STXBP1 (Syntaxin Binding Protein 1)
A key regulator of synaptic vesicle fusion; mutations cause STXBP1 encephalopathy with epilepsy.
Gene Information Card
| Symbol | STXBP1 |
|---|---|
| Full Name | Syntaxin binding protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.11 |
| NCBI Gene ID | 6812 ncbi.nlm.nih.gov/gene/6812 |
| Ensembl ID | ENSG00000136854 |
| UniProt ID | P61764 |
| OMIM ID | 602926 |
| HGNC ID | 11444 |
| Aliases | MUNC18-1, MUNC18, NSEC1, p67, Unc18-1 |
Description
The STXBP1 gene encodes syntaxin-binding protein 1 (also known as MUNC18-1), a neuron-specific protein essential for synaptic vesicle docking and fusion. It binds to syntaxin 1A and regulates SNARE complex assembly, thereby controlling neurotransmitter release. Mutations in STXBP1 are a major cause of early infantile epileptic encephalopathy (EIEE) and other neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| STXBP1 encephalopathy (early infantile epileptic encephalopathy type 4) | Haploinsufficiency due to loss-of-function mutations (nonsense, frameshift, splice site) or missense mutations that impair protein stability or function, leading to reduced MUNC18-1 levels and impaired synaptic transmission. | ClinVar; OMIM #612164; multiple case reports |
| Ohtahara syndrome (early infantile epileptic encephalopathy) | De novo mutations (mostly missense) that disrupt MUNC18-1 function, causing severe epilepsy with suppression-burst EEG pattern. | OMIM #308350; literature (e.g., Saitsu et al., 2008) |
| Intellectual disability with or without epilepsy | Pathogenic variants leading to partial loss of function, affecting cognitive development. | ClinVar; Deciphering Developmental Disorders study |
| Parkinson's disease (rare association) | Altered STXBP1 expression or function may affect dopaminergic neurotransmission, but evidence is limited. | UniProt; some case-control studies (not definitive) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 20.3 | High |
| Cerebral cortex | 25.1 | High |
| Cerebellum | 18.7 | High |
| Testis | 4.2 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal-like |
| U-87 MG (glioblastoma) | 8.4 | Moderate |
| HEK 293 | 1.1 | Low |
| HeLa | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.895C>T (p.Arg299Ter) | Nonsense | Rare (de novo) | Loss of function; premature truncation, likely nonsense-mediated decay |
| c.1699A>G (p.Lys567Glu) | Missense | Rare (de novo) | Disrupts syntaxin binding; reduced protein stability |
| c.1292T>C (p.Leu431Pro) | Missense | Rare (de novo) | Impairs MUNC18-1 folding and function |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Loss of translation initiation; complete loss of protein |
Mutation functional classification
Loss of Function (LOF)
Most STXBP1 mutations are loss-of-function, leading to haploinsufficiency. This is the primary mechanism in STXBP1 encephalopathy.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; some missense variants may have dominant-negative effects but are not classic gain-of-function.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg292His) may exert dominant-negative effects by interfering with wild-type MUNC18-1 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • SNARE binding | • syntaxin binding |
| • protein binding | • regulation of synaptic vesicle exocytosis |
| • synaptic vesicle priming | • neurotransmitter secretion |
| • vesicle fusion |
Pathways
• SNARE complex assembly
• Synaptic vesicle cycle
• Neurotransmitter release
Protein Summary
MUNC18-1 (STXBP1) is a 67 kDa protein that binds to syntaxin 1A in a closed conformation, stabilizing it and preventing premature SNARE complex formation. It also participates in vesicle docking and priming, and is crucial for calcium-triggered neurotransmitter release. Loss of MUNC18-1 leads to severe synaptic dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STXBP1 Knockout HEK293 Cell Line | EDJ-KQ5866 | Human | 6812 | Details Get a Quote |
| STXBP1 Knockout HeLa Cell Line | EDJ-KQ28084 | Human | 6812 | Details Get a Quote |
| STXBP1 Knockout A-549 Cell Line | EDJ-KQ29351 | Human | 6812 | Details Get a Quote |
| STXBP1 Knockout HCT 116 Cell Line | EDJ-KQ29352 | Human | 6812 | Details Get a Quote |
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