SV2A
Chr 1ARsynaptic vesicle glycoprotein 2A
Also known as: DEE113, SLC22B1, SV2
SV2A encodes a synaptic vesicle protein that enhances low-frequency neurotransmission by maintaining the readily releasable pool of secretory vesicles and positively regulating vesicle fusion. Autosomal recessive mutations cause developmental and epileptic encephalopathy 113, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.414), suggesting some tolerance to heterozygous loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
130 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 11 | 0 | 12 |
Likely Pathogenic | 2 | 0 | 0 | 0 | 2 |
VUS | 1 | 77 | 4 | 1 | 83 |
Likely Benign | 0 | 3 | 0 | 13 | 16 |
Benign | 0 | 0 | 0 | 5 | 5 |
| Total | 4 | 80 | 15 | 19 | 118 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SV2A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Precision Medicine in the Treatment of Epilepsy
RECRUITINGSocial Disconnection Study
RECRUITINGEarly Post-Traumatic Seizures Prevention Trial (E-PTS Trial)
RECRUITINGMechanistic Studies of Psilocybin in Headache Disorders
RECRUITINGImaging mGluR5 and Synaptic Density in Psychiatric Disorders
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools