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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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VAMP1
vesicle associated membrane protein 1
Chromosome 12 Β· 12p13.31
NCBI Gene: 6843Ensembl: ENSG00000139190.17HGNC: HGNC:12642UniProt: F5GZV7
47PubMed Papers
22Diseases
0Drugs
14Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytosolazurophil granule membranespecific granule membranePresynaptic congenital myasthenic syndromesspastic ataxia 1Spastic paraplegiabotulism
✦AI Summary

VAMP1 (vesicle-associated membrane protein 1) is a SNARE complex component that mediates synaptic vesicle fusion and neurotransmitter release at the presynaptic membrane 1. The protein functions by forming complexes with other presynaptic proteins to facilitate the targeting and fusion of transport vesicles to their target membranes, enabling GABA and other neurotransmitter release 2. VAMP1 mutations cause congenital myasthenic syndrome-25 (CMS-25), an autosomal recessive neuromuscular disorder characterized by impaired neuromuscular signal transmission 3. Clinical features of VAMP1-related CMS-25 include muscle weakness, ptosis, feeding difficulties, and motor developmental delay, with emerging evidence of cerebellar involvement and nephrolithiasis in some cases 4. VAMP1 mutations also cause hereditary spastic paraplegia through impaired SNARE complex formation and synaptic vesicle fusion dynamics 5. Additionally, VAMP1 genetic variants associate with BehΓ§et's disease-related uveitis susceptibility 6, and reduced VAMP1 expression in prefrontal cortical interneurons may contribute to schizophrenia pathophysiology by impairing GABAergic inhibition and cortical gamma oscillations 2. Pharmacological interventions including pyridostigmine and salbutamol show variable efficacy in CMS-25 patients 4.

Sources cited
1
VAMP1 mutations cause congenital myasthenic syndromes (CMS-25) by impairing neuromuscular junction function
PMID: 36835142
2
VAMP1 is a SNARE complex component involved in synaptic vesicle exocytosis and neurotransmitter release
PMID: 24534378
3
VAMP1-related CMS-25 presents with muscle weakness, developmental delay, and may include cerebellar hypoplasia and nephrolithiasis
PMID: 38531369
4
VAMP1 mutations impair synaptic vesicle fusion dynamics and cause hereditary spastic paraplegia through altered SNARE complex formation
PMID: 40856587
5
VAMP1 genetic variants associate with susceptibility to BehΓ§et's disease-related uveitis
PMID: 34652073
6
Reduced VAMP1 expression in prefrontal interneurons impairs GABAergic inhibition and cortical gamma power in schizophrenia
PMID: 38273110
Disease Associationsβ“˜22
Presynaptic congenital myasthenic syndromesOpen Targets
0.70Strong
spastic ataxia 1Open Targets
0.70Moderate
Spastic paraplegiaOpen Targets
0.53Moderate
botulismOpen Targets
0.50Moderate
congenital myasthenic syndromeOpen Targets
0.45Moderate
Congenital myasthenic syndromesOpen Targets
0.37Weak
presynaptic congenital myasthenic syndromeOpen Targets
0.37Weak
Houge-Janssens syndrome 2Open Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.23Weak
genetic disorderOpen Targets
0.17Weak
Alzheimer diseaseOpen Targets
0.08Suggestive
schizophreniaOpen Targets
0.06Suggestive
dystonia 31Open Targets
0.04Suggestive
Progressive supranuclear palsy - pure akinesia with gait freezingOpen Targets
0.03Suggestive
progressive supranuclear palsy-pure akinesia with gait freezing syndromeOpen Targets
0.03Suggestive
Hereditary late-onset Parkinson diseaseOpen Targets
0.03Suggestive
Young adult-onset ParkinsonismOpen Targets
0.03Suggestive
spinocerebellar ataxia type 27Open Targets
0.03Suggestive
Autosomal dominant striatal neurodegenerationOpen Targets
0.03Suggestive
autosomal dominant striatal neurodegeneration type 1Open Targets
0.03Suggestive
Myasthenic syndrome, congenital, 25, presynapticUniProt
Spastic ataxia 1, autosomal dominantUniProt
Pathogenic Variants14
NM_014231.5(VAMP1):c.340+2T>GPathogenic
Spastic ataxia 1|Spastic paraplegia|not provided|Spastic ataxia 1;Myasthenic syndrome, congenital, 25, presynaptic
β˜…β˜…β˜†β˜†2025
NM_014231.5(VAMP1):c.97C>T (p.Arg33Ter)Pathogenic
Spastic paraplegia|Spastic ataxia 1
β˜…β˜…β˜†β˜†2025β†’ Residue 33
NM_014231.5(VAMP1):c.340del (p.Ile114fs)Pathogenic
Myasthenic syndrome, congenital, 25, presynaptic|not provided|Spastic paraplegia|Spastic ataxia 1|VAMP1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 114
NM_014231.5(VAMP1):c.340+2T>APathogenic
not provided|Spastic paraplegia
β˜…β˜…β˜†β˜†2022
NM_014231.5(VAMP1):c.129+2T>GLikely pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2025
NM_014231.5(VAMP1):c.118C>T (p.Gln40Ter)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2025β†’ Residue 40
NM_014231.5(VAMP1):c.129+1G>ALikely pathogenic
Myasthenic syndrome, congenital, 25, presynaptic|Houge-Janssens syndrome 2
β˜…β˜†β˜†β˜†2025
NM_014231.5(VAMP1):c.59del (p.Gly20fs)Pathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2023β†’ Residue 20
NC_000012.12:g.(?_6462812)_(6470551_?)delPathogenic
Spastic paraplegia
β˜…β˜†β˜†β˜†2019
NM_014231.5(VAMP1):c.230C>A (p.Ser77Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 77
NM_014231.5(VAMP1):c.152dup (p.Asn51fs)Likely pathogenic
Spastic ataxia 1
β˜…β˜†β˜†β˜†β†’ Residue 51
NM_014231.5(VAMP1):c.341-24G>ALikely pathogenic
Myasthenic syndrome, congenital, 25, presynaptic
β˜†β˜†β˜†β˜†2022
NM_014231.5(VAMP1):c.51_64del (p.Gly18fs)Pathogenic
Myasthenic syndrome, congenital, 25, presynaptic
β˜†β˜†β˜†β˜†2019β†’ Residue 18
NM_014231.5(VAMP1):c.128_129del (p.Glu43fs)Pathogenic
Myasthenic syndrome, congenital, 25, presynaptic
β˜†β˜†β˜†β˜†2019β†’ Residue 43
View on ClinVar β†—
Related Genes
SNAP23Protein interaction100%STX6Protein interaction100%VTI1AProtein interaction100%VAMP7Protein interaction100%STX16Protein interaction100%STX1BProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
64%
Liver
19%
Lung
17%
Ovary
15%
Heart
11%
Gene Interaction Network
Click a node to explore
VAMP1SNAP23STX6VTI1AVAMP7STX16STX1B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P23763
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.28LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.81 [0.52–1.28]
RankingsWhere VAMP1 stands among ~20K protein-coding genes
  • #9,286of 20,598
    Most Researched47
  • #2,532of 5,498
    Most Pathogenic Variants14
  • #13,506of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedVAMP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
PMID: 36835142
Int J Mol Sci Β· 2023
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet Β· 2017
0.80
4
VAMP1-Related Congenital Myasthenic Syndrome: A Case Report and Literature Review.
PMID: 38531369
Neuropediatrics Β· 2024
0.70
5
The Impact of VAMP1 Mutations on Synaptic Vesicle Fusion Dynamics in Familial Spastic Disorders.
PMID: 40856587
J Child Neurol Β· 2026
0.60