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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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STXBP4
syntaxin binding protein 4
Chromosome 17 · 17q22
NCBI Gene: 252983Ensembl: ENSG00000166263.13HGNC: HGNC:19694UniProt: B5MCT9
56PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of cell cycle G1/S phase transitionsyntaxin bindingDNA damage responseextracellular exosomeneurodegenerative diseasebreast carcinomabreast canceraging
✦AI Summary

STXBP4 (syntaxin binding protein 4) is a vesicular trafficking regulator that inhibits SLC2A4 translocation to the plasma membrane by binding STX4A and preventing STX4A-VAMP2 interaction; insulin stimulation disrupts this inhibition, increasing SLC2A4 surface localization 1. Beyond glucose homeostasis, STXBP4 functions as a critical oncogenic regulator in squamous cell carcinomas. STXBP4 suppresses APC/C-mediated proteolysis of the ΔNp63 isoform, a master regulator of basal epidermal identity 2. In lung squamous cell carcinoma, STXBP4 overexpression correlates with ΔNp63 accumulation and drives tumor growth through PDGF receptor signaling; elevated STXBP4 associates with advanced disease stage, pleural involvement, and worse overall survival 3. Germline variants in STXBP4 (rs2628315) at the 17q22 locus associate with breast cancer risk, with preferential G-allele expression linked to increased susceptibility 1. Additionally, STXBP4 upregulation appears in SARS-CoV-2-infected lung tissue within alveolar-bronchiolization lesions, suggesting involvement in aberrant tissue regeneration 4. These findings position STXBP4 as a dual-function protein balancing metabolic regulation with oncogenic potential.

Sources cited
1
STXBP4 (rs2628315) germline allelic expression associates with breast cancer risk; G-allele preferential expression linked to increased BC susceptibility
PMID: 35772352
2
STXBP4 suppresses APC/C-mediated proteolysis of ΔNp63α, inhibits terminal differentiation, and drives oncogenic potential in squamous cell carcinoma
PMID: 29735662
3
STXBP4 drives lung squamous cell carcinoma tumor growth through PDGF receptor signaling; high STXBP4 correlates with advanced T factor, disease stage, pleural involvement, and worse prognosis
PMID: 28087642
4
STXBP4 is upregulated in alveolar-bronchiolization lesions in SARS-CoV-2-infected hamster lungs, suggesting involvement in aberrant tissue regeneration
PMID: 39326207
5
STXBP4 gene variants are computationally predicted to have deleterious effects on breast cancer development through dysregulation of gene expression
PMID: 28422318
6
STXBP4/COX11 rs6504950 polymorphism associates with significantly decreased breast cancer risk in AA/AG genotypes
PMID: 22863968
7
STXBP4 expression predicts worse overall and disease-free survival in lung squamous cell carcinoma through regulation of TP63 (ΔNp63) ubiquitination
PMID: 32993587
8
STXBP4 is identified at a genetic locus associated with epigenetic age acceleration in mice, linking to metabolic and aging pathways
PMID: 35389339
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
breast carcinomaOpen Targets
0.46Moderate
breast cancerOpen Targets
0.39Weak
agingOpen Targets
0.36Weak
ovarian carcinomaOpen Targets
0.33Weak
Abnormality of the skeletal systemOpen Targets
0.33Weak
psoriasisOpen Targets
0.32Weak
breast neoplasmOpen Targets
0.29Weak
clonal hematopoiesisOpen Targets
0.29Weak
luminal A breast carcinomaOpen Targets
0.29Weak
estrogen-receptor positive breast cancerOpen Targets
0.28Weak
hypothyroidismOpen Targets
0.25Weak
prostate carcinomaOpen Targets
0.23Weak
preeclampsiaOpen Targets
0.20Weak
lysosomal storage diseaseOpen Targets
0.10Suggestive
contractureOpen Targets
0.07Suggestive
laryngeal squamous cell carcinomaOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.05Suggestive
intestinal hypomagnesemia 1Open Targets
0.04Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
VAMP2Protein interaction100%SLC2A4Protein interaction79%STX4Protein interaction79%SNAP23Protein interaction79%HERC2Shared pathway20%MCM8Shared pathway17%
Tissue Expression6 tissues
Ovary
100%
Lung
72%
Heart
43%
Liver
38%
Brain
31%
Bone Marrow
27%
Gene Interaction Network
Click a node to explore
STXBP4VAMP2SLC2A4STX4SNAP23HERC2MCM8
PROTEIN STRUCTURE
Preparing viewer…
PDB2YSG · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.57–1.04]
RankingsWhere STXBP4 stands among ~20K protein-coding genes
  • #8,141of 20,598
    Most Researched56
  • #10,349of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedSTXBP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association of STXBP4/COX11 rs6504950 (G>A) polymorphism with breast cancer risk: evidence from 17,960 cases and 22,713 controls.
PMID: 22863968
Arch Med Res · 2012
1.00
2
Computational Analysis of Breast Cancer GWAS Loci Identifies the Putative Deleterious Effect of STXBP4 and ZNF404 Gene Variants.
PMID: 28422318
J Cell Biochem · 2017
0.90
3
Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters.
PMID: 39326207
EBioMedicine · 2024
0.80
4
STXBP4 regulates APC/C-mediated p63 turnover and drives squamous cell carcinogenesis.
PMID: 29735662
Proc Natl Acad Sci U S A · 2018
0.70
5
STXBP4 Drives Tumor Growth and Is Associated with Poor Prognosis through PDGF Receptor Signaling in Lung Squamous Cell Carcinoma.
PMID: 28087642
Clin Cancer Res · 2017
0.60