DOK7 Gene: Docking Protein 7
Key Regulator of Neuromuscular Junction Formation and Congenital Myasthenic Syndromes
Gene Information Card
| Symbol | DOK7 |
|---|---|
| Full Name | Docking Protein 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 285489 ncbi.nlm.nih.gov/gene/285489 |
| Ensembl ID | ENSG00000138650 |
| UniProt ID | Q6IB77 |
| OMIM ID | 610285 |
| HGNC ID | 26594 |
| Aliases | CMS1B, FLJ45717, MGC131895 |
Description
The DOK7 gene encodes docking protein 7, a cytoplasmic adaptor protein essential for the formation and maintenance of the neuromuscular junction (NMJ). DOK7 interacts with the muscle-specific kinase (MuSK) to initiate and stabilize acetylcholine receptor clustering at the postsynaptic membrane. Mutations in DOK7 are a common cause of congenital myasthenic syndrome (CMS), particularly the limb-girdle type, and can also be associated with other neuromuscular disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Myasthenic Syndrome 1B (CMS1B) | Loss-of-function mutations in DOK7 impair MuSK activation and AChR clustering, leading to defective neuromuscular transmission. | ClinVar, OMIM |
| Congenital Myasthenic Syndrome with Tubular Aggregates | DOK7 mutations disrupt NMJ maintenance, causing muscle weakness and tubular aggregates on biopsy. | OMIM, PubMed |
| Myasthenia Gravis (seronegative) | Rare DOK7 variants may contribute to autoimmune-negative myasthenic phenotypes. | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | 12.5 | Medium |
| Heart | 8.3 | Low |
| Brain | 3.1 | Low |
| Liver | 0.9 | Not detected |
| Kidney | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RD (rhabdomyosarcoma) | 15.0 | Highest expression among tested lines |
| SH-SY5Y (neuroblastoma) | 6.2 | Moderate expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124_1127dupTGCC | Duplication | ~30% of CMS1B cases | Frameshift, loss of function |
| c.1327C>T (p.Arg443*) | Nonsense | ~10% of CMS1B cases | Premature stop, loss of function |
| c.331G>A (p.Gly111Arg) | Missense | Rare | Impaired MuSK binding, loss of function |
| c.1393G>A (p.Gly465Arg) | Missense | Rare | Reduced protein stability, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most DOK7 mutations are loss-of-function, leading to reduced or absent protein expression or impaired interaction with MuSK, resulting in defective neuromuscular junction formation and congenital myasthenic syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DOK7.
Dominant Negative (DN)
Some missense mutations (e.g., p.Gly111Arg) may exert a dominant-negative effect by interfering with wild-type DOK7 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Agrin-MuSK-DOK7 signaling in neuromuscular junction formation (Reactome: R-HSA-6794362)
• DOK7-mediated AChR clustering (KEGG: hsa04730)
Protein Summary
Docking protein 7 (DOK7) is a 504-amino-acid cytoplasmic adaptor protein containing a pleckstrin homology (PH) domain and a phosphotyrosine-binding (PTB) domain. It is predominantly expressed in skeletal muscle and localizes to the postsynaptic membrane of the neuromuscular junction. DOK7 binds to the intracellular region of MuSK, promoting its autophosphorylation and downstream signaling that leads to acetylcholine receptor clustering. Loss of DOK7 function results in impaired NMJ formation and congenital myasthenic syndrome.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOK7 Knockout HEK293 Cell Line | EDJ-KQ13199 | Human | 285489 | Details Get a Quote |
| DOK7 Knockout HeLa Cell Line | EDJ-KQ41339 | Human | 285489 | Details Get a Quote |
| DOK7 Knockout A-549 Cell Line | EDJ-KQ67984 | Human | 285489 | Details Get a Quote |
| DOK7 Knockout HCT 116 Cell Line | EDJ-KQ76360 | Human | 285489 | Details Get a Quote |
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