Details for: VAMP1

Gene ID: 6843

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: VAMP1

Ensembl ID: ENSG00000139190

Description: vesicle associated membrane protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal ganglion cell CL0000740
    CSI 5.25
    rCSI 11.59%
    PRS 89.71
  • double negative thymocyte CL0002489
    CSI 4.14
    rCSI 2.88%
    PRS 99.09
  • rod bipolar cell CL0000751
    CSI 3.07
    rCSI 5.52%
    PRS 92.92
  • ON-bipolar cell CL0000749
    CSI 3.01
    rCSI 4.48%
    PRS 94.72
  • cerebral cortex neuron CL0010012
    CSI 2.52
    rCSI 10.26%
    PRS 90.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.84
    rCSI 2.29%
    PRS 87.26
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.79
    rCSI 3.05%
    PRS 98.27
  • inhibitory interneuron CL0000498
    CSI 1.64
    rCSI 3.78%
    PRS 90.59
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.48
    rCSI 4.63%
    PRS 90.95
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.29
    rCSI 2.16%
    PRS 89.02
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.94
    rCSI 2.27%
    PRS 87.27
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.64
    rCSI 2.3%
    PRS 87.43

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Vesicle-associated membrane protein 1, encoded by the [VAMP1](/details-gene/6843) gene, is a key component of the SNARE complex machinery essential for vesicle fusion. Its function is critical for processes requiring rapid exocytosis, such as neurotransmitter release at synaptic terminals. This is reflected in its high significance as an expression marker in various neuronal populations, including [retinal ganglion cells](/details-cell/CL0000740) and [cerebral cortex neurons](/details-cell/CL0010012). Interestingly, its prominent expression in immune cells like [double negative thymocytes](/details-cell/CL0002489) and [activated CD8-positive, alpha-beta T cells](/details-cell/CL0001049) suggests a parallel role in immune cell trafficking and effector functions. Mutations in [VAMP1](/details-gene/6843) are linked to severe neurological disorders, including hereditary spastic ataxia ([185880](https://omim.org/entry/185880)) and congenital myasthenic syndromes ([108600](https://omim.org/entry/108600)), highlighting its indispensable role in neuromuscular function. ## Cellular Roles and Expression Landscape The expression profile of [VAMP1](/details-gene/6843) underscores its fundamental role in specialized secretory cells, particularly within the nervous and immune systems. **Overall**, the gene's significance is highest in neuronal subtypes, establishing it as a core component of the neural exocytotic machinery. It is a top marker in cells of the retina, such as the [retinal ganglion cell](/details-cell/CL0000740), [rod bipolar cell](/details-cell/CL0000751), and [ON-bipolar cell](/details-cell/CL0000749). Its importance extends to the central nervous system, with high CSI scores in various [cerebral cortex neurons](/details-cell/CL0010012), including specific inhibitory interneurons like [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) and glutamatergic projection neurons. This widespread neuronal expression is consistent with its canonical function in mediating the fusion of synaptic vesicles with the presynaptic membrane. Beyond the nervous system, [VAMP1](/details-gene/6843) shows notable significance in specific immune cell populations. It is highly ranked in [double negative thymocytes](/details-cell/CL0002489), an early stage of T cell development, suggesting a potential role in thymic selection or differentiation processes that may involve regulated secretion. Furthermore, its expression in [activated CD8-positive, alpha-beta T cells](/details-cell/CL0001049) points towards a function in cytotoxic T lymphocyte activity, likely participating in the SNARE-mediated release of cytotoxic granules to eliminate target cells. ## Pathways and Molecular Function Functionally, [VAMP1](/details-gene/6843) acts as a v-SNARE (vesicle SNARE) protein. Its primary molecular function is [SNARE complex assembly](/details-go/GO:0035493) and possessing [SNARE receptor activity](/details-go/GO:0005484), which involves binding to t-SNAREs (target SNAREs) like syntaxin ([GO:0019905](https://www.ebi.ac.uk/QuickGO/term/GO:0019905)) on the target membrane to drive [vesicle fusion](/details-go/GO:0006906). Cellular component annotations place [VAMP1](/details-gene/6843) on the membranes of various secretory vesicles. It is a canonical component of the [synaptic vesicle membrane](/details-go/GO:0030672), consistent with its role in neurotransmission. Its localization to the [azurophil granule membrane](/details-go/GO:0035577), [specific granule membrane](/details-go/GO:0035579), and [tertiary granule membrane](/details-go/GO:0070821) in immune cells provides a direct mechanistic link to its potential role in the degranulation of neutrophils and cytotoxic T cells. One study also identified a splice isoform containing a mitochondrial targeting signal, suggesting a distinct function at the [mitochondrial outer membrane](/details-go/GO:0005741) ([Link](https://doi.org/10.1091/mbc.9.7.1649)). The Reactome pathway data highlights its role in pathology, specifically as a target for bacterial toxins. [VAMP1](/details-gene/6843) is cleaved by clostridial neurotoxins, such as botulinum toxins, as detailed in the '[Neurotoxicity of clostridium toxins](/details-reactome/R-HSA-168799)' pathway. This proteolytic cleavage prevents SNARE complex formation, blocks neurotransmitter release, and causes paralysis, a mechanism exploited both in disease and for therapeutic applications ([Link](https://doi.org/10.1111/j.1348-0421.2012.00434.x)). ## Research Directions The dual-specialization of [VAMP1](/details-gene/6843) in both neuronal and immune exocytosis provides fertile ground for future investigation. While its role in the synapse is well-established, its specific functions in immunology are less defined. ### Proposed Hypotheses: 1. **Hypothesis:** The high significance of [VAMP1](/details-gene/6843) in [activated CD8-positive, alpha-beta T cells](/details-cell/CL0001049) indicates that it is a primary v-SNARE mediating the targeted release of cytotoxic granules (containing perforin and granzymes), and its knockdown would specifically impair target cell killing without affecting T-cell activation or cytokine secretion. 2. **Hypothesis:** The expression of [VAMP1](/details-gene/6843) in [double negative thymocytes](/details-cell/CL0002489) is required for a specific secretory event during T-cell development, possibly the release of autocrine or paracrine signals necessary to pass a developmental checkpoint, such as beta-selection. ### Key Experimental Approach: To test the first hypothesis regarding the role of [VAMP1](/details-gene/6843) in cytotoxic T lymphocyte (CTL) function, a targeted genetic approach could be employed. * **Experiment:** Generate a conditional knockout of [VAMP1](/details-gene/6843) in the T-cell lineage of a mouse model (e.g., using a *Cd4-Cre* driver). Isolate CD8+ T cells from these mice and control littermates, activate them *in vitro* to differentiate them into CTLs, and co-culture them with fluorescently-labeled target cells (e.g., peptide-pulsed tumor cells). * **Analysis:** Target cell killing can be quantified using flow cytometry-based cytotoxicity assays. CTL degranulation can be measured by monitoring the surface expression of CD107a (LAMP1). A significant reduction in target cell lysis and CD107a externalization in the [VAMP1](/details-gene/6843)-deficient CTLs compared to controls would validate its critical role in CTL effector function. ### Therapeutic Potential: Given that [VAMP1](/details-gene/6843) is a fundamental component of vesicle fusion in critical cell types, it is a challenging therapeutic target. Both gain-of-function and loss-of-function mutations are associated with severe inherited neurological diseases, indicating that its activity is tightly regulated and that systemic inhibition would likely lead to unacceptable toxicity, particularly in the central nervous system ([Link](https://doi.org/10.1016/j.ajhg.2012.07.018); [Link](https://doi.org/10.1002/ana.24905)). Therefore, direct modulation of [VAMP1](/details-gene/6843) activity is unlikely to be a viable therapeutic strategy. Instead, its primary clinical relevance lies in its utility as a diagnostic marker for related congenital myasthenic syndromes and as the well-established target of botulinum neurotoxins, which are themselves used therapeutically to induce localized paralysis.

Genular Protein ID: 3772015989

Symbol: VAMP1_HUMAN

Name: Vesicle-associated membrane protein 1

UniProtKB Accession Codes:

P23763 A8MVP3 D3DUR3 O75468 Q15857 Q6FG94 Q8IVC9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 15 Ensembl 3 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 2 PIRSF 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 3 RefSeq 4 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1976629

Title: Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2.

PubMed ID: 1976629

DOI: 10.1016/s0021-9258(17)44898-8

PubMed ID: 9658161

Title: A splice-isoform of vesicle-associated membrane protein-1 (VAMP-1) contains a mitochondrial targeting signal.

PubMed ID: 9658161

DOI: 10.1091/mbc.9.7.1649

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22958904

Title: VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.

PubMed ID: 22958904

DOI: 10.1016/j.ajhg.2012.07.018

PubMed ID: 22289120

Title: Specificity of botulinum protease for human VAMP family proteins.

PubMed ID: 22289120

DOI: 10.1111/j.1348-0421.2012.00434.x

PubMed ID: 28168212

Title: Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome.

PubMed ID: 28168212

DOI: 10.1002/acn3.387

PubMed ID: 28253535

Title: Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.

PubMed ID: 28253535

DOI: 10.1002/ana.24905

PubMed ID: 28600779

Title: The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.

PubMed ID: 28600779

DOI: 10.1007/s00439-017-1821-8

PubMed ID: 29540745

Title: Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity.

PubMed ID: 29540745

DOI: 10.1038/s41598-018-22842-4

Sequence Information:

  • Length: 118
  • Mass: 12902
  • Checksum: 64CE9615447B686B
  • Sequence:
    • MSAPAQPPAE GTEGTAPGGG PPGPPPNMTS NRRLQQTQAQ VEEVVDIIRV NVDKVLERDQ 
KLSELDDRAD ALQAGASQFE SSAAKLKRKY WWKNCKMMIM LGAICAIIVV VIVIYFFT

Genular Protein ID: 3302157323

Symbol: F5GZV7_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5GZV7

Database IDs:

ARBA 4 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRINTS 1 PROSITE 3 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 2 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

Sequence Information:

  • Length: 116
  • Mass: 12600
  • Checksum: 97AA002B686B1AE6
  • Sequence:
    • MSAPAQPPAE GTEGTAPGGG PPGPPPNMTS NRRLQQTQAQ VEEVVDIIRV NVDKVLERDQ 
KLSELDDRAD ALQAGASQFE SSAAKLKRKY WWKNCKMMIM LGAICAIIVV VIVRRG