ArticleThe Journal of clinical investigation2014
Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
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- Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.Circulation · 2019Pooled it
- Complications of whole-exome sequencing for causal gene discovery in primary platelet secretion defects.Haematologica · 2019Trial
- Oral Glucose Mobilizes Triglyceride Stores From the Human Intestine.Cellular and molecular gastroenterology and hepatology · 2019Trial
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- Validity of a seven-gene signature as a non-invasive biomarker for cirrhosis: a cross-sectional study in Egyptian patients with HBV infection.BMC gastroenterology · 2026Article
- Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Review
- Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells.bioRxiv : the preprint server for biology · 2025Article
- Uncovering the role of the Hsp40 family member cysteine string protein-α in mouse platelets.Blood advances · 2025Article
- Establishment of a nomogram-based prognostic model (LASSO-Cox regression) for predicting platelet storage lesions under different storage conditions.Frontiers in molecular biosciences · 2025Article
- Pilot proteomic analysis of immune dysregulation in dengue with prior SARS-CoV-2 infection.Frontiers in immunology · 2025Observational
- The syntaxin-binding protein STXBP5 regulates progerin expression.Scientific reports · 2024Article
- Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nature communications · 2024Article
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- Clusterin knockdown has effects on intracellular and secreted von Willebrand factor in human umbilical vein endothelial cells.PloS one · 2024Article
- GENETIC DETERMINANTS OF THROMBOSIS.Transactions of the American Clinical and Climatological Association · 2024Article
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- Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
In humans, vWF levels predict the risk of myocardial infarction and thrombosis; however, the factors that influence vWF levels are not completely understood. Recent genome-wide association studies (GWAS) have identified syntaxin-binding protein 5 (STXBP5) as a candidate gene linked to changes in vWF plasma levels, though the functional relationship between STXBP5 and vWF is unknown. We hypothesized that STXBP5 inhibits endothelial cell exocytosis. We found that STXBP5 is expressed in human endothelial cells and colocalizes with and interacts with syntaxin 4. In human endothelial cells reduction of STXBP5 increased exocytosis of vWF and P-selectin. Mice lacking Stxbp5 had higher levels of vWF in the plasma, increased P-selectin translocation, and more platelet-endothelial interactions, which suggests that STXBP5 inhibits endothelial exocytosis. However, Stxbp5 KO mice also displayed hemostasis defects, including prolonged tail bleeding times and impaired mesenteric arteriole and carotid artery thrombosis. Furthermore, platelets from Stxbp5 KO mice had defects in platelet secretion and activation; thus, STXBP5 inhibits endothelial exocytosis but promotes platelet secretion. Our study reveals a vascular function for STXBP5, validates the functional relevance of a candidate gene identified by GWAS, and suggests that variation within STXBP5 is a genetic risk for venous thromboembolic disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.