SV2A

Summary

SV2A (synaptic vesicle glycoprotein 2A, HGNC:20566) is a protein-coding gene on chromosome 1q21.2, encoding Synaptic vesicle glycoprotein 2A (Q7L0J3). Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission.

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.

Source: NCBI Gene 9900 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy 113 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 115 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes
• MANE Select transcript: NM_014849

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20566
Approved symbol	SV2A
Name	synaptic vesicle glycoprotein 2A
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	SV2, KIAA0736, SLC22B1
Ensembl gene	ENSG00000159164
Ensembl biotype	protein_coding
OMIM	185860
Entrez	9900

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000369145, ENST00000369146, ENST00000904148, ENST00000904149, ENST00000923592, ENST00000923593, ENST00000944295

RefSeq mRNA: 3 — MANE Select: NM_014849 NM_001328674, NM_001328675, NM_014849

CCDS: CCDS940

Canonical transcript exons

ENST00000369146 — 13 exons

Exon	Start	End
ENSE00001043663	149908042	149908206
ENSE00001043666	149910570	149910703
ENSE00001043671	149906650	149906856
ENSE00001043672	149911800	149911980
ENSE00001043674	149907700	149907833
ENSE00001043676	149909192	149909280
ENSE00001043678	149905880	149906039
ENSE00001043685	149909801	149909890
ENSE00001043688	149909461	149909571
ENSE00001343910	149917739	149917844
ENSE00001448906	149903318	149905197
ENSE00001448908	149913219	149914187
ENSE00001796232	149910826	149910977

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4415 / max 303.8079, expressed in 1246 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14262	10.6468	1226
14261	1.7947	543

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.42	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.19	gold quality
paraflocculus	UBERON:0005351	98.69	gold quality
substantia nigra pars compacta	UBERON:0001965	98.51	gold quality
frontal pole	UBERON:0002795	98.45	gold quality
superior frontal gyrus	UBERON:0002661	98.44	gold quality
middle temporal gyrus	UBERON:0002771	98.43	gold quality
postcentral gyrus	UBERON:0002581	98.40	gold quality
parietal lobe	UBERON:0001872	98.38	gold quality
primary visual cortex	UBERON:0002436	98.28	gold quality
occipital lobe	UBERON:0002021	98.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.11	gold quality
entorhinal cortex	UBERON:0002728	97.95	gold quality
cerebellar vermis	UBERON:0004720	97.94	gold quality
pons	UBERON:0000988	97.76	gold quality
prefrontal cortex	UBERON:0000451	97.70	gold quality
superior vestibular nucleus	UBERON:0007227	97.67	gold quality
ventral tegmental area	UBERON:0002691	97.60	gold quality
lateral globus pallidus	UBERON:0002476	97.59	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.59	gold quality
frontal cortex	UBERON:0001870	97.51	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.50	gold quality
cerebellum	UBERON:0002037	97.40	gold quality
cerebellar cortex	UBERON:0002129	97.35	gold quality
cerebellar hemisphere	UBERON:0002245	97.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.24	gold quality
middle frontal gyrus	UBERON:0002702	97.13	gold quality
CA1 field of hippocampus	UBERON:0003881	97.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	13.33
E-HCAD-25	yes	9.28
E-GEOD-137537	yes	7.68
E-ANND-3	no	3.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF3, SREBF1

miRNA regulators (miRDB)

142 targeting SV2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104

Literature-anchored findings (GeneRIF, showing 26)

• Synaptic vesicle protein 2 binds adenine nucleotides (PMID:18524768)
• We found no association between genetic variation in SV2A and response to levetiracetam or epilepsy predisposition (PMID:18977120)
• The pattern of SV2A immunoreactivity with reduced neuropil expression and altered cellular and subcellular distribution suggests a possible contribution of SV2A to the epileptogenicity of these malformations of cortical development. (PMID:19220410)
• Botulinum toxin type A (BTA) inhibits the growth of LNCaP human PCa cells in vitro and in vivo. BTA acts on the cells by virtue of the BTA receptor, the SV2 protein. (PMID:19399787)
• the role of SV2A in epileptogenesis in patients with glial tumors is questionable (PMID:20167814)
• expression of SV2A in tumor and peritumoral tissue is correlated to the clinical response to levetiracetam and predicts levetiracetam efficacy (PMID:21795655)
• Data report a combined modelling and mutagenesis study that successfully identifies another 11 residues in synaptic vesicle protein 2A that appear to be involved in ligand binding. (PMID:21936812)
• This study in the German population provides evidence, at a genetic level, for the involvement of the SV2A gene region in schizophrenia. (PMID:23017826)
• High SV2A expression is associated with breast cancer. (PMID:23244111)
• agents that act on the conformation of SV2A might hold great potential in the search for new SV2A-based anticonvulsant therapies (PMID:23530581)
• In classical mesial temporal sclerosis 1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A paralleling synaptic loss. (PMID:23617838)
• The SV2A/FE65 interaction might play a role in synaptic signal transduction. (PMID:24284412)
• The newly identified galactose transport capability of SV2A may have an important role in regulating/modulating synaptic function. (PMID:25326386)
• the way LEV analogues may interact with SV2A (PMID:25692762)
• SV2A expression in the bladder urothelium increases after BoNT-A injection. (PMID:26241848)
• Botulinum neurotoxin type A inhibits synaptic vesicle 2 expression in breast cancer cell lines. (PMID:26339411)
• Expression of SV2A in brain tissue predicts adverse events following levetiracetam in patients with brain tumor-related epilepsy. (PMID:31168673)
• SV2 was highly expressed in neuroblastoma (NB) and can thus be useful marker in NB diagnostics. VMAT1 and VMAT2 were also expressed in NB but similar to syn less reliable as tumor markers. (PMID:31317476)
• In vivo measurement of widespread synaptic loss in Alzheimer’s disease with SV2A PET. (PMID:32400950)
• Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [(11) C]UCB-J positron emission tomography study. (PMID:32944949)
• Differentiation of two human neuroblastoma cell lines alters SV2 expression patterns. (PMID:33588752)
• Validation of SV2A-Targeted PET Imaging for Noninvasive Assessment of Neuroendocrine Differentiation in Prostate Cancer. (PMID:34884893)
• Broadening the phenotypic spectrum of the presumably epilepsy-related SV2A gene variants. (PMID:36758444)
• Loss of SV2A promotes human neural stem cell apoptosis via p53 signaling. (PMID:36780942)
• Reductions in synaptic marker SV2A in early-course Schizophrenia. (PMID:36934603)
• Biallelic variants in the synaptic vesicle glycoprotein 2 A are associated with epileptic encephalopathy. (PMID:37985816)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sv2a	ENSDARG00000059945
mus_musculus	Sv2a	ENSMUSG00000038486
rattus_norvegicus	Sv2a	ENSRNOG00000021182

Paralogs (2): SV2C (ENSG00000122012), SV2B (ENSG00000185518)

Protein

Protein identifiers

Synaptic vesicle glycoprotein 2A — Q7L0J3 (reviewed: Q7L0J3)

All UniProt accessions (1): Q7L0J3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles. (Microbial infection) Receptor for the C.botulinum neurotoxin type A2 (BoNT/A, botA); glycosylation is not essential but enhances the interaction. Probably also serves as a receptor for the closely related C.botulinum neurotoxin type A1.

Subunit / interactions. Interacts with SYT1/synaptotagmin-1 in a calcium-dependent manner. Binds the adapter protein complex AP-2. (Microbial infection) Interacts with C.botulinum neurotoxin type A2 (BoNT/A, botA). Interaction is improved by glycosylation of SV2.

Subcellular location. Presynapse. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Post-translational modifications. Phosphorylation by CK1 of the N-terminal cytoplasmic domain regulates interaction with SYT1. N-glycosylated.

Disease relevance. Developmental and epileptic encephalopathy 113 (DEE113) [MIM:620772] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE113 is an autosomal recessive form characterized by severe early-onset recurrent epilepsy. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Identified as the brain binding-site for the antiepileptic drug levetiracetam/lev.

Similarity. Belongs to the major facilitator superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L0J3-1	1	yes
Q7L0J3-2	2

RefSeq proteins (3): NP_001315603, NP_001315604, NP_055664* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005828	MFS_sugar_transport-like	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR022308	SV2	Family
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR055415	LD_SV2	Domain

Pfam: PF00083, PF07690, PF23894

UniProt features (92 total): helix 25, topological domain 13, transmembrane region 12, strand 12, sequence conflict 7, modified residue 6, turn 6, glycosylation site 3, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
4V11	X-RAY DIFFRACTION	1.95
9OKH	ELECTRON MICROSCOPY	2.39
9OKG	ELECTRON MICROSCOPY	2.58
9OKI	ELECTRON MICROSCOPY	2.67
9OKJ	ELECTRON MICROSCOPY	2.68
9OKF	ELECTRON MICROSCOPY	2.8
8JLE	ELECTRON MICROSCOPY	2.82
8JLG	ELECTRON MICROSCOPY	2.87
8JLC	ELECTRON MICROSCOPY	2.88
8JS8	ELECTRON MICROSCOPY	2.88
8JLH	ELECTRON MICROSCOPY	2.9
9PC9	ELECTRON MICROSCOPY	2.91
8JLF	ELECTRON MICROSCOPY	3.01
8JS9	ELECTRON MICROSCOPY	3.01
9PRS	ELECTRON MICROSCOPY	3.03
9NTC	ELECTRON MICROSCOPY	3.05
8K77	ELECTRON MICROSCOPY	3.11
8UO9	ELECTRON MICROSCOPY	3.3
8JLI	ELECTRON MICROSCOPY	3.38
8YF1	ELECTRON MICROSCOPY	3.38
9PCB	ELECTRON MICROSCOPY	3.42
8YF0	ELECTRON MICROSCOPY	3.49
8UOA	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L0J3-F1	77.14	0.37

Antibody-complex structures (SAbDab): 2 — 8UO9, 8UOA

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 80, 81, 84, 127, 393, 480

Glycosylation sites (3): 498, 548, 573

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5250955	Toxicity of botulinum toxin type D (botD)
R-HSA-5250968	Toxicity of botulinum toxin type A (botA)
R-HSA-5250981	Toxicity of botulinum toxin type F (botF)
R-HSA-5250992	Toxicity of botulinum toxin type E (botE)
R-HSA-1643685	Disease
R-HSA-168799	Neurotoxicity of clostridium toxins
R-HSA-5339562	Uptake and actions of bacterial toxins
R-HSA-5663205	Infectious disease
R-HSA-9824439	Bacterial Infection Pathways

MSigDB gene sets: 269 (showing top): GCANCTGNY_MYOD_Q6, GOBP_NEUROTRANSMITTER_TRANSPORT, TGACCTY_ERR1_Q2, MEF2_02, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, NKX61_01, MODULE_66, MODULE_118, GOBP_EXOCYTOSIS, NF1_Q6_01, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, GNF2_TM4SF2, GOBP_SECRETION

GO Biological Process (5): intracellular calcium ion homeostasis (GO:0006874), synaptic vesicle priming (GO:0016082), neurotransmitter transport (GO:0006836), chemical synaptic transmission (GO:0007268), transmembrane transport (GO:0055085)

GO Molecular Function (2): protein kinase binding (GO:0019901), transmembrane transporter activity (GO:0022857)

GO Cellular Component (15): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), synaptic vesicle (GO:0008021), synaptic vesicle membrane (GO:0030672), neuromuscular junction (GO:0031594), neuron projection (GO:0043005), presynaptic active zone (GO:0048786), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Neurotoxicity of clostridium toxins	4
Uptake and actions of bacterial toxins	1
Bacterial Infection Pathways	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	4
cellular anatomical structure	4
transport	2
cytoplasm	2
presynapse	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
synaptic vesicle exocytosis	1
protein-containing complex assembly	1
exocytic process	1
anterograde trans-synaptic signaling	1
cellular process	1
kinase binding	1
transporter activity	1
transmembrane transport	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
anchoring junction	1
exocytic vesicle	1
synaptic vesicle	1
exocytic vesicle membrane	1
plasma membrane bounded cell projection	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SV2A	SYP	P08247	975
SV2A	SYT1	P21579	928
SV2A	GP2	P55259	900
SV2A	SYT2	Q8N9I0	735
SV2A	VAMP2	P19065	700
SV2A	SYN1	P17600	692
SV2A	SNAP25	P13795	678
SV2A	SYNGR3	O43761	644
SV2A	SLC17A7	Q9P2U7	627
SV2A	SYN2	Q92777	625
SV2A	STX1B	P61266	616
SV2A	SYN3	O14994	610
SV2A	RAB3A	P20336	593
SV2A	DLG4	P78352	592
SV2A	PPT2	Q9UMR5	584

IntAct

26 interactions, top by confidence:

A	B	Type	Score
SV2A	EXTL3	psi-mi:“MI:0914”(association)	0.530
SV2A	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
SV2A	ATXN1	psi-mi:“MI:0915”(physical association)	0.370
	TSPO	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
APBB1	ATP2A2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
SV2A	ILVBL	psi-mi:“MI:0914”(association)	0.350
AP2M1	C1orf226	psi-mi:“MI:0914”(association)	0.350
UPK2	NRP2	psi-mi:“MI:0914”(association)	0.350
AP2M1	PER1	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
P/V	ESYT2	psi-mi:“MI:0914”(association)	0.350
	ILVBL	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270
FYN	SV2A	psi-mi:“MI:0915”(physical association)	0.000
SV2A	ETS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (101): SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), DNAJC5 (FRET), SV2A (Affinity Capture-MS), SV2A (Proximity Label-MS), SV2A (Proximity Label-MS), SV2A (Two-hybrid), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS), SV2A (Affinity Capture-MS)

ESM2 similar proteins: A2X8A7, A2Y8U6, A6ZIQ8, B8AF63, B8AT51, B8BDK8, B9FMX4, F4IKF6, G2WS43, O22216, O35776, O57424, O57427, O80605, P70312, Q02563, Q0JAW2, Q0VA82, Q29397, Q2UMJ2, Q2V4F9, Q3TIT8, Q3TMP8, Q496J9, Q4R4X3, Q5EAU0, Q5F361, Q5F3N0, Q5R4L9, Q5ZL05, Q658H5, Q69ZS6, Q6EPQ3, Q6GPQ3, Q6YK44, Q7L0J3, Q8BH31, Q8BM85, Q8GY97, Q8NCC5

Diamond homologs: A0R5K5, A2RJJ9, B4TES5, D0CCT2, E8ZB61, O08966, O15245, O24723, O30513, O52733, P0A0J4, P0A0J5, P0A0J6, P0A0J7, P0A4K4, P0A4K5, P0AE24, P0AE25, P45598, P77228, P77589, P94493, Q02563, Q21455, Q29397, Q3E9A0, Q43975, Q4R4X3, Q51955, Q5EXK5, Q5HHX4, Q5R4L9, Q63089, Q69ZS6, Q6FFF7, Q6GBD5, Q6GIU7, Q7L0J3, Q7L1I2, Q9I6Q3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SV2A	“up-regulates quantity”	SYT1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

115 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	79
Likely benign	15
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3775209	NM_014849.5(SV2A):c.1519C>T (p.Arg507Ter)	Pathogenic
2504572	NM_014849.5(SV2A):c.865C>T (p.Arg289Ter)	Likely pathogenic
4685002	NM_014849.5(SV2A):c.1147C>T (p.Arg383Ter)	Likely pathogenic

SpliceAI

2263 predictions. Top by Δscore:

Variant	Effect	Δscore
1:149906047:C:CT	acceptor_gain	1.0000
1:149906047:C:T	acceptor_gain	1.0000
1:149906048:A:T	acceptor_gain	1.0000
1:149906644:CCTTA:C	donor_loss	1.0000
1:149906645:CTTA:C	donor_loss	1.0000
1:149906646:TTA:T	donor_loss	1.0000
1:149906647:TACCA:T	donor_loss	1.0000
1:149906648:A:AG	donor_loss	1.0000
1:149906649:CCAAG:C	donor_gain	1.0000
1:149906852:CAGGT:C	acceptor_gain	1.0000
1:149906854:GGT:G	acceptor_gain	1.0000
1:149906857:C:CC	acceptor_gain	1.0000
1:149906864:C:CT	acceptor_gain	1.0000
1:149907694:CCTTA:C	donor_loss	1.0000
1:149907695:CTTAC:C	donor_loss	1.0000
1:149907696:TTAC:T	donor_loss	1.0000
1:149907697:TACCA:T	donor_loss	1.0000
1:149907698:A:AC	donor_gain	1.0000
1:149907698:ACCA:A	donor_loss	1.0000
1:149907699:C:CC	donor_gain	1.0000
1:149907831:AACCT:A	acceptor_loss	1.0000
1:149907834:C:T	acceptor_loss	1.0000
1:149908037:CATA:C	donor_gain	1.0000
1:149908039:TACTT:T	donor_loss	1.0000
1:149908040:A:AC	donor_gain	1.0000
1:149908041:C:CA	donor_gain	1.0000
1:149908041:CT:C	donor_gain	1.0000
1:149908041:CTT:C	donor_gain	1.0000
1:149908041:CTTG:C	donor_gain	1.0000
1:149908041:CTTGT:C	donor_gain	1.0000

AlphaMissense

4873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:149905183:C:T	G687D	1.000
1:149905184:C:G	G687R	1.000
1:149905880:C:A	R682M	1.000
1:149905929:A:G	W666R	1.000
1:149905929:A:T	W666R	1.000
1:149905959:A:G	C656R	1.000
1:149909804:G:C	F392L	1.000
1:149909804:G:T	F392L	1.000
1:149909805:A:C	F392C	1.000
1:149909805:A:G	F392S	1.000
1:149909806:A:G	F392L	1.000
1:149909837:G:C	N381K	1.000
1:149909837:G:T	N381K	1.000
1:149909859:A:G	L374P	1.000
1:149910574:A:G	L362P	1.000
1:149910586:G:T	P358H	1.000
1:149910658:C:A	R334M	1.000
1:149910658:C:G	R334T	1.000
1:149910660:C:A	W333C	1.000
1:149910660:C:G	W333C	1.000
1:149910662:A:G	W333R	1.000
1:149910662:A:T	W333R	1.000
1:149910972:C:T	G270E	1.000
1:149911950:C:T	G218E	1.000
1:149911951:C:G	G218R	1.000
1:149911951:C:T	G218R	1.000
1:149911963:C:G	G214R	1.000
1:149913263:G:T	A193D	1.000
1:149913549:A:G	Y98H	1.000
1:149905062:G:C	S727R	0.999

dbSNP variants (sampled 300 via entrez): RS1000695415 (1:149916428 G>C,T), RS1001150107 (1:149916160 C>T), RS1001254212 (1:149917171 C>T), RS1001346872 (1:149904067 C>T), RS1001423031 (1:149910532 C>T), RS1001476594 (1:149910275 G>C), RS1001676766 (1:149904649 G>A,C), RS1002128920 (1:149904902 C>A,G,T), RS1002203466 (1:149916110 G>A), RS1002430462 (1:149909162 A>G), RS1002660736 (1:149915813 C>G,T), RS1002726990 (1:149903077 C>T), RS1003082950 (1:149902828 A>C,G), RS1003435524 (1:149908139 G>A,C), RS1003894506 (1:149905676 C>T)

Disease associations

OMIM: gene MIM:185860 | disease phenotypes: MIM:620772

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 113	Moderate	Semidominant
epilepsy	Limited	Autosomal dominant

Mondo (3): developmental and epileptic encephalopathy 113 (MONDO:0958330), neurodevelopmental disorder (MONDO:0700092), epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000648	Optic atrophy
HP:0000768	Pectus carinatum
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0002020	Gastroesophageal reflux
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002179	Opisthotonus
HP:0002376	Developmental regression
HP:0002553	Highly arched eyebrow
HP:0003593	Infantile onset
HP:0008897	Postnatal growth retardation
HP:0010851	EEG with burst suppression
HP:0011448	Ankle clonus
HP:0012707	Elevated brain lactate level by MRS
HP:0012708	Reduced brain N-acetyl aspartate level by MRS
HP:0025373	Interictal EEG abnormality
HP:0032792	Tonic seizure
HP:0032794	Myoclonic seizure
HP:0033725	Thin corpus callosum
HP:0100704	Cerebral visual impairment

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000175_50	Height	1.000000e-10
GCST002702_110	Height	1.000000e-12
GCST007485_2	Anthropometric traits	1.000000e-85
GCST007490_5	Anthropometric traits (multi-trait analysis)	1.000000e-53
GCST008480_1	Lung function (FEV1)	2.000000e-08
GCST008839_163	Height	6.000000e-39
GCST90020028_589	Hip circumference adjusted for BMI	8.000000e-09
GCST90020028_616	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004324	body weights and measures
EFO:0004314	forced expiratory volume
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1998 (SINGLE PROTEIN), CHEMBL4665594 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Atypical SLC22B subfamily

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
brivaracetam	Inhibition	7.0	pIC50
levetiracetam	Inhibition	5.8	pKi

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, increases expression	3
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Heroin	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5119099	Binding	Binding affinity to human SV2A in presence of levetiracetam by radioligand binding assay	Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4FK	1321N1-SV2A-KO-c14	Cancer cell line	Male
CVCL_D4FL	1321N1-SV2A-KO-c17	Cancer cell line	Male
CVCL_F1TL	HyCyte SH-SY5Y KO-hSV2A	Cancer cell line	Female
CVCL_F1TM	HyCyte SH-SY5Y KO-hSV2A hSV2C	Cancer cell line	Female

Clinical trials (associated diseases)

501 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy