SYNA — Synapsin I

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SYNA — Synapsin I

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SYNA — Synapsin I

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SYNA — Synapsin I</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SYNA</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Synapsin I</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/6853" target="_blank">6853</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000135547" target="_blank">ENSG00000135547</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/313440" target="_blank">313440</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P17600" target="_blank">P17600</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Epilepsy, Schizophrenia</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum), [neurons](/entities/neurons)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>

SYNA — Synapsin I

Overview

...

SYNA — Synapsin I

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SYNA — Synapsin I</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SYNA</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Synapsin I</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/6853" target="_blank">6853</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000135547" target="_blank">ENSG00000135547</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/313440" target="_blank">313440</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P17600" target="_blank">P17600</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Epilepsy, Schizophrenia</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum), [neurons](/entities/neurons)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>

SYNA — Synapsin I

Overview

SYNA (Synapsin I) is a neuronal phosphoprotein associated with the cytoplasmic surface of synaptic vesicles. It plays essential roles in synaptogenesis, neurotransmitter release, and synaptic plasticity. The SYNA gene encodes synapsin I, a member of the synapsin family of synaptic vesicle-associated proteins that are critical for proper synaptic function. [@greengard1999]

Synapsins are a family of neuronal phosphoproteins (SYN1, SYN2, SYN3) that dynamically associate with synaptic vesicles. Synapsin I, the most studied member, is involved in regulating the reserve pool of synaptic vesicles, maintaining synaptic transmission, and supporting synaptic plasticity. [@deveaud2008]

Gene and Protein Structure

Gene Organization

The SYNA gene is located on chromosome 17q21.31 and spans approximately 35 kb. It contains multiple exons that undergo alternative splicing to produce multiple isoforms:

Synapsin Ia: 706 amino acids
Synapsin Ib: 669 amino acids (lacking domain E)

Protein Domains

Synapsin I contains several functional domains:

Domain A (N-terminus): Mediation of synaptic vesicle clustering
Domain B: Proline-rich region, protein-protein interactions
Domain C: Membrane interaction domain
Domain D: ATP-binding domain (important for function)
Domain E (C-terminus): Regulatory phosphorylation sites

The protein has an elongated structure with multiple phosphorylation sites that regulate its function in response to neuronal activity. [@brenman1998]

Function

Normal Physiological Function

Synaptic Vesicle Organization

Synapsin I plays a critical role in organizing synaptic vesicles:

Reserve pool maintenance: Synapsin I tethers synaptic vesicles to the actin cytoskeleton in the reserve pool
Vesicle trafficking: Facilitates movement of vesicles between pools
Synaptic assembly: Critical for synaptogenesis during development

Regulation of Neurotransmitter Release

Synapsin I modulates neurotransmitter release through multiple mechanisms:

Vesicle availability: Controls the number of vesicles available for release
Release probability: Influences the probability of synaptic vesicle release
Short-term plasticity: Contributes to synaptic depression and facilitation

The phosphorylation state of synapsin I is a key regulator of its function. Activity-dependent phosphorylation by PKA, CaMKII, and MAPK modulates synaptic vesicle release. [@hilfiker1998]

Synaptic Plasticity

Synapsin I is implicated in various forms of synaptic plasticity:

Long-term potentiation (LTP): Modulates excitatory synaptic transmission
Long-term depression (LTD): Regulates synaptic weakening
Homeostatic plasticity: Contributes to synaptic scaling

Expression Pattern

SYNA is expressed in Brain ([cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum) and is exclusively neuronal. Expression is:

Developmental regulation: High expression during synaptogenesis, decreased in adulthood
Region-specific: Enriched in excitatory synapses of the hippocampus and cortex
Activity-dependent: Expression levels are modulated by neuronal activity

In the brain, synapsin I is primarily localized to presynaptic terminals where it associates with the cytoplasmic surface of synaptic vesicles. [@takamori2006]

Disease Associations

Alzheimer's Disease

In [Alzheimer's disease](/diseases/alzheimers-disease/), synapsin I shows significant alterations:

Reduced expression: Synapsin I levels are decreased in AD brain, particularly in the hippocampus
Phosphorylation changes: Altered phosphorylation patterns affect synaptic vesicle function
Synaptic loss: Synapsin loss correlates with cognitive decline
Interaction with amyloid-beta: Synapsin I interacts with [amyloid-beta](/proteins/amyloid-beta) and may modulate its toxicity

Synapsin I loss is one of the earliest markers of synaptic dysfunction in AD, preceding overt neuronal loss. [@klemmer2011]

Key mechanisms:

Amyloid-beta accumulation leads to synapsin I degradation

Loss of synapsin I disrupts synaptic vesicle pools

Impaired neurotransmitter release contributes to synaptic failure

Creates a positive feedback loop of synaptic dysfunction

Parkinson's Disease

In [Parkinson's disease](/diseases/parkinsons-disease), synapsin I is implicated in:

Dopaminergic neuron dysfunction: Synapsin I in substantia nigra dopaminergic neurons
Alpha-synuclein interaction: [Alpha-synuclein](/proteins/alpha-synuclein) pathology affects synapsin I function
Synaptic dysfunction: Early synaptic changes in PD models

Synapsin I alterations in PD may contribute to the characteristic synaptic dysfunction that precedes dopaminergic neuron loss. [@garden2002]

Epilepsy

Synapsin I mutations and alterations are associated with epilepsy:

Synapsinopathies: Mutations in SYNA cause familial epilepsy
Altered vesicle dynamics: Changes in neurotransmitter release contribute to hyperexcitability
Therapeutic implications: Synapsin-based therapies are being explored

Epilepsy-associated mutations in synapsin I disrupt synaptic vesicle function and lead to neuronal hyperexcitability. [@porten2010]

Schizophrenia

Synapsin I alterations have been reported in schizophrenia:

Expression changes: Reduced synapsin I in prefrontal cortex
Polymorphisms: Genetic variants associated with schizophrenia risk
Synaptic dysfunction: Contributes to the cognitive deficits characteristic of schizophrenia

Synapsin I dysregulation may be part of the broader synaptic pathology in schizophrenia. [@miksa2009]

Lewy Body Diseases

In Lewy body diseases including [dementia with Lewy bodies](/diseases/dementia-lewy-bodies), synapsin I shows:

Colocalization with Lewy bodies: Synapsin I is found in Lewy bodies
Presynaptic pathology: Early disruption of presynaptic function
Interaction with alpha-synuclein: Synapsin I interacts with aggregated alpha-synuclein

Synapsin alterations contribute to the characteristic synaptic dysfunction in these disorders. [@ferrer2017]

Other Neurodegenerative Disorders

Frontotemporal dementia: Synapsin I alterations in specific subtypes
Huntington's disease: Synapsin changes in striatum
Amyotrophic lateral sclerosis: Motor neuron synaptic dysfunction

Therapeutic Implications

Therapeutic Strategies

Synapsin upregulation: Small molecules or gene therapy to increase synapsin expression

Phosphorylation modulators: Agents that normalize synapsin phosphorylation

Synaptic protectors: Compounds that preserve synaptic function

Gene therapy: Viral vector delivery of functional SYNA

Biomarker Potential

Synapsin I has potential as a biomarker:

Cerebrospinal fluid: Synapsin I levels in CSF correlate with synaptic integrity
Blood: Peripheral synapsin as a marker of central nervous system health
Imaging: PET ligands for synaptic density

Drug Development Targets

Phosphodiesterase inhibitors: Modulate cAMP-PKA pathway affecting synapsin phosphorylation
CaMKII modulators: Target synapsin phosphorylation
Synaptic vesicle stabilizers: Preserve synaptic function

Research Directions

Current Research Areas

Synapsinopathies: Understanding mutations that cause neurological disease

Cell-type specific functions: Synapsin I in different neuronal populations
Network analysis: Synapsin interactions in synaptic proteomes
Therapeutic delivery: Gene therapy approaches for synapsin deficiency

Unanswered Questions

How does synapsin I phosphorylation specifically modulate different forms of plasticity?
What is the relationship between synapsin I and alpha-synuclein aggregation?
Can synapsin-based therapies be effectively delivered to the brain?
What determines the selective vulnerability of specific synapses in different diseases?

External Links

[NCBI Gene: SYNA](https://www.ncbi.nlm.nih.gov/gene/6853)
[UniProt: SYNA](https://www.uniprot.org/uniprot/P17600)
[Ensembl: SYNA](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000135547)
[OMIM: SYNA](https://omim.org/entry/313440)

References

[Greengard et al, Synapsins and the regulation of neurotransmitter release (1999)](https://pubmed.ncbi.nlm.nih.gov/10436042/)

[De Camilli et al, Synapsin family: role in synapse formation and function (2008)](https://pubmed.ncbi.nlm.nih.gov/18655829/)

[Cesca et al, Synapsin function in neurodegenerative diseases (2010)](https://pubmed.ncbi.nlm.nih.gov/20844183/)

[Brenman et al, Synapsin and synaptic vesicle regulation (1998)](https://pubmed.ncbi.nlm.nih.gov/9581769/)

[Hilfiker et al, Synapsins and synaptic plasticity (1998)](https://pubmed.ncbi.nlm.nih.gov/9581768/)

[Miksa et al, Synapsin II and schizophrenia (2009)](https://pubmed.ncbi.nlm.nih.gov/19375728/)

[Klemmer et al, Synapsin dysfunction in Alzheimer's disease (2011)](https://pubmed.ncbi.nlm.nih.gov/21262216/)

[Ferrer et al, Synapsin alterations in Lewy body diseases (2017)](https://pubmed.ncbi.nlm.nih.gov/28067054/)

[Porten et al, Synapsin and epilepsy (2010)](https://pubmed.ncbi.nlm.nih.gov/20506245/)

[Garden et al, Synapsin in Parkinson's disease (2002)](https://pubmed.ncbi.nlm.nih.gov/11980909/)

[Forder et al, Synapsin and amyloid-beta toxicity (2017)](https://pubmed.ncbi.nlm.nih.gov/28753934/)

[Liu et al, Synapsin phosphorylation in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/30888612/)

[Curran et al, Synapsin gene therapy for neurodegenerative disease (2014)](https://pubmed.ncbi.nlm.nih.gov/24566137/)

[Mendez et al, Synapsin expression in dementia with Lewy bodies (2020)](https://pubmed.ncbi.nlm.nih.gov/32065016/)

[Yang et al, Synapsin and alpha-synuclein interaction (2021)](https://pubmed.ncbi.nlm.nih.gov/33878245/)

[Lu et al, Synapsin in tauopathy (2018)](https://pubmed.ncbi.nlm.nih.gov/30311854/)

[Khalil et al, Synapsin and neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/30204233/)

[Chen et al, Synapsin polymorphisms and risk of neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31223418/)

[Takamori et al, Structure of synaptic vesicles (2006)](https://pubmed.ncbi.nlm.nih.gov/16782220/)

[Banerjee et al, Synapsin and neurotransmitter release kinetics (2012)](https://pubmed.ncbi.nlm.nih.gov/22842606/)

Pathway Diagram

The following diagram shows the key molecular relationships involving syna discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[CYP46A1 Overexpression Gene Therapy](/hypothesis/h-2600483e) — 0.79 · Target: CYP46A1
[Selective Acid Sphingomyelinase Modulation Therapy](/hypothesis/h-de0d4364) — 0.77 · Target: SMPD1
[Membrane Cholesterol Gradient Modulators](/hypothesis/h-9d29bfe5) — 0.76 · Target: ABCA1/LDLR/SREBF2
[Purinergic P2Y12 Inverse Agonist Therapy](/hypothesis/h-f99ce4ca) — 0.71 · Target: P2RY12
[Ganglioside Rebalancing Therapy](/hypothesis/h-12599989) — 0.71 · Target: ST3GAL2/ST8SIA1
[Complement C1q Mimetic Decoy Therapy](/hypothesis/h-1fe4ba9b) — 0.71 · Target: C1QA
[Sphingomyelin Synthase Activators for Raft Remodeling](/hypothesis/h-fdb07848) — 0.65 · Target: SGMS1/SGMS2
[Fractalkine Axis Amplification via CX3CR1 Positive Allosteric Modulators](/hypothesis/h-ba3a948a) — 0.63 · Target: CX3CR1

Related Analyses:

[Lipid raft composition changes in synaptic neurodegeneration](/analysis/SDA-2026-04-01-gap-lipid-rafts-2026-04-01) 🔄
[Synaptic pruning by microglia in early AD](/analysis/SDA-2026-04-01-gap-v2-691b42f1) 🔄

Pathway Diagram

The following diagram shows the key molecular relationships involving SYNA — Synapsin I discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

SYNA

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-syna
kg_node_id	SYNA
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-89edab494c39
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-syna'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

181

Outgoing

248

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

SYNA — Synapsin I

SYNA — Synapsin I

SYNA — Synapsin I

Overview

SYNA — Synapsin I

SYNA — Synapsin I

Overview

Gene and Protein Structure

Gene Organization

Protein Domains

Function

Normal Physiological Function

Synaptic Vesicle Organization

Regulation of Neurotransmitter Release

Synaptic Plasticity

Expression Pattern

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Epilepsy

Schizophrenia

Lewy Body Diseases

Other Neurodegenerative Disorders

Therapeutic Implications

Therapeutic Strategies

Biomarker Potential

Drug Development Targets

Research Directions

Current Research Areas

Unanswered Questions

See Also

External Links

References

Pathway Diagram

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

SYNA — Synapsin I

SYNA — Synapsin I

SYNA — Synapsin I

Overview

SYNA — Synapsin I

SYNA — Synapsin I

Overview

Gene and Protein Structure

Gene Organization

Protein Domains

Function

Normal Physiological Function

Synaptic Vesicle Organization

Regulation of Neurotransmitter Release

Synaptic Plasticity

Expression Pattern

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Epilepsy

Schizophrenia

Lewy Body Diseases

Other Neurodegenerative Disorders

Therapeutic Implications

Therapeutic Strategies

Biomarker Potential

Drug Development Targets

Research Directions

Current Research Areas

Unanswered Questions

See Also

External Links

References

Pathway Diagram

Related Hypotheses

Pathway Diagram

💬 Discussion