STXBP5

Chr 6

syntaxin binding protein 5

Also known as: LGL3, LLGL3, Nbla04300

NCBI Gene: 134957ENSG00000164506UniProt: Q5T5C0

Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

158
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— STXBP5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 115 VUS of 158 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 1.000
Z-score 6.41
OE 0.15 (0.09–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.00Z-score
OE missense 0.66 (0.61–0.71)
401 obs / 609.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.09–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.61–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 10 / 66.3Missense obs/exp: 401 / 609.4Syn Z: 0.18

ClinVar Variant Classifications

158 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS115
Likely Benign22
Benign8
13
Pathogenic
115
VUS
22
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
112
3
0
115
Likely Benign
1
6
3
12
22
Benign
0
2
2
4
8
Total11202116158

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STXBP5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms.
Arias-Vásquez A et al.·Behav Genet
2019Meta-analysis
Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma.
Wang J et al.·Life Sci
2021
Effect of genetic variation in STXBP5 and STX2 on von Willebrand factor and bleeding phenotype in type 1 von Willebrand disease patients.
van Loon JE et al.·PLoS One
2012Cohort
CLEC4M and STXBP5 gene variations contribute to von Willebrand factor level variation in von Willebrand disease.
Sanders YV et al.·J Thromb Haemost
2015
Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.
Zhu QM et al.·Arterioscler Thromb Vasc Biol
2017
The role of genetics in the pathogenesis and diagnosis of type 1 Von Willebrand disease.
Flood VH et al.·Curr Opin Hematol
2019Review
Associations of multiple genetic variations with plasma levels of Von Willebrand Factor and clinical phenotype in Iranian patients with Von Willebrand disease type 1.
Zafarani A et al.·Transfus Apher Sci
2023Cohort
Interaction networks of Weibel-Palade body regulators syntaxin-3 and syntaxin binding protein 5 in endothelial cells.
Schillemans M et al.·J Proteomics
2019
Pseudogene-gene functional networks are prognostic of patient survival in breast cancer.
Smerekanych S et al.·BMC Med Genomics
2020Functional
Transcriptome sequencing uncovers a three-long noncoding RNA signature in predicting breast cancer survival.
Guo W et al.·Sci Rep
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools