STXBP1

Chr 9ADAR

syntaxin binding protein 1

Also known as: DEE4, MUNC18-1, N-Sec1, NSEC1, P67, RBSEC1, UNC18, unc-18A

NCBI Gene: 6812ENSG00000136854UniProt: P61764OMIM: 602926

This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 4MIM #612164
ADAR

Clinical highlights

Management implications
STXBP1 has therapies in development
Gene-disease validity (ClinGen)
genetic developmental and epileptic encephalopathy · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
87
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.09
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — STXBP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
  • STXBP1-upregulation ASO programs
    ASOPhase 1

    Boost STXBP1 expression from the intact allele (haploinsufficiency).

    Delivery: Intrathecal

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.09LOEUF
pLI 1.000
Z-score 5.46
OE 0.00 (0.00–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.26Z-score
OE missense 0.36 (0.31–0.42)
127 obs / 352.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.09)
0≤0.351.4
Missense OE?0.36 (0.31–0.42)
0≤0.61.4
Synonymous OE?0.90
0≤1.21.6
LoF obs/exp: 0 / 34.7Missense obs/exp: 127 / 352.1Syn Z: 0.96

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients