SV2A: Synaptic Vesicle Glycoprotein 2A - A Key Target in Epilepsy and Neurobiology
Comprehensive genomic, proteomic, and clinical overview of SV2A, the synaptic vesicle protein 2A gene.
Gene Information Card
| Symbol | SV2A |
|---|---|
| Full Name | Synaptic Vesicle Glycoprotein 2A |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 9900 ncbi.nlm.nih.gov/gene/9900 |
| Ensembl ID | ENSG00000118689 |
| UniProt ID | Q7L0J3 |
| OMIM ID | 185860 |
| HGNC ID | 11466 |
| Aliases | SV2, KIAA0736 |
Description
SV2A (Synaptic Vesicle Glycoprotein 2A) is a protein-coding gene located on chromosome 1q21.2. It encodes a transmembrane glycoprotein that is a component of synaptic vesicle membranes. SV2A is ubiquitously expressed in the brain and is the primary binding site for the antiepileptic drug levetiracetam. The protein is involved in the regulation of vesicle exocytosis, neurotransmitter release, and calcium-dependent synaptic transmission. Loss-of-function mutations in SV2A are associated with epilepsy and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 12 (EIEE12) | Loss-of-function mutations in SV2A impair synaptic vesicle trafficking and neurotransmitter release, leading to early-onset seizures and developmental delay. | ClinVar, OMIM #185860 |
| Developmental and epileptic encephalopathy (DEE) | Heterozygous and homozygous SV2A variants disrupt normal synaptic function, causing severe epilepsy with intellectual disability. | ClinVar, NCBI Gene |
| Levetiracetam response in epilepsy | SV2A is the molecular target of levetiracetam; altered SV2A expression or binding affinity may influence drug efficacy. | UniProt, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 34.2 | High |
| Brain (cerebellum) | 28.7 | High |
| Brain (hippocampus) | 31.5 | High |
| Brain (substantia nigra) | 26.1 | High |
| Spinal cord | 15.8 | Medium |
| Testis | 4.3 | Low |
| Pancreas | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.5 | Neuronal model; high SV2A expression |
| U-87 MG (glioblastoma) | 12.3 | Moderate expression |
| HEK293 (embryonic kidney) | 6.7 | Low endogenous expression |
| HepG2 (hepatocellular carcinoma) | 1.2 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.164G>A (p.Arg55Gln) | Missense | Rare | Reduced protein stability and binding to levetiracetam; associated with epilepsy |
| c.497C>T (p.Thr166Met) | Missense | Rare | Impaired synaptic vesicle trafficking; reported in developmental epileptic encephalopathy |
| c.1084C>T (p.Arg362*) | Nonsense | Very rare | Premature truncation; loss of function; severe early-onset epilepsy |
| c.1327_1328del (p.Leu443Valfs*12) | Frameshift | Very rare | Loss of function; associated with EIEE12 |
Mutation functional classification
Loss of Function (LOF)
Most SV2A pathogenic mutations (nonsense, frameshift, missense with loss of binding) result in loss of protein function, leading to impaired synaptic vesicle exocytosis and neurotransmitter release.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SV2A.
Dominant Negative (DN)
Some heterozygous missense variants may exert dominant-negative effects by interfering with SV2A dimerization or vesicle targeting, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Synaptic vesicle cycle (KEGG: hsa04721)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
• Levetiracetam mechanism of action (DrugBank: DB01202)
Protein Summary
SV2A is a 12-pass transmembrane glycoprotein of 742 amino acids (UniProt Q7L0J3) localized to synaptic vesicle membranes. It contains a large N-terminal cytoplasmic domain and multiple transmembrane helices. The protein binds calcium and is essential for proper synaptic vesicle priming and exocytosis. SV2A is the primary target of the antiepileptic drug levetiracetam, which modulates SV2A activity to reduce neurotransmitter release. Loss of SV2A function leads to impaired calcium-dependent exocytosis and is linked to early-onset epileptic encephalopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SV2A Knockout HEK293 Cell Line | EDJ-KQ6807 | Human | 9900 | Details Get a Quote |
| SV2A Knockout HeLa Cell Line | EDJ-KQ31308 | Human | 9900 | Details Get a Quote |
| SV2A Knockout A-549 Cell Line | EDJ-KQ63756 | Human | 9900 | Details Get a Quote |
| SV2A Knockout HCT 116 Cell Line | EDJ-KQ72216 | Human | 9900 | Details Get a Quote |
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