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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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STXBP3
syntaxin binding protein 3
Chromosome 1 Β· 1p13.3
NCBI Gene: 6814Ensembl: ENSG00000116266.12HGNC: HGNC:11446UniProt: O00186
89PubMed Papers
20Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsyntaxin bindingneutrophil degranulationnegative regulation of calcium ion-dependent exocytosissensorineural hearing losshypothyroidismGenu varumGenu valgum
✦AI Summary

STXBP3 (syntaxin binding protein 3) is a vesicular trafficking protein that regulates intracellular transport and exocytosis. Primary function: STXBP3 participates in insulin-dependent GLUT4 glucose transporter trafficking to the plasma membrane in adipocytes, working alongside STX4 and VAMP2 to mediate vesicle docking and fusion 1. Mechanism: The protein regulates syntaxin-dependent vesicle trafficking and maintains submembrane F-actin networks critical for secretory processes 2. Disease relevance: STXBP3 variants are associated with very early onset inflammatory bowel disease (VEOIBD), bilateral sensorineural hearing loss, and immune dysregulation; loss-of-function mutations impair intestinal epithelial cell polarity and immune function 3. Genetic variants in STXBP3 are linked to incident myocardial infarction, controlling GLUT4 trafficking to plasma membrane 4. STXBP3 expression is elevated in acute allograft rejection and correlates with immunological status 5. Clinical significance: STXBP3 and GOT2 show promising diagnostic potential for early-stage acute allograft rejection 5. STXBP3 genetic variants associate with subcutaneous adipose tissue distribution in HIV-infected patients, linking metabolism and inflammatory pathways 6. The protein interacts with mitochondrial dysfunction pathways relevant to diabetic cardiomyopathy 7.

Sources cited
1
STXBP3 variants cause very early onset IBD, sensorineural hearing loss, immune dysregulation, and regulate intracellular vesicular trafficking
PMID: 33891011
2
STXBP3 expression is elevated in acute allograft rejection and has diagnostic value for early-stage AR
PMID: 36532048
3
STXBP3 variants are associated with incident myocardial infarction and control GLUT4 trafficking
PMID: 38062110
4
STXBP3 is involved in insulin-stimulated GLUT4 translocation from intracellular vesicles to cell surface
PMID: 15690075
5
MUNC18 proteins including STXBP3 regulate vesicle trafficking and F-actin networks
PMID: 31719162
6
STXBP3 is associated with glucose metabolism in adipocytes and subcutaneous adipose tissue distribution
PMID: 21897333
7
STXBP3 interacts with hub genes in mitochondrial dysfunction pathways relevant to diabetic cardiomyopathy
PMID: 40748624
8
STXBP3 protein interacts with UCHL1 in mitochondrial dysfunction-related networks
PMID: 40790764
Disease Associationsβ“˜20
sensorineural hearing lossOpen Targets
0.42Moderate
hypothyroidismOpen Targets
0.28Weak
Genu varumOpen Targets
0.28Weak
Genu valgumOpen Targets
0.27Weak
ovarian carcinomaOpen Targets
0.15Weak
immune dysregulation, autoimmunity, and autoinflammationOpen Targets
0.15Weak
MODYOpen Targets
0.10Suggestive
type 2 diabetes mellitusOpen Targets
0.09Suggestive
type 1 diabetes mellitusOpen Targets
0.09Suggestive
diabetes mellitusOpen Targets
0.08Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.06Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 2Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.06Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.06Suggestive
Acanthosis nigricans - Insulin resistance - muscle cramps - acral enlargementOpen Targets
0.06Suggestive
acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndromeOpen Targets
0.06Suggestive
synovial sarcomaOpen Targets
0.06Suggestive
pancreatic beta cell agenesis with neonatal diabetes mellitusOpen Targets
0.06Suggestive
Pathogenic Variants3
NM_007269.4(STXBP3):c.1029+1_1029+5delLikely pathogenic
STXBP3-related disorders
β˜…β˜†β˜†β˜†2024
NM_007269.4(STXBP3):c.622G>A (p.Ala208Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 208
NM_007269.4(STXBP3):c.1029+2T>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
SNAP23Protein interaction100%SNAP25Protein interaction100%EXOC7Protein interaction100%EXOC6Protein interaction100%EXOC4Protein interaction100%EXOC1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
69%
Heart
63%
Lung
62%
Ovary
57%
Liver
51%
Gene Interaction Network
Click a node to explore
STXBP3SNAP23SNAP25EXOC7EXOC6EXOC4EXOC1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O00186
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.55 [0.40–0.77]
RankingsWhere STXBP3 stands among ~20K protein-coding genes
  • #5,381of 20,598
    Most Researched89
  • #4,003of 5,498
    Most Pathogenic Variants3
  • #6,289of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedSTXBP3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
STXBP3 and GOT2 predict immunological activity in acute allograft rejection.
PMID: 36532048
Front Immunol Β· 2022
1.00
2
Integrated omics analysis of coronary artery calcifications and myocardial infarction: the Framingham Heart Study.
PMID: 38062110
Sci Rep Β· 2023
0.90
3
The mitochondrial hub gene UCHL1 May serve as a potential biomarker for diagnosing diabetic cardiomyopathy: a comprehensive integration of biological pathways.
PMID: 40790764
BMC Med Genomics Β· 2025
0.80
4
Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.
PMID: 33891011
J Crohns Colitis Β· 2021
0.70
5
MUNC18-1 regulates the submembrane F-actin network, independently of syntaxin1 targeting, via hydrophobicity in Ξ²-sheet 10.
PMID: 31719162
J Cell Sci Β· 2019
0.60