Affinage

SYN2

Synapsin-2 · UniProt Q92777

Length
582 aa
Mass
63.0 kDa
Annotated
2026-04-28
12 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SYN2 encodes a neuron-specific phosphoprotein associated with synaptic vesicles that regulates synaptic vesicle cycling and axon outgrowth (PMID:23956174). The human SYN2 gene maps to chromosome 3p, distinct from the X-linked SYN1 paralog (PMID:7587399). Loss-of-function mutations (nonsense and missense) in SYN2 abolish rescue of the SYN2 knockout neuronal phenotype, demonstrating that intact Synapsin II is required for normal synaptogenesis and neurotransmitter release (PMID:23956174).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 1995 High

    Chromosomal mapping resolved SYN2 as an autosomal locus on human chromosome 3p (and mouse chromosome 6F), establishing it as a distinct synapsin family member separate from X-linked SYN1.

    Evidence PCR from somatic hybrid cell lines, FISH, and backcross genotyping in human and mouse

    PMID:7587399

    Open questions at the time
    • No functional data provided at this stage
    • Tissue-specific expression pattern not characterized beyond neuron-specific designation
  2. 2013 Medium

    Functional rescue experiments established that SYN2 directly regulates synaptic vesicle cycling and axon outgrowth, as wild-type human Synapsin II restored these functions in SYN2 knockout neurons while disease-associated missense mutants (Y236S, G464R) failed to rescue.

    Evidence Expression of wild-type and mutant human SYN2 in SYN2 knockout mouse neurons, with synaptic vesicle cycling assays and axon outgrowth measurements

    PMID:23956174

    Open questions at the time
    • Single-lab study; independent replication in additional systems not reported
    • Biochemical mechanism by which missense mutations disrupt vesicle cycling is not determined
    • Phosphorylation-dependent regulation of Synapsin II function not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise molecular mechanism by which Synapsin II tethers or regulates synaptic vesicles, the identity of its critical binding partners at the vesicle surface, and the functional consequences of its phosphorylation remain unresolved.
  • No structural model of Synapsin II–vesicle interactions
  • No systematic identification of direct protein interaction partners
  • Role of individual phosphorylation sites in vesicle cycling not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Loss-of-function mutations in SYN2 (nonsense A94fs199X and missense Y236S, G464R) impair synaptic vesicle cycling and axon outgrowth; wild-type human Syn II rescues the SYN2 knockout phenotype in neurons, while the nonsense mutant is not expressed and missense mutants fail to rescue, establishing SYN2 as a regulator of synaptic vesicle cycling and synaptogenesis. Functional rescue assay in SYN2 knockout neurons (expression of wild-type and mutant human SYN2), synaptic vesicle cycling assays, axon outgrowth measurements Human molecular genetics Medium 23956174
1995 The human SYN2 gene was mapped to chromosome 3p and the mouse Syn2 gene to chromosome 6 band F, establishing SYN2 as a neuron-specific phosphoprotein gene on autosomes distinct from the X-linked SYN1. PCR amplification from somatic hybrid cell lines, single-strand conformation analysis, FISH, and backcross genotyping Cytogenetics and cell genetics High 7587399

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science (New York, N.Y.) 152 28280153
2013 SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth. Human molecular genetics 68 23956174
2005 Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia. Behavioral and brain functions : BBF 67 16131404
2011 The enantiomers of syn-2,3-difluoro-4-aminobutyric acid elicit opposite responses at the GABA(C) receptor. Chemical communications (Cambridge, England) 34 22143050
2019 Syn-2, 3-diols and anti-inflammatory indole derivatives from Streptomyces sp. CB09001. Natural product research 12 31135217
2019 A case of nasal low-grade non-intestinal-type adenocarcinoma with aberrant CDX2 expression and a novel SYN2-PPARG gene fusion in a 13-year-old girl. Virchows Archiv : an international journal of pathology 9 30666415
2011 Lack of association between synapsin II (SYN2) gene polymorphism and susceptibility epilepsy: a case-control study and meta-analysis. Synapse (New York, N.Y.) 9 21465568
1995 Mapping of synapsin II (SYN2) genes to human chromosome 3p and mouse chromosome 6 band F. Cytogenetics and cell genetics 8 7587399
2023 Small cell lung cancer with SYN2::PPARG fusion. Pathology, research and practice 2 38238071
2026 Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass C with SYN2::PPARG fusion in an older adult. CNS oncology 0 41877551
2026 High-Grade Acinic Cell Carcinoma of the Parotid with SYN2::PPARG Fusion. Head and neck pathology 0 42008002
2024 A Case of Acinic Cell Carcinoma with SYN2::PPARG Fusion. Head and neck pathology 0 39417931