VAMP1

Chr 12ARAD

vesicle associated membrane protein 1

Also known as: CMS25, SAX1, SPAX1, SYB1, VAMP-1

NCBI Gene: 6843ENSG00000139190UniProt: P23763

Synapotobrevins, syntaxins, and the synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 25MIM #618323
AR
Spastic ataxia 1, autosomal dominantMIM #108600
AD
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VAMP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.15LOEUF
pLI 0.004
Z-score 1.28
OE 0.54 (0.28–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.23Z-score
OE missense 0.57 (0.44–0.75)
38 obs / 66.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.54 (0.28–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.44–0.75)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 5 / 9.2Missense obs/exp: 38 / 66.3Syn Z: 0.47

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

VAMP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myasthenic syndrome, congenital, 25

MIM #618323

Molecular basis of disorder known

Autosomal recessive

Spastic ataxia 1, autosomal dominant

MIM #108600

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D et al.·Hum Genet
2017
VAMP1-Related Congenital Myasthenic Syndrome: A Case Report and Literature Review.
Yıldırım M et al.·Neuropediatrics
2024Review
The Impact of VAMP1 Mutations on Synaptic Vesicle Fusion Dynamics in Familial Spastic Disorders.
Israr S et al.·J Child Neurol
2026Review
Recessive VAMP1 mutations associated with severe congenital myasthenic syndromes - A recognizable clinical phenotype.
Polavarapu K et al.·Eur J Paediatr Neurol
2021Case report
Identification and validation of prognostic biomarkers in ccRCC: immune-stromal score and survival prediction.
Lyu F et al.·BMC Cancer
2025
Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals.
Cotrina-Vinagre FJ et al.·J Hum Genet
2024Case report
Identification of a novel Vamp1 splice variant in the cochlear nucleus.
Friedland DR et al.·Hear Res
2008
VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families.
Bourassa CV et al.·Am J Hum Genet
2012
The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes.
Rodríguez Cruz PM et al.·Int J Mol Sci
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools