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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SYN3
synapsin III
Chromosome 22 · 22q12.3
NCBI Gene: 8224Ensembl: ENSG00000185666.16HGNC: HGNC:11496UniProt: O14994
45PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsynaptic vesicle membranesynaptic vesicle clusteringsynapse organizationRetinal dystrophySorsby fundus dystrophyglaucomaage-related macular degeneration
✦AI Summary

Synapsin III (SYN3) is a neuronal protein with dual roles in neurobiology and oncology. In the nervous system, SYN3 is involved in synaptogenesis and regulation of neurotransmitter release 1, functioning at synaptic vesicles to modulate synaptic transmission. In cancer biology, SYN3 uniquely acts as a tumor suppressor in glioblastoma stem cells (GSCs) by promoting neuronal-like transdifferentiation 1. Mechanistically, SYN3 enhances expression of Neuregulin 3, which competitively antagonizes JAG1-Notch1 signaling—a critical pathway maintaining GSC stemness 1. This disruption of Notch signaling reduces self-renewal capacity and drives GSCs toward differentiation. In preclinical glioblastoma models, AAV-mediated SYN3 overexpression significantly impeded tumor progression 1. Clinically, SYN3 has also served as a delivery enhancer: the polyamide compound Syn3 markedly potentiates intravesical adenoviral-mediated gene transfer to bladder epithelium 23, facilitating the FDA-approved nadofaragene firadenovec therapy for BCG-unresponsive bladder cancer 45. These divergent functions highlight SYN3's importance both as a developmental regulator suppressing cancer stemness and as a pharmaceutical excipient enhancing gene delivery.

Sources cited
1
SYN3 promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction through enhanced NRG3 expression
PMID: 39994412
2
Syn3 polyamide compound markedly increases intravesical adenoviral gene transfer and expression in bladder tissue
PMID: 12136430
3
Syn3 enhances intravesical delivery of adenoviral-mediated interferon-alpha gene therapy for bladder cancer with sustained cytokine expression
PMID: 17692556
4
Nadofaragene firadenovec (rAd-IFNα/Syn3) achieves 53.4% complete response in BCG-unresponsive bladder carcinoma in situ with favorable safety profile
PMID: 33253641
5
Nadofaragene firadenovec (rAd-IFNα/Syn3) is FDA-approved gene therapy delivering human interferon alpha-2b gene for BCG-unresponsive non-muscle invasive bladder cancer
PMID: 39131870
Disease Associationsⓘ20
Retinal dystrophyOpen Targets
0.52Moderate
Sorsby fundus dystrophyOpen Targets
0.51Moderate
glaucomaOpen Targets
0.44Moderate
age-related macular degenerationOpen Targets
0.40Weak
Abnormality of the skeletal systemOpen Targets
0.40Weak
retinopathyOpen Targets
0.34Weak
Cerebellar vermis atrophyOpen Targets
0.33Weak
Generalized hypotoniaOpen Targets
0.33Weak
Global developmental delayOpen Targets
0.33Weak
SeizureOpen Targets
0.33Weak
Visual impairmentOpen Targets
0.33Weak
alcohol drinkingOpen Targets
0.32Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.31Weak
macular degenerationOpen Targets
0.30Weak
open-angle glaucomaOpen Targets
0.29Weak
Abruptio PlacentaeOpen Targets
0.29Weak
chronic obstructive pulmonary diseaseOpen Targets
0.28Weak
Cerebral arteriovenous malformationOpen Targets
0.27Weak
COVID-19Open Targets
0.26Weak
joint diseaseOpen Targets
0.23Weak
Pathogenic Variants1
NM_003490.4(SYN3):c.1444_1445delinsTT (p.Pro482Leu)Pathogenic
Global developmental delay;Cerebellar vermis atrophy;Generalized hypotonia;Visual impairment;Seizure
☆☆☆☆→ Residue 482
View on ClinVar ↗
Related Genes
SLC17A7Protein interaction100%VAMP2Protein interaction91%SNCAProtein interaction88%DLG4Protein interaction85%RIC8BProtein interaction84%MARCKSProtein interaction81%
Tissue Expression6 tissues
Brain
100%
Lung
19%
Heart
19%
Ovary
9%
Liver
6%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
SYN3SLC17A7VAMP2SNCADLG4RIC8BMARCKS
PROTEIN STRUCTURE
Preparing viewer…
PDB2P0A · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.54 [0.40–0.72]
RankingsWhere SYN3 stands among ~20K protein-coding genes
  • #9,526of 20,598
    Most Researched45
  • #5,134of 5,498
    Most Pathogenic Variants1
  • #5,593of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedSYN3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.
PMID: 33253641
Lancet Oncol · 2021
1.00
2
Synapsin III promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction.
PMID: 39994412
Neuro Oncol · 2025
0.90
3
Enhancement of intravesical delivery with Syn3 potentiates interferon-alpha2b gene therapy for superficial bladder cancer.
PMID: 17692556
Cytokine Growth Factor Rev · 2007
0.80
4
Syn3 provides high levels of intravesical adenoviral-mediated gene transfer for gene therapy of genetically altered urothelium and superficial bladder cancer.
PMID: 12136430
Cancer Gene Ther · 2002
0.70
5
Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and practical implementation.
PMID: 40970394
Curr Opin Urol · 2025
0.60