STXBP1
Chr 9ADARsyntaxin binding protein 1
Also known as: DEE4, MUNC18-1, N-Sec1, NSEC1, P67, RBSEC1, UNC18, unc-18A
The syntaxin-binding protein regulates neurotransmitter release by controlling syntaxin, a transmembrane receptor protein essential for synaptic vesicle fusion. Mutations cause developmental and epileptic encephalopathy 4, inherited in autosomal dominant or recessive patterns, predominantly through loss-of-function mechanisms that disrupt synaptic transmission. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as a primary disease mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
STXBP1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGA Multicentric European Study to Promote Clinical Trial Readiness for STXBP1-related Disorders
RECRUITINGPhenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
ACTIVE NOT RECRUITINGPhenotyping and Identification of Biological Markers in STXBP1 Encephalopathy
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools