SV2B

Chr 15

synaptic vesicle glycoprotein 2B

Also known as: HsT19680, SLC22B2

The protein is a synaptic vesicle membrane protein that regulates vesicle trafficking and exocytosis in neural and endocrine cells. Mutations cause autosomal recessive infantile epileptic encephalopathy, typically with onset in early infancy. The gene is highly constrained against loss-of-function variants (LOEUF 0.63), indicating that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.63
Clinical SummarySV2B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
0.63LOEUF
pLI 0.000
Z-score 3.20
OE 0.40 (0.260.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.16Z-score
OE missense 0.83 (0.760.92)
327 obs / 391.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.260.63)
00.351.4
Missense OE0.83 (0.760.92)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 13 / 32.7Missense obs/exp: 327 / 391.7Syn Z: 0.83
DN
0.80top 25%
GOF
0.75top 25%
LOF
0.1894th %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

SV2B · 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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