SV2A

Chr 1

synaptic vesicle glycoprotein 2A

Also known as: DEE113, SLC22B1, SV2

NCBI Gene: 9900ENSG00000159164UniProt: Q7L0J3

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]

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 113
129
ClinVar variants
14
Pathogenic / LP
0.23
pLI score
5
Active trials
Clinical Summary— SV2A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 82 VUS of 129 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.14–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.66–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 9 / 38.0Missense obs/exp: 328 / 455.0Syn Z: 0.20

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS82
Likely Benign16
Benign5
12
Pathogenic
2
Likely Pathogenic
82
VUS
16
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
2
0
2
VUS
1
76
4
1
82
Likely Benign
0
2
1
13
16
Benign
0
0
0
5
5
Total1781919117

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.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Narrative Review of Brivaracetam: Preclinical Profile and Clinical Benefits in the Treatment of Patients with Epilepsy.
Klein P et al.·Adv Ther
2024Review
PET Imaging in Psychiatric Disorders.
Ferrando R et al.·Semin Nucl Med
2025Review
Discovery and development of SV2A PET tracers: Potential for imaging synaptic density and clinical applications.
Mercier J et al.·Drug Discov Today Technol
2017Review
Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis.
Ohno Y et al.·CNS Neurol Disord Drug Targets
2017Review
Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression.
Asch RH et al.·Neuropsychopharmacology
2024Review
Seletracetam (UCB 44212).
Bennett B et al.·Neurotherapeutics
2007Review
Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging.
Howes O et al.·Neuropsychopharmacology
2024Review
Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil.
Wu PP et al.·Neurosci Bull
2024Review
New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels.
Rogawski MA et al.·Curr Neurol Neurosci Rep
2008Review
Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.
Du Y et al.·CNS Neurosci Ther
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Major Depressive DisorderBipolar DisorderHealthy

Imaging mGluR5 and Synaptic Density in Psychiatric Disorders

ACTIVE NOT RECRUITING
NCT03898297Yale UniversityStarted 2017-01-11
[18F]FPEB[11C]APP311
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Social Disconnection

Social Disconnection Study

RECRUITING
NCT06705348Yale UniversityStarted 2023-05-08
Migraine

Mechanistic Studies of Psilocybin in Headache Disorders

RECRUITING
NCT06464367Phase EARLY_PHASE1Yale UniversityStarted 2025-05-19
PsilocybinPlacebo
SeizuresTraumatic Brain InjuriesTraumatic Brain Injury (TBI) Patients

Early Post-Traumatic Seizures Prevention Trial (E-PTS Trial)

RECRUITING
NCT07072624Phase PHASE4All India Institute of Medical Sciences, JodhpurStarted 2025-07-23
PhenytoinLevetiracetamPlacebo

External Resources

Links to major genomics databases and tools