VAMP7

Chr Y

vesicle associated membrane protein 7

Also known as: SYBL1, TI-VAMP, TIVAMP, VAMP-7

This transmembrane SNARE protein mediates vesicle fusion between late endosomes and lysosomes and is required for lysosomal exocytosis and immune cell degranulation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy with seizures and severe developmental delay. The gene shows tolerance to loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.86
Clinical SummaryVAMP7
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.014
Z-score 1.92
OE 0.41 (0.210.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.66Z-score
OE missense 0.84 (0.720.98)
115 obs / 136.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.210.86)
00.351.4
Missense OE0.84 (0.720.98)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 5 / 12.3Missense obs/exp: 115 / 136.6Syn Z: 0.16
DN
0.83top 10%
GOF
0.6736th %ile
LOF
0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

VAMP7 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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