SV2B

Chr 15

synaptic vesicle glycoprotein 2B

Also known as: HsT19680, SLC22B2

NCBI Gene: 9899 ENSG00000185518 UniProt: Q7L1I2

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.63

Clinical Summary— SV2B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

96 VUS of 105 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.000

Z-score 3.20

OE 0.40 (0.26–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.16Z-score

OE missense 0.83 (0.76–0.92)

327 obs / 391.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.63)

0≤0.351.4

Missense OE?0.83 (0.76–0.92)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 13 / 32.7Missense obs/exp: 327 / 391.7Syn Z: 0.83

This gene — mechanism propensity

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

105 submitted variants in ClinVar

ClinVar

Classification Summary

VUS96

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	96	0	96
Likely Benign	2	1	3
Benign	0	1	1
Total	98	2	100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

43 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap SV2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →