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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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STX3
syntaxin 3
Chromosome 11 Β· 11q12.1
NCBI Gene: 6809Ensembl: ENSG00000166900.17HGNC: HGNC:11438UniProt: A0A0J9YW33
92PubMed Papers
22Diseases
0Drugs
12Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of gene expressionpositive regulation of protein localization to plasma membranepositive regulation of protein localization to cell surfaceplasma membraneretinal dystrophy and microvillus inclusion diseasediarrhea 12, with microvillus atrophymicrovillus inclusion diseaseGenu valgum
✦AI Summary

STX3 (syntaxin 3) is a SNARE protein that functions as a regulator of membrane fusion and gene expression 1. It mediates vesicle docking and fusion processes critical for polarized protein trafficking and secretory autophagy, where autophagosomes fuse with the plasma membrane to secrete cytosolic proteins including inflammatory mediators 2. STX3 localizes to the apical plasma membrane and functions in positive regulation of cell adhesion, protein localization to cell surfaces, and cell population proliferation [GO annotations]. Functionally, STX3 is linked with MYO5B and STXBP2, sharing a common disease mechanism in congenital diarrheal disorders 3. Mutations in STX3 cause microvillus inclusion disease (MVID), a rare autosomal recessive condition characterized by severe chr11 diarrhea, nutrient malabsorption, and failure to thrive, with some patients exhibiting extragastrointestinal manifestations 14. STX3 variants have also been associated with retinal dystrophy and retinal dystrophy with microvillus inclusion disease 4. Additionally, elevated STX3 expression correlates with poor prognosis in esophageal squamous cell carcinoma, suggesting potential oncogenic roles in non-gastrointestinal malignancies 5. STX3 may also link to immune responses, showing inverse expression patterns with IL36G in psoriasis-associated pathways 6.

Sources cited
1
STX3 mutations contribute to variant microvillus inclusion disease and STX3 is a SNARE protein involved in membrane fusion processes
PMID: 32959907
2
STX3 is a member of SNARE proteins controlling secretory autophagy and neuroinflammatory processes
PMID: 38934263
3
STX3 mutations are associated with MVID variants and functionally linked with MYO5B and STXBP2 in a common disease mechanism
PMID: 29266534
4
STX3 variants cause MVID and retinal dystrophy with microvillus inclusion disease; STX3-encoded protein has functionally linked roles in intestinal epithelial cells
PMID: 38307491
5
High STX3 mRNA and protein expression correlate with poor prognosis in esophageal squamous cell carcinoma
PMID: 38014487
6
STX3 is linked to immune gene expression and shows inverse relationship with IL36G in keratinocyte biology
PMID: 35862195
Disease Associationsβ“˜22
retinal dystrophy and microvillus inclusion diseaseOpen Targets
0.63Moderate
diarrhea 12, with microvillus atrophyOpen Targets
0.52Moderate
microvillus inclusion diseaseOpen Targets
0.38Weak
Genu valgumOpen Targets
0.30Weak
Genu varumOpen Targets
0.30Weak
genetic disorderOpen Targets
0.19Weak
adrenal gland hyperfunctionOpen Targets
0.17Weak
Tietze syndromeOpen Targets
0.17Weak
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
neutrophil immunodeficiency syndromeOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
immunodeficiency 86Open Targets
0.04Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
breast cancerOpen Targets
0.04Suggestive
Recurrent infection due to specific granule deficiencyOpen Targets
0.04Suggestive
Visual impairmentOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
lung cancerOpen Targets
0.02Suggestive
Retinal dystrophyOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
Diarrhea 12, with microvillus atrophyUniProt
Retinal dystrophy and microvillus inclusion diseaseUniProt
Pathogenic Variants12
NM_004177.5(STX3):c.438del (p.Arg148fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 148
NM_004177.5(STX3):c.30+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_004177.5(STX3):c.541-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_004177.5(STX3):c.442C>T (p.Arg148Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 148
NM_004177.5(STX3):c.756del (p.Ala253fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 253
NM_004177.5(STX3):c.424C>T (p.Arg142Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 142
NM_004177.5(STX3):c.718_725del (p.Val240fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 240
NM_004177.5(STX3):c.739C>T (p.Arg247Ter)Pathogenic
not provided|Diarrhea 12, with microvillus atrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 247
NM_004177.5(STX3):c.177_178del (p.Tyr60fs)Pathogenic
not provided|Retinal dystrophy and microvillus inclusion disease
β˜…β˜†β˜†β˜†2022β†’ Residue 60
NM_004177.5(STX3):c.115-2A>GPathogenic
Retinal dystrophy and microvillus inclusion disease
β˜†β˜†β˜†β˜†2025
NM_004177.5(STX3):c.363_366delinsGA (p.Val122fs)Pathogenic
Retinal dystrophy and microvillus inclusion disease
β˜†β˜†β˜†β˜†2025β†’ Residue 122
NM_004177.5(STX3):c.372_373dup (p.Arg125fs)Pathogenic
Retinal dystrophy and microvillus inclusion disease
β˜†β˜†β˜†β˜†2021β†’ Residue 125
View on ClinVar β†—
Related Genes
BNIP1Protein interaction100%NSFProtein interaction100%SNAP25Protein interaction100%SNAP23Protein interaction100%VAMP3Protein interaction100%VTI1AProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
98%
Ovary
36%
Heart
30%
Brain
26%
Liver
18%
Gene Interaction Network
Click a node to explore
STX3BNIP1NSFSNAP25SNAP23VAMP3VTI1A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q13277
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.75LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.51 [0.35–0.75]
RankingsWhere STX3 stands among ~20K protein-coding genes
  • #5,219of 20,598
    Most Researched92
  • #2,670of 5,498
    Most Pathogenic Variants12
  • #5,913of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedSTX3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Autozygome and high throughput confirmation of disease genes candidacy.
PMID: 30237576
Genet Med Β· 2019
1.00
2
Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.
PMID: 35862195
JCI Insight Β· 2022
0.90
3
SKArred 2 death: neuroinflammatory breakdown of the hippocampus.
PMID: 38934263
Autophagy Β· 2024
0.80
4
MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update.
PMID: 29266534
Hum Mutat Β· 2018
0.70
5
SNAREs and developmental disorders.
PMID: 32959907
J Cell Physiol Β· 2021
0.60