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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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STXBP6
syntaxin binding protein 6
Chromosome 14 · 14q12
NCBI Gene: 29091Ensembl: ENSG00000168952.17HGNC: HGNC:19666UniProt: Q8NFX7
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
SNARE complex assemblycadherin binding involved in cell-cell adhesionadherens junctionnegative regulation of exocytosiscataractmigraine disorderAbnormality of the skeletal systemfunctional neutrophil defect
✦AI Summary

STXBP6 (syntaxin binding protein 6) is a SNARE complex component that regulates neuronal and cellular exocytosis by forming non-fusogenic complexes with SNAP25 and STX1A, thereby modulating functional SNARE complex assembly and negatively regulating exocytosis 1. Beyond its classical vesicle trafficking role, STXBP6 exhibits pleiotropic functions across multiple disease contexts. In neurology, STXBP6 mutations cause developmental epileptic encephalopathy and autism spectrum disorders through disrupted synaptic vesicle exocytosis 1. In autoimmunity, STXBP6 represents a genetic risk factor for type 1 diabetes, particularly late-onset disease; proinflammatory cytokines upregulate STXBP6 expression, which impairs insulin secretion and increases beta cell apoptosis 2. STXBP6 also associates with immunoglobulin A deficiency in HLA-risk allele carriers 3 and Parkinson disease dementia 4. In cancer biology, STXBP6 functions as an oncogenic driver, promoting ovarian cancer growth and metastasis through PI3K/AKT-dependent lipid metabolism reprogramming 5. Additionally, STXBP6 negatively regulates PD-L1 expression via IRF1 cytoplasmic retention, forming a positive feedback loop that modulates anti-tumor immunity 6. STXBP6 methylation patterns correlate with non-small cell lung cancer stage and patient survival 7.

Sources cited
1
STXBP6 is essential for SNARE complex function in neuronal vesicle trafficking; mutations cause developmental epileptic encephalopathy and autism spectrum disorders
PMID: 38003627
2
STXBP6 is upregulated by T1D-related proinflammatory cytokines and impairs insulin secretion and increases beta cell apoptosis in late-onset T1D
PMID: 39227839
3
STXBP6 genetic variation associates with IgA deficiency in carriers of HLA risk alleles
PMID: 34976003
4
STXBP6 has strong diagnostic value for Parkinson disease dementia
PMID: 40355913
5
STXBP6 promotes ovarian cancer growth and metastasis through PI3K/AKT-dependent fatty acid oxidation and lipid metabolism reprogramming
PMID: 41160169
6
STXBP6 negatively regulates PD-L1 expression by retaining IRF1 in cytoplasm; forms positive feedback loop with IRF1 affecting T cell activation
PMID: 32700091
7
STXBP6 methylation patterns correlate with non-small cell lung cancer stage, tumor diameter, and patient survival
PMID: 35818250
Disease Associationsⓘ20
cataractOpen Targets
0.32Weak
migraine disorderOpen Targets
0.32Weak
Abnormality of the skeletal systemOpen Targets
0.31Weak
functional neutrophil defectOpen Targets
0.31Weak
diabetes mellitusOpen Targets
0.30Weak
obesityOpen Targets
0.29Weak
type 2 diabetes mellitusOpen Targets
0.27Weak
sexually transmitted diseaseOpen Targets
0.27Weak
tooth diseaseOpen Targets
0.27Weak
overnutritionOpen Targets
0.25Weak
metabolic syndromeOpen Targets
0.20Weak
kidney diseaseOpen Targets
0.19Weak
mental or behavioural disorderOpen Targets
0.17Weak
skin cancerOpen Targets
0.17Weak
tricuspid valve diseaseOpen Targets
0.17Weak
hypertrophic cardiomyopathyOpen Targets
0.17Weak
response to antihypertensive drugOpen Targets
0.17Weak
non-small cell lung carcinomaOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.04Suggestive
ependymomaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
VAMP8Protein interaction100%NAPAProtein interaction99%STXBP5Protein interaction95%SNAP25Protein interaction93%SLC22A17Protein interaction83%COCHProtein interaction83%
Tissue Expression6 tissues
Heart
100%
Brain
93%
Lung
72%
Liver
13%
Ovary
11%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
STXBP6VAMP8NAPASTXBP5SNAP25SLC22A17COCH
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NFX7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.55–1.12]
RankingsWhere STXBP6 stands among ~20K protein-coding genes
  • #13,086of 20,598
    Most Researched25
  • #11,509of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedSTXBP6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrating plasma circulating protein-centered multi-omics to identify potential therapeutic targets for Parkinsonian cognitive disorders.
PMID: 40355913
J Transl Med · 2025
1.00
2
A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression.
PMID: 39227839
BMC Med · 2024
0.90
3
STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy.
PMID: 38003627
Int J Mol Sci · 2023
0.80
4
PMID: 34976003
Front Genet · 2021
0.70
5
Significance of screening sensitive methylation sites using whole-genome sequencing in early diagnosis of non-small cell lung cancer.
PMID: 35818250
Cell Mol Biol (Noisy-le-grand) · 2022
0.60