SV2A

Chr 1AR

synaptic vesicle glycoprotein 2A

Also known as: DEE113, SLC22B1, SV2

NCBI Gene: 9900 ENSG00000159164 UniProt: Q7L0J3 OMIM: 185860

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is one of three related synaptic vesicle proteins. The encoded protein may interact with synaptotagmin to enhance low frequency neurotransmission in quiescent neurons. [provided by RefSeq, Jun 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 113MIM #620772

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 113; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

149

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.41

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — SV2A

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.228

Z-score 4.36

OE 0.24 (0.14–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.12Z-score

OE missense 0.72 (0.66–0.79)

328 obs / 455.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.41)

0≤0.351.4

Missense OE?0.72 (0.66–0.79)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 9 / 38.0Missense obs/exp: 328 / 455.0Syn Z: 0.20

Background carrier burden — how many people carry a rare variant somewhere in SV2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

807 rare PASS variants

Rare truncating (LoF)

1 in 7,400

45 rare PASS variants

Rare synonymous (reference)

1 in 84

384 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SV2A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 8,100
South Asian	~43k	1 in 91	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 100	1 in 6,000
European (Finnish)	~27k	1 in 390	≈ 1 in 13,000
Admixed American	~22k	1 in 66	none seen
African / African American	~21k	1 in 100	≈ 1 in 6,400
East Asian	~20k	1 in 86	none seen
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 96	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓