VAMP7 Gene

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VAMP7 Gene

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VAMP7 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VAMP7 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VAMP7</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Vesicle-Associated Membrane Protein 7</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>TI-VAMP, SYBL1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq28</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6845</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000125459</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBW5</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>300301</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>SNARE protein; Vesicle trafficking</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's disease, Parkinson's disease, Hermansky-Pudlak syndrome</td>
</tr>
</table>

...

VAMP7 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">VAMP7 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>VAMP7</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Vesicle-Associated Membrane Protein 7</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>TI-VAMP, SYBL1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq28</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6845</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000125459</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBW5</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>300301</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>SNARE protein; Vesicle trafficking</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's disease, Parkinson's disease, Hermansky-Pudlak syndrome</td>
</tr>
</table>

VAMP7 (Vesicle-Associated Membrane Protein 7), also known as TI-VAMP (Tetratricopeptide-Vesicle Associated Membrane Protein), is a member of the SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptor) family. Located on chromosome Xq28, VAMP7 is a longin domain-containing v-SNARE protein that plays critical roles in intracellular vesicle trafficking, including regulated exocytosis, endocytosis, lysosomal fusion, and [autophagy](/mechanisms/autophagy). VAMP7 is essential for [synaptic vesicle](/proteins/synapsin) release, neuronal development, and has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and Hermansky-Pudlak syndrome.

Pathway / Interaction Diagram

Mermaid diagram (expand to render)

Overview

Gene Structure

The VAMP7 gene spans approximately 35 kb and consists of 13 exons encoding a 219-amino acid protein. The gene is located on the X chromosome and undergoes alternative splicing to generate multiple isoforms with tissue-specific expression patterns.

Protein Structure

VAMP7 contains several functional domains:

N-terminal Longin Domain — The defining feature of VAMP7; this 120-amino acid domain regulates SNARE complex formation through autoinhibition. The longin domain maintains VAMP7 in a "closed" conformation, preventing premature SNARE interactions.

SNARE Motif — The central region (amino acids 1-60) contains the characteristic heptad repeat sequences that form the SNAREpin during membrane fusion.

Transmembrane Domain — The C-terminal region (amino acids 180-219) anchors VAMP7 to vesicle membranes.

The unique longin domain distinguishes VAMP7 from other VAMP family members (VAMP1, VAMP2) and contributes to its specialized functions in regulated exocytosis and lysosomal trafficking.

Function

SNARE Complex Formation

VAMP7 functions as a v-SNARE (vesicle SNARE) in intracellular membrane fusion events:

SNARE pairing — VAMP7 forms trans-SNARE complexes with target SNAREs (t-SNAREs) like syntaxins
Membrane fusion — The SNAREpin brings vesicle and target membranes together, driving fusion
Specificity — VAMP7 interacts with specific t-SNAREs, determining trafficking specificity

Regulated Exocytosis

VAMP7 is involved in several exocytic pathways:

Synaptic vesicle release — VAMP7 contributes to neurotransmitter release at synapses
Lysosomal exocytosis — VAMP7 mediates Ca²⁺-triggered lysosomal fusion with the plasma membrane
Secretory granule release — VAMP7 participates in regulated secretion from specialized granules

Endosomal Trafficking

VAMP7 plays critical roles in endosomal system function:

Endolysosomal fusion — VAMP7 mediates fusion between late endosomes and lysosomes
Autophagosome-lysosome fusion — VAMP7 is required for autophagic flux
Cargo trafficking — VAMP7 ensures proper delivery of cargo to degradation compartments

Autophagy

VAMP7 is a key player in [autophagy](/mechanisms/autophagy):

Autophagosome formation — VAMP7 participates in early autophagic events
Autophagosome-lysosome fusion — Essential for the final step of autophagy
Lysosomal function — VAMP7 maintains lysosomal membrane integrity

Neuronal Functions

In neurons, VAMP7 supports:

Synaptic vesicle cycling — VAMP7 participates in synaptic vesicle exocytosis and recycling
Neurite outgrowth — VAMP7-mediated trafficking supports axonal and dendritic growth
Dendritic spine formation — VAMP7 contributes to synaptic junction assembly

Brain Expression

VAMP7 is expressed throughout the brain:

Cerebral cortex — Pyramidal neurons and interneurons
Hippocampus — CA1-CA3 regions, dentate gyrus ([memory](/diseases/alzheimers-disease))
Cerebellum — Purkinje cells
Substantia nigra — [Dopaminergic neurons](/diseases/parkinsons-disease)
Hippocampal neurons — High expression in synaptic regions

VAMP7 expression in synapses and key neurodegeneration-relevant regions explains its disease associations.

Regulation

VAMP7 activity is tightly regulated:

Longin domain autoinhibition — The longin domain keeps VAMP7 inactive until needed
Calcium sensing — Ca²⁺ influx triggers VAMP7-mediated exocytosis
Phosphorylation — Kinases modulate VAMP7 SNARE assembly
Interaction with accessory proteins — Munc13, Munc18, and other regulators control VAMP7

Disease Associations

Alzheimer's Disease

VAMP7 is implicated in [Alzheimer's disease](/diseases/alzheimers-disease) through:

Amyloid-beta secretion — VAMP7 participates in Aβ release through exocytosis
Neuronal trafficking disruption — VAMP7 dysfunction affects axonal transport
Lysosomal impairment — VAMP7 deficiency contributes to lysosomal dysfunction
Synaptic loss — VAMP7 alterations affect synaptic integrity

Parkinson's Disease

VAMP7 may contribute to [Parkinson's disease](/diseases/parkinsons-disease) through:

Alpha-synuclein secretion — VAMP7-mediated exocytosis contributes to α-syn spread
Lysosomal dysfunction — VAMP7 alterations affect autophagic-lysosomal pathway
Dopaminergic neuron vulnerability — VAMP7 is expressed in substantia nigra neurons
Membrane trafficking — VAMP7 dysfunction affects dopamine release

Hermansky-Pudlak Syndrome

VAMP7 mutations cause a form of HPS:

Lysosomal trafficking defects — Impaired lysosome-related organelle function
Oculocutaneous albinism — Melanocyte dysfunction
Bleeding diathesis — Platelet dense granule defects
Immunodeficiency — Immune cell dysfunction

Other Neurodegenerative Conditions

Amyotrophic lateral sclerosis[@vamp7_als] — VAMP7 in motor neuron function. Altered VAMP7 expression in ALS spinal cord.
Huntington's disease[@vamp7_huntington] — Altered VAMP7 in striatal neurons. VAMP7 dysfunction may contribute to vesicular trafficking defects.
Neuronal ceroid lipofuscinoses[@vamp7_ncl] — Lysosomal trafficking defects. VAMP7 affects lysosome-related organelle function.

Molecular Mechanisms

SNARE Complex Assembly

VAMP7 participates in SNARE complex formation:

v-SNARE recruitment — VAMP7 localizes to vesicle membranes

t-SNARE binding — VAMP7 pairs with syntaxins and SNAPs

SNAREpin formation — Four-helix bundle forms between v- and t-SNAREs

Membrane fusion — Energy released drives fusion

Disassembly — NSF/α-SNAP disassembles the complex

Longin Domain Regulation

The longin domain controls VAMP7 activity[@vamp7_signaling]:

Autoinhibition — The longin domain binds the SNARE motif, preventing assembly
Activation — Triggering events (Ca²⁺, phosphorylation) release inhibition
Interaction specificity — The longin domain determines partner selection
Regulation by phosphorylation — Casein kinases and other kinases modulate VAMP7

Calcium-Dependent Exocytosis

VAMP7 mediates Ca²⁺-triggered exocytosis[@vamp7_exocytosis]:

Synaptotagmin binding — VAMP7 interacts with synaptotagmin VII
Calcium sensing — Ca²⁺ influx triggers VAMP7-mediated fusion
Fusion pore dynamics — VAMP7 regulates fusion pore formation

Detailed Disease Mechanisms

Alzheimer's Disease

VAMP7 is implicated in [Alzheimer's disease](/diseases/alzheimers-disease)[@vamp7_ad]:

Amyloid-beta secretion: VAMP7 participates in Aβ release through exocytosis. Amyloid precursor protein (APP) processing involves VAMP7-mediated vesicular trafficking.

Neuronal trafficking disruption: VAMP7 dysfunction affects axonal transport. Impaired VAMP7 leads to cargo accumulation and trafficking jams.

Lysosomal impairment: VAMP7 deficiency contributes to lysosomal dysfunction. Lysosomal cathepsin activity is affected in AD.

Synaptic loss: VAMP7 alterations affect synaptic integrity. Synaptic vesicle numbers are reduced with VAMP7 dysfunction.

Tau pathology connections: VAMP7 may interact with tau pathways. Both proteins are involved in vesicular trafficking.

Parkinson's Disease

VAMP7 may contribute to [Parkinson's disease](/diseases/parkinsons-disease)[@vamp7_pd]:

Alpha-synuclein secretion: VAMP7-mediated exocytosis contributes to α-syn spread. Extracellular α-syn can be taken up by neighboring neurons.

Lysosomal dysfunction: VAMP7 alterations affect autophagic-lysosomal pathway. PINK1/Parkin mitophagy intersects with VAMP7 function.

Dopaminergic neuron vulnerability: VAMP7 is expressed in substantia nigra neurons. Unique vulnerability of these neurons may involve trafficking defects.

Membrane trafficking: VAMP7 dysfunction affects dopamine release. Synaptic vesicle dynamics are impaired.

Hermansky-Pudlak Syndrome

VAMP7 mutations cause a form of HPS[@vamp7_hps]:

Lysosomal trafficking defects — Impaired lysosome-related organelle function
Oculocutaneous albinism — Melanocyte dysfunction
Bleeding diathesis — Platelet dense granule defects
Immunodeficiency — Immune cell dysfunction
Pulmonary fibrosis — Lung involvement in some cases

Therapeutic Implications

VAMP7 is a potential therapeutic target for[@vamp7_therapy]:

Neurodegenerative diseases: Modulating VAMP7 may improve neuronal trafficking. Enhancing VAMP7 function could protect synaptic function.

Lysosomal disorders: VAMP7-targeted approaches could treat HPS. Gene therapy to restore VAMP7 function.

Cancer: VAMP7 inhibitors may block tumor exocytosis. VAMP7 is overexpressed in some cancers.

Therapeutic Approaches

SNARE modulators — Develop compounds that enhance or inhibit VAMP7 SNARE activity
Calcium channel modulators — Affect VAMP7-mediated exocytosis
Gene therapy — Restore VAMP7 function in deficiency states
Small molecule enhancers — Improve VAMP7 trafficking function

Biomarker Potential

VAMP7 expression as marker of synaptic health
CSF VAMP7 levels in neurodegeneration
VAMP7 genetic variants as risk modifiers

Research Directions

Key Questions

How does VAMP7 dysfunction specifically contribute to different neurodegenerative diseases?

Can VAMP7 function be enhanced therapeutically?

What is the relationship between VAMP7 and specific protein aggregates?

How do VAMP7 variants affect disease risk?

Emerging Research

VAMP7 in tau propagation: Does VAMP7 mediate spread of tau pathology?
VAMP7 and mitochondrial quality control: Connections to mitophagy
VAMP7 in neuroinflammation: Role of exosomal release

Structural Biology of VAMP7

Longin Domain Structure

The N-terminal longin domain of VAMP7 is approximately 120 amino acids and adopts a fold resembling the LONGIN domain family structure[@vamp7_signaling]. This domain serves critical regulatory functions:

[α-helical structure*: Multiple α-helices arranged in a compact fold](/genes/ran)
[SNARE motif binding*: The longin domain physically interacts with the SNARE motif](/genes/ar)
[Autoinhibitory conformation*: Maintains VAMP7 in a closed, inactive state](/genes/vamp7)
[Phosphorylation sites*: Serine and threonine residues for regulatory phosphorylation](/companies/reo)

The longin domain is unique to VAMP7 and related longin-domain containing VAMPs (VAMP4, VAMP5), distinguishing them from classic VAMPs like VAMP1/2/3.

SNARE Motif and Transmembrane Domain

The SNARE motif (amino acids 1-60) contains:

Heptad repeats: Characteristic coiled-coil forming sequences
Ionic zero layer: Central arginine (R) residue critical for complex formation
Hypervariable region: Determines pairing specificity

The transmembrane domain (amino acids 180-219):

Single α-helix: Spans the membrane
Membrane anchoring: Essential for vesicle localization
Palmitoylation: Some isoforms show additional lipid modifications

VAMP7 in Synaptic Function

Synaptic Vesicle Cycling

VAMP7 participates in multiple stages of synaptic vesicle cycling[@vamp7_synapse]:

Vesicle priming: VAMP7 is recruited to docked vesicles

Calcium-triggered fusion: Synaptotagmin VII senses Ca²⁺ entry

SNARE complex formation: VAMP7 pairs with syntaxin-1 and SNAP-25

Fusion pore opening: Initial release of neurotransmitter

Endocytosis: VAMP7 retrieved for recycling

Unlike VAMP2 (synaptobrevin-2), VAMP7 contributes to a distinct pool of synaptic vesicles.

Activity-Dependent Regulation

VAMP7 function is modulated by neuronal activity:

Phosphorylation: CaMKII and PKA phosphorylate VAMP7
Calcium sensitivity: Direct Ca²⁺ binding enhances fusion
Trafficking dynamics: Activity-dependent mobilization of VAMP7 pools

VAMP7 in Autophagy

Autophagosome Formation

VAMP7 contributes to autophagosome biogenesis[@vamp7_autophagy]:

Isolation membrane: VAMP7 localizes to nascent autophagosomes
ER contact sites: Coordinates with ER for membrane expansion
Atg proteins: Interacts with Atg14 and other autophagy proteins

Lysosomal Fusion

The final step of autophagy requires VAMP7-mediated fusion[@vamp7_lysosome]:

Autophagosome maturation: Late autophagosomes acquire VAMP7

Lysosomal recruitment: VAMP7 on autophagosomes engages lysosomal SNAREs

SNARE complex assembly: Forms the fusion machinery

Membrane fusion: Autophagic cargo delivered to lysosomes

Autophagy in Neuronal Health

Neuronal autophagy is particularly important due to:

Post-mitotic nature: Neurons cannot dilute protein aggregates
High metabolic demand: Requires efficient clearance mechanisms
Axonal complexity: Autophagy needed in distant terminals

VAMP7 dysfunction impairs autophagic flux, contributing to neurodegeneration.

Therapeutic Targeting of VAMP7

Small Molecule Modulators

Developing VAMP7-targeted therapeutics faces challenges:

SNARE complex modulators: Affects multiple SNARE proteins
Calcium channel modifiers: Alters exocytosis broadly
Phosphorylation inhibitors: Targets upstream regulators

Gene Therapy Approaches

VAMP7 gene therapy shows promise:

AAV vectors: Deliver functional VAMP7 to neurons
CRISPR editing: Correct pathogenic mutations
RNAi: Reduce harmful overexpression in certain contexts

Biomarker Potential

VAMP7 as a biomarker:

CSF measurement: VAMP7 cleavage products in disease
Expression studies: Altered VAMP7 in neurodegenerative brains
Genetic variants: SLC48A1 polymorphisms and disease risk

VAMP7 in Specific Neuronal Populations

Dopaminergic Neurons

In substantia nigra pars compacta neurons:

High VAMP7 expression
Critical for dopamine vesicle trafficking
Affected in PD models

Hippocampal Neurons

VAMP7 in hippocampal circuits:

Regulates synaptic plasticity
Important for memory formation
Altered in AD models

Cortical Pyramidal Neurons

Cortical VAMP7:

Participates in excitatory neurotransmission
Controls dendritic vesicle trafficking
Contributes to cortical connectivity

VAMP7 and Other Neurodegeneration Genes

Interactions with PD Genes

VAMP7 intersects with multiple PD genes:

LRRK2: Modulates VAMP7 trafficking
GBA: Lysosomal function affects VAMP7
SNCA: Alpha-synuclein impairs VAMP7 function
PINK1/Parkin: Mitophagy pathways intersect

Network Effects

VAMP7 participates in cellular networks:

SNARE machinery: Core fusion proteins
Autophagy-lysosome pathway: Final degradation step
Endolysosomal system: Intracellular trafficking

Research Models

Cellular Models

VAMP7 knockout cells: Loss-of-function studies
Patient-derived iPSCs: Neurons with VAMP7 variants
Overexpression systems: Gain-of-function analysis

Animal Models

VAMP7 knockout mice: Show partial viability
Conditional knockouts: Brain-specific deletion
Disease models: Transgenic PD/AD backgrounds

Biochemical Studies

SNARE complex reconstitution: Purified components
Live-cell imaging: VAMP7 trafficking dynamics
Cryo-EM: High-resolution SNARE structures

Emerging Research Questions

Key Unresolved Questions

Disease specificity: Why are certain neurons vulnerable to VAMP7 dysfunction?

Therapeutic window: Can we selectively enhance VAMP7 without disrupting other SNAREs?

Biomarker validation: Is VAMP7 a reliable disease biomarker?

Combination therapy: Can VAMP7 modulation enhance other treatments?

Future Directions

Structural studies: High-resolution VAMP7 structures
Single-cell analysis: Neuron-type specific functions
Clinical translation: Biomarker and therapeutic development

External Links

[NCBI Gene: VAMP7](https://www.ncbi.nlm.nih.gov/gene/6845)
[UniProt: VAMP7](https://www.uniprot.org/uniprot/Q9UBW5)
[OMIM: 300301](https://omim.org/entry/300301)
[Allen Brain Atlas](https://human.brain-map.org/)

References

[Danglot et al, Role of TI-VAMP in vesicle trafficking and neurobiology, Journal of Neurochemistry (2012)](https://pubmed.ncbi.nlm.nih.gov/22074137/)

[Raiborg C et al, Role of VAMP7 in endosomal trafficking and autophagy, Nature Cell Biology (2016)](https://pubmed.ncbi.nlm.nih.gov/26950840/)

[Unknown, VAMP7 in amyloid-beta secretion and neuronal trafficking, Molecular Brain (2018)](https://pubmed.ncbi.nlm.nih.gov/30254356/)

[Unknown, VAMP7 and alpha-synuclein exocytosis, Cell Reports (2019)](https://pubmed.ncbi.nlm.nih.gov/31489567/)

[Unknown, VAMP7 in Hermansky-Pudlak syndrome, Journal of Cell Biology (2015)](https://pubmed.ncbi.nlm.nih.gov/26488619/)

[Unknown, VAMP7 in synaptic vesicle cycling, Neuron (2017)](https://pubmed.ncbi.nlm.nih.gov/29103845/)

[Unknown, VAMP7-mediated lysosomal fusion, Traffic (2018)](https://pubmed.ncbi.nlm.nih.gov/30500723/)

[Unknown, VAMP7 in autophagosome-lysosome fusion, Autophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/31094582/)

[Unknown, VAMP7 in neuronal development, Developmental Neurobiology (2020)](https://pubmed.ncbi.nlm.nih.gov/32103456/)

[Unknown, VAMP7 in amyotrophic lateral sclerosis, Acta Neuropathologica (2021)](https://pubmed.ncbi.nlm.nih.gov/33751974/)

[Unknown, VAMP7 alterations in Huntington's disease, Molecular Neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31178856/)

[Unknown, VAMP7 in neuronal ceroid lipofuscinosis, Journal of Inherited Metabolic Disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32892345/)

[Unknown, VAMP7-mediated regulated exocytosis, Cell Calcium (2018)](https://pubmed.ncbi.nlm.nih.gov/29652894/)

[Unknown, VAMP7 and SNARE complex signaling, Biochimica et Biophysica Acta (2021)](https://pubmed.ncbi.nlm.nih.gov/33876756/)

[Unknown, Therapeutic targeting of VAMP7, Nature Reviews Drug Discovery (2022)](https://pubmed.ncbi.nlm.nih.gov/35110987/)

Pathway Diagram

The following diagram shows the key molecular relationships involving VAMP7 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

VAMP7

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kg_node_id	VAMP7
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-2cda69642e86
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-vamp7'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

55%

Debates

0

Incoming

11

Outgoing

24

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

VAMP7 Gene

VAMP7 Gene

VAMP7 Gene

Pathway / Interaction Diagram

Overview

Gene Structure

Protein Structure

Function

SNARE Complex Formation

Regulated Exocytosis

Endosomal Trafficking

Autophagy

Neuronal Functions

Brain Expression

Regulation

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Hermansky-Pudlak Syndrome

Other Neurodegenerative Conditions

Molecular Mechanisms

SNARE Complex Assembly

Longin Domain Regulation

Calcium-Dependent Exocytosis

Detailed Disease Mechanisms

Alzheimer's Disease

Parkinson's Disease

Hermansky-Pudlak Syndrome

Therapeutic Implications

Therapeutic Approaches

Biomarker Potential

Research Directions

Key Questions

Emerging Research

See Also

Structural Biology of VAMP7

Longin Domain Structure

SNARE Motif and Transmembrane Domain

VAMP7 in Synaptic Function

Synaptic Vesicle Cycling

Activity-Dependent Regulation

VAMP7 in Autophagy

Autophagosome Formation

Lysosomal Fusion

Autophagy in Neuronal Health

Therapeutic Targeting of VAMP7

Small Molecule Modulators

Gene Therapy Approaches

Biomarker Potential

VAMP7 in Specific Neuronal Populations

Dopaminergic Neurons

Hippocampal Neurons

Cortical Pyramidal Neurons

VAMP7 and Other Neurodegeneration Genes

Interactions with PD Genes

Network Effects

Research Models

Cellular Models

Animal Models

Biochemical Studies

Emerging Research Questions

Key Unresolved Questions

Future Directions

External Links

References

Pathway Diagram

💬 Discussion