), a receptor tyrosine kinase essential for the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin-LRP4 signaling and orchestrates the clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane. Mutations in MUSK cause congenital myasthenic syndromes (CMS) with impaired NMJ transmission.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Myasthenic Syndrome 9 (CMS9) | Loss-of-function mutations in MUSK impair agrin-induced AChR clustering, leading to defective neuromuscular transmission. | ClinVar, OMIM |
| Congenital Myasthenic Syndrome 1C (CMS1C) | Mutations in MUSK disrupt MuSK kinase activity or LRP4 binding, causing postsynaptic NMJ defects. | ClinVar, OMIM |
| Fetal Akinesia Deformation Sequence (FADS) | Severe biallelic MUSK mutations result in complete loss of MuSK function, leading to fetal akinesia and arthrogryposis. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | Medium |
| Brain | 1.2 | Low |
| Heart | 0.8 | Low |
| Liver | 0.1 | Not detected |
| Kidney | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RH-30 (rhabdomyosarcoma) | 8.9 | High expression |
| SH-SY5Y (neuroblastoma) | 2.1 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 0.2 | Low expression |
| A549 (lung carcinoma) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.220C>T (p.Arg74Cys) | Missense | Rare | Reduced MuSK phosphorylation and AChR clustering |
| c.755_756delAG (p.Glu252Valfs*12) | Frameshift | Rare | Loss of kinase domain, complete loss of function |
| c.1040G>A (p.Arg347His) | Missense | Rare | Impaired LRP4 binding, dominant negative effect |
| c.1720T>C (p.Tyr574His) | Missense | Rare | Reduced kinase activity, mild CMS phenotype |
Mutation functional classification
Loss of Function (LOF)
Most CMS-associated MUSK mutations are loss-of-function, reducing or abolishing MuSK kinase activity and AChR clustering.
Gain of Function (GOF)
Not reported for MUSK.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg347His) exert dominant-negative effects by interfering with wild-type MuSK function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Agrin-LRP4-MuSK signaling in neuromuscular junction formation
• DOK7-mediated MuSK activation pathway
• Rapsyn-mediated AChR clustering pathway
Protein Summary
MuSK is a single-pass transmembrane receptor tyrosine kinase composed of an extracellular region with four immunoglobulin-like domains and a frizzled-like domain, a transmembrane segment, and an intracellular tyrosine kinase domain. Upon agrin-LRP4 binding, MuSK autophosphorylates and recruits DOK7, which amplifies signaling to induce AChR clustering via rapsyn. MuSK is critical for NMJ formation, maintenance, and synaptic transmission.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MUSK Knockout HEK293 Cell Line | EDJ-KQ5271 | Human | 4593 | Details Get a Quote |
| MUSK Knockout HeLa Cell Line | EDJ-KQ53927 | Human | 4593 | Details Get a Quote |
| MUSK Knockout A-549 Cell Line | EDJ-KQ62419 | Human | 4593 | Details Get a Quote |
| MUSK Knockout HCT 116 Cell Line | EDJ-KQ70887 | Human | 4593 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
