SCN2A

Summary

SCN2A (sodium voltage-gated channel alpha subunit 2, HGNC:10588) is a protein-coding gene on chromosome 2q24.3, encoding Sodium channel protein type 2 subunit alpha (Q99250). Mediates the voltage-dependent sodium ion permeability of excitable membranes. It is haploinsufficient (ClinGen: sufficient evidence).

Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6326 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +10 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 3,011 total — 353 pathogenic, 302 likely-pathogenic
• Phenotypes (HPO): 208
• Druggable target: yes — 99 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001040142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10588
Approved symbol	SCN2A
Name	sodium voltage-gated channel alpha subunit 2
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Nav1.2, HBSCII, HBSCI
Ensembl gene	ENSG00000136531
Ensembl biotype	protein_coding
OMIM	182390
Entrez	6326

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 8 protein_coding, 8 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000283256, ENST00000375437, ENST00000424833, ENST00000480032, ENST00000486878, ENST00000631182, ENST00000635945, ENST00000636071, ENST00000636135, ENST00000636384, ENST00000636662, ENST00000636769, ENST00000636985, ENST00000637266, ENST00000637367, ENST00000638151, ENST00000640791, ENST00000673831, ENST00000673883, ENST00000674133

RefSeq mRNA: 5 — MANE Select: NM_001040142 NM_001040142, NM_001040143, NM_001371246, NM_001371247, NM_021007

CCDS: CCDS33313, CCDS33314

Canonical transcript exons

ENST00000375437 — 27 exons

Exon	Start	End
ENSE00003469366	165309352	165309443
ENSE00003476134	165312025	165312088
ENSE00003480100	165354192	165354671
ENSE00003515214	165367217	165367371
ENSE00003520813	165377597	165377650
ENSE00003534381	165326852	165326984
ENSE00003577130	165331330	165331568
ENSE00003578392	165344555	165344911
ENSE00003583124	165323156	165323500
ENSE00003607689	165295773	165296090
ENSE00003618158	165297017	165297135
ENSE00003622830	165313902	165314108
ENSE00003624540	165310323	165310595
ENSE00003632501	165342296	165342469
ENSE00003637082	165307848	165307937
ENSE00003646557	165308666	165308794
ENSE00003650170	165315471	165315758
ENSE00003667200	165313620	165313761
ENSE00003673050	165365143	165365263
ENSE00003692338	165374685	165374966
ENSE00003768497	165386746	165387016
ENSE00003793096	165380592	165380729
ENSE00003797234	165381093	165381197
ENSE00003797951	165370126	165370299
ENSE00003798346	165373225	165373347
ENSE00003843655	165239414	165239640
ENSE00003848820	165388629	165392304

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 98.77.

FANTOM5 (CAGE): breadth broad, TPM avg 15.1310 / max 2181.7494, expressed in 368 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23415	7.1018	138
23416	5.8147	137
23418	1.8434	304
23417	0.2913	68
23419	0.0336	17
23426	0.0286	13
23414	0.0175	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.77	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.30	gold quality
cerebellar vermis	UBERON:0004720	96.78	gold quality
entorhinal cortex	UBERON:0002728	96.62	gold quality
cerebellar cortex	UBERON:0002129	96.33	gold quality
parietal lobe	UBERON:0001872	96.27	gold quality
cerebellar hemisphere	UBERON:0002245	96.27	gold quality
postcentral gyrus	UBERON:0002581	96.21	gold quality
superior frontal gyrus	UBERON:0002661	96.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.95	gold quality
cerebellum	UBERON:0002037	95.77	gold quality
endothelial cell	CL:0000115	95.41	gold quality
primary visual cortex	UBERON:0002436	94.15	gold quality
occipital lobe	UBERON:0002021	94.10	gold quality
pons	UBERON:0000988	93.83	gold quality
prefrontal cortex	UBERON:0000451	91.75	gold quality
cortical plate	UBERON:0005343	91.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.83	gold quality
superior vestibular nucleus	UBERON:0007227	90.66	gold quality
frontal cortex	UBERON:0001870	90.52	gold quality
cerebral cortex	UBERON:0000956	89.86	gold quality
substantia nigra pars compacta	UBERON:0001965	89.69	gold quality
neocortex	UBERON:0001950	89.43	gold quality
lateral globus pallidus	UBERON:0002476	88.85	gold quality
telencephalon	UBERON:0001893	88.02	gold quality
temporal lobe	UBERON:0001871	87.96	gold quality
right frontal lobe	UBERON:0002810	87.72	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.46	gold quality
Ammon’s horn	UBERON:0001954	87.33	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	480.60
E-GEOD-93593	yes	309.30
E-CURD-119	yes	45.64
E-ANND-3	yes	7.71
E-GEOD-84465	yes	6.46
E-GEOD-83139	yes	3.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IL10, KDM5C, KLF4, RCOR1, REST, TNF

miRNA regulators (miRDB)

169 targeting SCN2A, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• in autism families, the variant R1902C in SCN2A is located in the calmodulin binding site and was found to reduce binding affinity for calcium-bound calmodulin. (PMID:12610651)
• We found a nonsense mutation of SCN2A in a patient with intractable epilepsy and severe mental decline. The phenotype is like severe myoclonic epilepsy in infancy but distinct because of partial epilepsy, delayed onset and no temperature sensitivity (PMID:15028761)
• a role for the hemizygous deletion of not one but two sodium channel genes (SCN1A and SCN2A) in another complicated and more severe epileptic phenotype. (PMID:15249644)
• Calmodulin mediates Ca2+ sensitivity of Nav1.2 and Nav1.5 sodium channels (PMID:15316014)
• Although data suggest that SCN2A1 activity does not directly influence membrane potential, intracellular Ca(2+) release, or proliferation in normal human pulmonary artery smooth muscle cells, its physiological functions remain unresolved. (PMID:16052353)
• Genetic interaction between the combined mild alleles of monogenic epilepsy genes KCNQ2 and SCN2A1 results in severe epilepsy in transgenic mice. (PMID:16464983)
• Data show that the varied effects of beta1 and beta2 on Nav1.5 and Nav1.2 gating are apparently synergistic and highlight the complex manner, through subunit- and sugar-dependent mechanisms, by which Nav activity is modulated. (PMID:16847056)
• The SCN2A gene was tested for a possible role in hippocampal abnormalities in familial mesial temporal lobe epilepsy. We conclusively ruled out the SCN2A gene as a candidate in FMTLE. (PMID:16914293)
• two large families with benign familial neonatal-infantile seizure (BFNIS) and novel SCN2A mutations; the families had 12 & 9 affected individuals, respectively, with phenotypes consistent with BFNIS; two mutations were discovered in SCN2A (E430Q; I1596S) (PMID:17386050)
• analysis of neonatal & adult splice forms of NaV1.2 with a benign familial neonatal-infantile seizures mutation; developmentally regulated NaV1.2 splicing may be one mechanism that counters the normally high excitability of neonatal neurons (PMID:17467289)
• Characterization of 5’ untranslated regions SCN2A, and identification of cis-conserved noncoding sequences (PMID:17544618)
• In south china, the R188W mutation of the SCN2A gene not releate to children with febrile seizures. (PMID:17641256)
• Allele frequencies of both the D2S111 and the D2S124 polymorphisms of the SCN2A gene were not significantly different between cases with a specific idiopathic generalized epilepsy subtype (with generalized tonic-clonic seizures) and healthy controls. (PMID:17715289)
• Nav1.2 immunostaining was not observed along demyelinated axons in chronic lesions but was expressed by scar and reactive astrocytes within the plaque. (PMID:17805013)
• SCN2A gene mutations are associated with inherited benign neonatal-infantile epilepsy. (PMID:18479388)
• The association of antiepileptic drugs responsiveness with genetic polymorphisms was investigated and any association with mRNA expression of the neuronal sodium channels was correlated. (PMID:18784617)
• Clinically significant mutations identified in the C-terminal region of NaV1 sodium channels cluster in the helix I-IV interface and the helix II-III interhelical segment or in helices III and IV of the NaV1.2 (1777-1882) structure. (PMID:19129176)
• Data demonstrate that the two N-terminal alternatively spliced FGF14 variants, FGF14-1a and FGF14-1b, differentially regulate currents produced by Nav1.2 and Nav1.6 channels. (PMID:19465131)
• The direct effect of heat on Nav1.2 channels localized to the site of action potential initiation potentially causes a profound increase in neuronal excitability. This is likely to contribute to febrile seizure genesis. (PMID:19743470)
• This finding suggests that both nonsense mutations and missense SCN2A mutations cause Dravet syndrome. (PMID:19783390)
• de novo mutations SCN2A-E1211K, -I1473M, and -R102X indicate that SCN2A is an etiologic candidate underlying a variety of intractable childhood epilepsies (PMID:19786696)
• Deletions in SCN2A gene is associated with autistic features and developmental delay. (PMID:20346423)
• Transient expression of seizures occur due to a gain-of-function of mutant Na(V)1.2 channel. (PMID:20371507)
• Genetic variants in the voltage-gated ion channel SCN2A dramatically influence the phenotype of mice carrying an SCN1A mutation as well as the seizures caused by the SCN1A mutation. (PMID:21156207)
• We studied the developmental changes of Na(v)1.1 and Na(v)1.2 in the human hippocampus and temporal lobe (PMID:21377452)
• Thermodynamic and structural studies of Calmodulin (CaM)-Na(v)1.2(IQp) interactions show that apo and (Ca(2+))(4)-CaM adopt distinct conformations that both permit tight association with Na(v)1.2(IQp) during gating. (PMID:21439835)
• Environmental enrichment from birth reduces spontaneous seizures and neuronal damage in the Q54 model of temporal lobe epilepsy. (PMID:21762452)
• Functional studies of SCN2A mutations show that they can cause divergent biophysical defects in Na(V)1.2 and impair cell surface expressions[review] (PMID:22029951)
• association of the gene SCN2A, previously identified in epilepsy syndromes, with the risk of autism (PMID:22495306)
• The results of this study shown that both A1685V (GEFS+) and A1685D (SMEI) mutant Nav1.1 channels are characterized by complete loss of function when they are expressed alone (PMID:22525008)
• This finding suggests that SCN2A mutation is a predisposing factor for acute encephalopathy. (PMID:22591750)
• This study demonistrated the detailed functional analysis of Na(v)1.2 mutant, R1312T, which was originally found in a child with Dravet syndrome. (PMID:22677033)
• This study demonistrated that associated with a duplication of the SCN2A and SCN3A gene cluster on 2q24 in patient with early onset epilepsy. (PMID:23016767)
• Identification of a novel SCN2A mutation in a family with infantile seizures with onset between 6 and 8 months provides further confirmation that this gene is involved in families with a delayed age of onset. (PMID:23360469)
• study identified a de novo SCN2A mutation as the etiology for Ohtahara syndrome in monozygotic twins associated with a unique dentate-olivary dysplasia in the deceased twin (PMID:23550958)
• Mutation of SCN2A induces neuronal hyperexcitability, resulting in infantile epilepsy with favorable outcome (PMID:23758435)
• An SCN2A missense mutation is associated with infantile spasms and bitemporal hypometabolism. (PMID:23827426)
• Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. (PMID:23859570)
• SCN2A mutations are an important genetic cause of Ohtahara syndrome. Given the wide clinical spectrum associated with SCN2A mutations, genetic testing for SCN2A should be considered for children with different epileptic conditions. (PMID:23935176)
• Following SCN2A knockdown, the concentration of Cu-Zn SOD declined and the si-SCN2A vector group showed a repeated discharge. (PMID:24220630)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scn2a	ENSMUSG00000075318
rattus_norvegicus	Scn2a	ENSRNOG00000005018

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), SCN1A (ENSG00000144285), CACNA1B (ENSG00000148408), CACNA1C (ENSG00000151067), CATSPER3 (ENSG00000152705), SCN3A (ENSG00000153253), CACNA1D (ENSG00000157388), TPCN2 (ENSG00000162341), CATSPER2 (ENSG00000166762), SCN11A (ENSG00000168356), SCN9A (ENSG00000169432), CATSPER1 (ENSG00000175294), SCN5A (ENSG00000183873), SCN10A (ENSG00000185313), TPCN1 (ENSG00000186815), CATSPER4 (ENSG00000188782), CACNA1H (ENSG00000196557), SCN8A (ENSG00000196876), CACNA1E (ENSG00000198216)

Protein

Protein identifiers

Sodium channel protein type 2 subunit alpha — Q99250 (reviewed: Q99250)

Alternative names: HBSC II, Sodium channel protein brain II subunit alpha, Sodium channel protein type II subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.2

All UniProt accessions (11): A0A0D9SGG2, A0A1B0GTS6, A0A1B0GTX0, A0A1B0GW40, A0A1B0GW67, A0A1B0GWA6, A0A669KAR0, A0A669KBL5, A0A669KBM3, Q99250, F6U291

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory.

Subunit / interactions. Heterooligomer of a large alpha subunit and a smaller beta subunit. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Heterooligomer with SCN1B or SCN3B; non-covalently linked. Interacts with NEDD4L. Interacts with CALM. Interacts with TMEM233. Interacts with the conotoxin GVIIJ. Interacts with the spider beta/delta-theraphotoxin-Pre1a. Interacts with the conotoxin KIIIA. Interacts with the spider protoxin-II.

Subcellular location. Cell membrane.

Post-translational modifications. May be ubiquitinated by NEDD4L; which would promote its endocytosis. Phosphorylation at Ser-1506 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents. Sumoylated at Lys-38. Sumoylation is induced by hypoxia, increases voltage-gated sodium current and mediates the early response to acute hypoxia in neurons. Sumoylated SCN2A is located at the cell membrane.

Disease relevance. Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745] A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 11 (DEE11) [MIM:613721] An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. The disease is caused by variants affecting the gene represented in this entry. Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy. Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD. Episodic ataxia 9 (EA9) [MIM:618924] An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.2/SCN2A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99250-1	1, Adult, 6A	yes
Q99250-2	2, Neonatal, 6N

RefSeq proteins (5): NP_001035232, NP_001035233, NP_001358175, NP_001358176, NP_066287 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR001696	Na_channel_asu	Family
IPR005821	Ion_trans_dom	Domain
IPR010526	Na_trans_assoc_dom	Domain
IPR024583	Na_trans_cytopl	Domain
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR043203	VGCC_Ca_Na	Family
IPR044564	Na_chnl_inactivation_gate	Domain
IPR058542	IQ_SCN5A_C	Domain

Pfam: PF00520, PF06512, PF11933, PF24609

Catalyzed reactions (Rhea), 1 shown:

• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (351 total): sequence variant 112, helix 67, topological domain 29, transmembrane region 24, modified residue 24, turn 21, strand 19, site 11, glycosylation site 10, disulfide bond 7, region of interest 6, compositionally biased region 5, intramembrane region 4, sequence conflict 4, repeat 4, chain 1, cross-link 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4RLY	X-RAY DIFFRACTION	2.5
6J8E	ELECTRON MICROSCOPY	3
4JPZ	X-RAY DIFFRACTION	3.02
2KAV	SOLUTION NMR
6BUT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99250-F1	69.28	0.17

Functional residue map

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

Catalytic / active sites (11): 330 (binds mu-conotoxin kiiia); 362 (binds mu-conotoxin kiiia); 909 (binds scn2b; via carbonyl oxygen); 916 (binds mu-conotoxin kiiia; via amide nitrogen); 920 (binds mu-conotoxin kiiia; via carbonyl oxygen); 945 (binds mu-conotoxin kiiia); 949 (binds mu-conotoxin kiiia); 1374 (binds mu-conotoxin kiiia; via amide nitrogen); 1429 (binds mu-conotoxin kiiia); 1443 (binds mu-conotoxin kiiia); 1489 (important for channel closure)

Post-translational modifications (25): 686, 687, 721, 1506, 1930, 1943, 1963, 1966, 1971, 38, 4, 468, 471, 484, 526, 528, 531, 553, 554, 558 …

Disulfide bonds (7): 278–338, 910, 910, 912–918, 950–959, 1366–1386, 1731–1746

Glycosylation sites (10): 212, 285, 291, 297, 303, 308, 340, 1368, 1382, 1393

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5576892	Phase 0 - rapid depolarisation
R-HSA-9717207	Sensory perception of sweet, bitter, and umami (glutamate) taste
R-HSA-1266738	Developmental Biology
R-HSA-373760	L1CAM interactions
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-5576891	Cardiac conduction
R-HSA-9675108	Nervous system development
R-HSA-9709957	Sensory Perception
R-HSA-9717189	Sensory perception of taste

MSigDB gene sets: 599 (showing top): GOBP_MEMORY, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, GOBP_MUSCLE_CONTRACTION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_ENSHEATHMENT_OF_NEURONS, chr2q24, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP

GO Biological Process (19): sodium ion transport (GO:0006814), nervous system development (GO:0007399), memory (GO:0007613), intrinsic apoptotic signaling pathway in response to osmotic stress (GO:0008627), neuronal action potential (GO:0019228), sodium ion transmembrane transport (GO:0035725), myelination (GO:0042552), neuron apoptotic process (GO:0051402), cellular response to hypoxia (GO:0071456), cardiac muscle cell action potential involved in contraction (GO:0086002), action potential (GO:0001508), regulation of heart rate (GO:0002027), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), transmembrane transport (GO:0055085), cardiac muscle cell action potential (GO:0086001), regulation of muscle system process (GO:0090257), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (6): voltage-gated sodium channel activity (GO:0005248), calmodulin binding (GO:0005516), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), sodium channel activity (GO:0005272), protein binding (GO:0005515)

GO Cellular Component (6): voltage-gated sodium channel complex (GO:0001518), plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), node of Ranvier (GO:0033268), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
L1CAM interactions	1
Cardiac conduction	1
Sensory perception of taste	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Developmental Biology	1
Sensory Perception	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
action potential	2
regulation of biological quality	2
transport	2
monoatomic ion transmembrane transport	2
cellular anatomical structure	2
metal ion transport	1
system development	1
learning or memory	1
cellular response to osmotic stress	1
intrinsic apoptotic signaling pathway	1
transmission of nerve impulse	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
axon ensheathment	1
apoptotic process	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
regulation of membrane potential	1
regulation of heart contraction	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
muscle system process	1
regulation of system process	1
monoatomic cation transport	1
sodium channel activity	1
protein binding	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1
binding	1
sodium channel complex	1
plasma membrane protein complex	1
membrane	1

Protein interactions and networks

STRING

2714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCN2A	ANK3	Q12955	937
SCN2A	SCN1B	Q07699	930
SCN2A	PRRT2	Q7Z6L0	898
SCN2A	KCNQ2	O43526	887
SCN2A	SCN1A	P35498	875
SCN2A	NAV1	Q8NEY1	871
SCN2A	SCN4B	Q8IWT1	865
SCN2A	PCDH19	Q8TAB3	844
SCN2A	STXBP1	P61764	833
SCN2A	CALM1	P02593	825
SCN2A	HBB	P02023	820
SCN2A	CDKL5	O76039	813
SCN2A	SCN3B	Q9NY72	808
SCN2A	KCNA1	Q09470	791
SCN2A	PCDH10	Q9P2E7	781

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CALM1	FGF13	psi-mi:“MI:0915”(physical association)	0.700
SCN2A	CALM1	psi-mi:“MI:0915”(physical association)	0.690
SCN2A	ELAVL3	psi-mi:“MI:0915”(physical association)	0.500
Dlg4	SCN2A	psi-mi:“MI:0407”(direct interaction)	0.440
SCN2A	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.400
SCN2A	ATP5PD	psi-mi:“MI:0915”(physical association)	0.400
	CALM1	psi-mi:“MI:0915”(physical association)	0.400
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ARHGEF10L	SCN2A	psi-mi:“MI:0915”(physical association)	0.000
MPP3	SCN2A	psi-mi:“MI:0915”(physical association)	0.000
RNF130	SCN2A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (79): SCN2A (Proximity Label-MS), SCN2A (Proximity Label-MS), SCN2A (Affinity Capture-MS), SCN2A (Cross-Linking-MS (XL-MS)), TPT1 (Cross-Linking-MS (XL-MS)), SCN2A (Cross-Linking-MS (XL-MS)), SCN2A (Cross-Linking-MS (XL-MS)), CALM2 (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS), IGF2BP2 (Affinity Capture-MS), RARG (Affinity Capture-MS), DNAJC16 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), KARS (Affinity Capture-MS), GNAI1 (Affinity Capture-MS)

ESM2 similar proteins: A2APX8, A2ASI5, B1AWN6, C9D7C2, D0E0C2, O08562, O35505, O46669, O73700, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15381, P15389, P15390, P22002, P27732, P35498, P35499, P35500, Q01815, Q07652, Q13936, Q14524, Q15858, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5, Q2XVR6, Q2XVR7, Q62205, Q62968, Q6QIY3

Diamond homologs: A2APX8, A2ASI5, B1AWN6, B1AYL1, D0E0C2, F1LQQ7, O00555, O08562, O46669, O73705, O73706, O73707, O88420, O88457, P02719, P04774, P04775, P08104, P0DMA5, P15389, P15390, P27884, P35498, P35499, P35500, P54282, P56699, P97445, Q01118, Q02789, Q05973, Q14524, Q15858, Q15878, Q20JQ7, Q28371, Q28644, Q2XVR3, Q2XVR4, Q2XVR5

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
RCOR1	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
REST	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
SCN2A	“up-regulates quantity”	sodium(1+)	relocalization
FGF13	“down-regulates activity”	SCN2A	binding
FGF12	“down-regulates activity”	SCN2A	binding
FGF14	“down-regulates activity”	SCN2A	binding
FGF11	“down-regulates activity”	SCN2A	binding
SCN2A	up-regulates	Action_potential
“CoREST-HDAC complex”	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
GSK3B	“down-regulates activity”	SCN2A	phosphorylation
PKA	“down-regulates activity”	SCN2A	phosphorylation
PKC	“down-regulates activity”	SCN2A	phosphorylation
CSNK2A3	“up-regulates activity”	SCN2A	phosphorylation
CSNK2B	“up-regulates activity”	SCN2A	phosphorylation
CSNK2A1	“up-regulates activity”	SCN2A	phosphorylation
CSNK2A2	“up-regulates activity”	SCN2A	phosphorylation
NEDD4L	“down-regulates quantity by destabilization”	SCN2A	ubiquitination
TNF	“up-regulates quantity by expression”	SCN2A	“transcriptional regulation”
TNF	“up-regulates activity”	SCN2A
KDM5C	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
IL10	“down-regulates quantity by repression”	SCN2A	“transcriptional regulation”
phenytoin	“down-regulates activity”	SCN2A	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

3011 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	353
Likely pathogenic	302
Uncertain significance	1250
Likely benign	707
Benign	131

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1000049	NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val)	Pathogenic
1013421	NM_001040142.2(SCN2A):c.4948C>T (p.Leu1650Phe)	Pathogenic
1066198	NM_001040142.2(SCN2A):c.4551+1G>A	Pathogenic
1068258	NM_001040142.2(SCN2A):c.4501A>G (p.Met1501Val)	Pathogenic
1070304	NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr)	Pathogenic
1071664	NM_001040142.2(SCN2A):c.718del (p.Ala240fs)	Pathogenic
1071677	NM_001040142.2(SCN2A):c.1497del (p.Glu500fs)	Pathogenic
1072191	NM_001040142.2(SCN2A):c.1267G>T (p.Val423Leu)	Pathogenic
1073234	NM_001040142.2(SCN2A):c.4533dup (p.Pro1512fs)	Pathogenic
1074161	NM_001040142.2(SCN2A):c.3782G>A (p.Trp1261Ter)	Pathogenic
1074300	NM_001040142.2(SCN2A):c.4543C>T (p.Arg1515Ter)	Pathogenic
1074301	NM_001040142.2(SCN2A):c.4787T>G (p.Ile1596Ser)	Pathogenic
1098322	NM_001040142.2(SCN2A):c.1940del (p.Ala647fs)	Pathogenic
1173107	NM_001040142.2(SCN2A):c.330C>A (p.Tyr110Ter)	Pathogenic
1180439	NM_001040142.2(SCN2A):c.986dup (p.Leu329fs)	Pathogenic
1196824	NM_001040142.2(SCN2A):c.5405G>A (p.Trp1802Ter)	Pathogenic
1198013	NM_001040142.2(SCN2A):c.721del (p.Ala240_Leu241insTer)	Pathogenic
1206719	NM_001040142.2(SCN2A):c.476+1G>A	Pathogenic
1219256	NM_001040142.2(SCN2A):c.1729del (p.Leu577fs)	Pathogenic
1256055	NM_001040142.2(SCN2A):c.2588C>A (p.Ser863Tyr)	Pathogenic
12876	NM_001040142.2(SCN2A):c.3988C>T (p.Leu1330Phe)	Pathogenic
12877	NM_001040142.2(SCN2A):c.4687C>G (p.Leu1563Val)	Pathogenic
12880	NM_001040142.2(SCN2A):c.3956G>A (p.Arg1319Gln)	Pathogenic
1298832	NM_001040142.2(SCN2A):c.2017-2A>G	Pathogenic
1300201	NM_001040142.2(SCN2A):c.4018G>A (p.Val1340Ile)	Pathogenic
130220	NM_001040142.2(SCN2A):c.3374del (p.Glu1125fs)	Pathogenic
1318908	NM_001040142.2(SCN2A):c.718G>T (p.Ala240Ser)	Pathogenic
1323562	NM_001040142.2(SCN2A):c.4446+1A>G	Pathogenic
1342670	NM_001040142.2(SCN2A):c.1261T>G (p.Leu421Val)	Pathogenic
1342671	NM_001040142.2(SCN2A):c.4364T>A (p.Ile1455Asn)	Pathogenic

SpliceAI

4238 predictions. Top by Δscore:

Variant	Effect	Δscore
2:165296087:GAAA:G	donor_gain	1.0000
2:165296088:A:T	donor_gain	1.0000
2:165296091:G:GG	donor_gain	1.0000
2:165307837:C:CA	acceptor_gain	1.0000
2:165307859:T:G	acceptor_gain	1.0000
2:165307868:T:G	acceptor_gain	1.0000
2:165312087:GG:G	donor_gain	1.0000
2:165312088:GG:G	donor_gain	1.0000
2:165313619:GCCA:G	acceptor_gain	1.0000
2:165313896:TTGCA:T	acceptor_loss	1.0000
2:165313897:TGCA:T	acceptor_loss	1.0000
2:165313898:GCAGA:G	acceptor_loss	1.0000
2:165313899:CA:C	acceptor_loss	1.0000
2:165313900:A:AC	acceptor_loss	1.0000
2:165313900:A:AG	acceptor_gain	1.0000
2:165313901:G:GC	acceptor_gain	1.0000
2:165313901:GA:G	acceptor_gain	1.0000
2:165313901:GAC:G	acceptor_gain	1.0000
2:165313901:GACA:G	acceptor_gain	1.0000
2:165313901:GACAC:G	acceptor_gain	1.0000
2:165313993:T:TA	acceptor_gain	1.0000
2:165314105:TCAG:T	donor_loss	1.0000
2:165314106:CAG:C	donor_loss	1.0000
2:165314107:AG:A	donor_loss	1.0000
2:165314108:GG:G	donor_loss	1.0000
2:165314109:GT:G	donor_loss	1.0000
2:165314110:T:G	donor_loss	1.0000
2:165323153:T:G	acceptor_gain	1.0000
2:165323154:A:AG	acceptor_gain	1.0000
2:165323155:G:GG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005741 (2:165377563 G>A), RS1000026430 (2:165268028 A>G), RS1000076153 (2:165325519 G>A), RS1000084150 (2:165313222 C>T), RS1000098009 (2:165345784 C>T), RS1000139270 (2:165377562 T>G), RS1000142152 (2:165357422 C>A), RS1000161115 (2:165305047 A>G), RS1000177567 (2:165241179 T>C), RS1000189145 (2:165291418 C>T), RS1000191130 (2:165266791 G>T), RS1000192036 (2:165357469 A>G), RS1000205736 (2:165254545 G>A), RS1000225061 (2:165266488 T>G), RS1000232833 (2:165248134 A>C)

Disease associations

OMIM: gene MIM:182390 | disease phenotypes: MIM:607745, MIM:613721, MIM:618924, MIM:108600, MIM:601764, MIM:604233, MIM:606369, MIM:160120, MIM:616341, MIM:117100, MIM:308350, MIM:209850, MIM:613863, MIM:201300, MIM:616421, MIM:613722, MIM:128235, MIM:156200, MIM:617080, MIM:618468, MIM:616373

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 11	Definitive	Autosomal dominant
complex neurodevelopmental disorder	Definitive	Autosomal dominant
intellectual disability	Definitive	Autosomal dominant
seizures, benign familial infantile, 3	Strong	Autosomal dominant
episodic ataxia, type 9	Strong	Autosomal dominant
benign familial neonatal-infantile seizures	Supportive	Autosomal dominant
genetic developmental and epileptic encephalopathy	Supportive	Autosomal dominant
malignant migrating partial seizures of infancy	Supportive	Autosomal dominant
benign familial infantile epilepsy	Supportive	Autosomal dominant
Dravet syndrome	Supportive	Autosomal dominant
infantile spasms	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (40): seizures, benign familial infantile, 3 (MONDO:0011904), developmental and epileptic encephalopathy, 11 (MONDO:0013388), (MONDO:0100025), episodic ataxia, type 9 (MONDO:0030064), complex neurodevelopmental disorder (MONDO:0100038), spastic ataxia (MONDO:0017845), neurodevelopmental disorder (MONDO:0700092), benign familial infantile epilepsy (MONDO:0017615), developmental and epileptic encephalopathy (MONDO:0100620), pyridoxine-dependent epilepsy (MONDO:0009945), Dravet syndrome (MONDO:0100135), infantile spasms (MONDO:0018097), generalized epilepsy with febrile seizures plus (MONDO:0018214), Lennox-Gastaut syndrome (MONDO:0016532), autism spectrum disorder (MONDO:0005258)

Orphanet (21): Self-limited neonatal-infantile epilepsy (Orphanet:140927), Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Self-limited infantile epilepsy (Orphanet:306), Non-specific syndromic intellectual disability (Orphanet:528084), Spastic ataxia (Orphanet:316226), Pyridoxine-dependent-developmental and epileptic encephalopathy (Orphanet:3006), Dravet syndrome (Orphanet:33069), West syndrome (Orphanet:3451), Infantile epileptic spasms syndrome (Orphanet:697160), Genetic epilepsy with febrile seizure plus (Orphanet:36387), Lennox-Gastaut syndrome (Orphanet:2382), Hereditary episodic ataxia (Orphanet:211062), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Hereditary sensory and autonomic neuropathy type 2 (Orphanet:970), Epilepsy with myoclonic-atonic seizures (Orphanet:1942)

HPO phenotypes

208 total (30 of 208 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000297	Facial hypotonia
HP:0000340	Sloping forehead
HP:0000348	High forehead
HP:0000463	Anteverted nares
HP:0000466	Limited neck range of motion
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000657	Oculomotor apraxia
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000826	Precocious puberty
HP:0000961	Cyanosis
HP:0000975	Hyperhidrosis

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002129_12	Periodontitis (DPAL)	5.000000e-06
GCST002672_4	Febrile seizures	3.000000e-10
GCST002673_3	Febrile seizures (MMR vaccine-unrelated)	2.000000e-07
GCST002674_5	Febrile seizures (MMR vaccine-related)	4.000000e-06
GCST006630_51	Diastolic blood pressure	3.000000e-10
GCST007343_2	Epilepsy	2.000000e-13
GCST007352_1	Focal epilepsy	7.000000e-09
GCST007353_3	Generalized epilepsy	5.000000e-08
GCST007401_10	Factor VII activity	8.000000e-07
GCST008103_11	Bipolar disorder	2.000000e-09
GCST008154_50	Trunk fat mass	3.000000e-06
GCST008647_39	Urinary sodium excretion	1.000000e-10
GCST010002_403	Refractive error	1.000000e-11
GCST010988_192	Adult body size	2.000000e-08
GCST011102_2	Bipolar disorder	2.000000e-09
GCST012465_47	Bipolar disorder	3.000000e-08
GCST90000047_75	Age at first sexual intercourse	1.000000e-08
GCST90000050_17	Age at first birth	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006519	MMR-related febrile seizures
EFO:0006336	diastolic blood pressure
EFO:0004619	factor VII measurement
EFO:0009282	sodium measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0009101	age at first birth measurement

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D004828	Epilepsies, Partial	C10.228.140.490.360
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D009069	Movement Disorders	C10.228.662
D065886	Neurodevelopmental Disorders	F03.625
C538001	Dystonia 12 (supp.)
C567827	Generalized Epilepsy With Febrile Seizures Plus, 7 (supp.)
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)
C536254	Pyridoxine-dependent epilepsy (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096682 (PROTEIN FAMILY), CHEMBL2331043 (PROTEIN FAMILY), CHEMBL4187 (SINGLE PROTEIN), CHEMBL4523672 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

99 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 507,182 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1093	ARTICAINE	4	6,583
CHEMBL1098	BUPIVACAINE	4	37,899
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL1193	PHENIRAMINE	4	11,218
CHEMBL1194	PRILOCAINE	4	15,137
CHEMBL1195	PROPOXYCAINE	4	5,653
CHEMBL1196	PROPARACAINE	4	12,973
CHEMBL1197	HEXYLCAINE	4	4,372
CHEMBL1198	PRAMOXINE	4	10,295
CHEMBL1200	BENOXINATE	4	6,712
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL1480	FELODIPINE	4	30,761
CHEMBL16	PHENYTOIN	4	53,375
CHEMBL170	QUININE	4	108,216
CHEMBL1726	NISOLDIPINE	4	18,921
CHEMBL193	NIFEDIPINE	4
CHEMBL2	PRAZOSIN	4
CHEMBL23	DILTIAZEM	4
CHEMBL24072	PRENYLAMINE	4
CHEMBL370805	COCAINE	4
CHEMBL422	TRIFLUOPERAZINE	4
CHEMBL43064	CINNARIZINE	4
CHEMBL479	THIORIDAZINE	4
CHEMBL492	ETIDOCAINE	4
CHEMBL505	CHLORPHENIRAMINE	4

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

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17183814	Efficacy	4	antiepileptics;carbamazepine;phenobarbital;phenytoin;valproic acid	Epilepsy
rs2304016	Efficacy	3	antiepileptics	Epilepsy
rs2304016	Efficacy	3	carbamazepine	Epilepsy
rs2304016	Efficacy	3	lamotrigine	Epilepsy
rs2304016	Efficacy	3	oxcarbazepine	Epilepsy
rs2304016	Efficacy	3	phenytoin	Epilepsy
rs2304016	Efficacy	3	topiramate	Epilepsy

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2304016	SCN2A	3	3.25	6	oxcarbazepine;antiepileptics;carbamazepine;lamotrigine;phenytoin;topiramate
rs17183814	SCN2A	4	-2.50	1	antiepileptics;carbamazepine;phenobarbital;phenytoin;valproic acid

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Voltage-gated sodium channels (Na_V)

Most potent curated ligand interactions (25 total), top 25:

Ligand	Action	Affinity	Parameter
β-scorpion toxin Css IV	Partial agonist	9.7	pKd
batrachotoxin	Agonist	9.1	pKd
μ-conotoxin SmIIIA	Pore blocker	8.9	pKd
saxitoxin	Pore blocker	8.8	pIC50
α-scorpion toxin 2	Slows inactivation	8.7	pKd
GNE-131	Inhibition	8.15	pIC50
ATX-II	Slows inactivation	8.1	pEC50
tetrodotoxin	Pore blocker	8.0	pIC50
XPC-5462	Channel blocker	7.96	pIC50
GNE-616	Inhibition	7.92	pKd
huwentoxin IV	Voltage-dependent inhibition	7.8	pKd
protoxin II	Voltage-dependent inhibition	7.4	pKi
relutrigine	Inhibition	6.76	pIC50
funapide	Inhibition	6.22	pIC50
etidocaine	Pore blocker	6.0	pIC50
aconitine	Partial agonist	5.9	pKd
Bc-III	Slows inactivation	5.8	pEC50
AFT-II	Slows inactivation	5.7	pEC50
cannabidiol	Channel blocker	5.54	pIC50
veratridine	Partial agonist	5.2	pKd
lidocaine	Pore blocker	5.0	pIC50
phenytoin	Pore blocker	4.9	pIC50
lacosamide	Antagonist	4.52	pIC50
lamotrigine	Pore blocker	4.5	pIC50
δ-hexatoxin-Mg1a	Slows inactivation	4.5	pEC50

Binding affinities (BindingDB)

577 measured of 587 human assays (587 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-cyclopropyl-4-[(3R)-1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	0.3 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]piperidin-4-yl]methoxy]-2-fluorobenzamide	IC50	0.8 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[[3-chloro-5-(trifluoromethoxy)phenyl]methyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1.3 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(2S)-2-(3,5-dichlorophenyl)-1-methoxypropan-2-yl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichloro-2-fluorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[1-(2-chloro-4-fluorophenyl)-2,2,2-trifluoroethyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1.6 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[(2-chlorophenyl)methyl]piperidin-3-yl]oxy-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[(3R)-1-[(2,4-dichlorophenyl)methyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1R)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[2-(3,5-dichlorophenyl)propan-2-yl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]-4-methylpiperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.7 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.8 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-2-fluoro-4-[(3R)-1-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]oxy-N-methylsulfonylbenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[(3R)-1-[(1S)-1-(3,5-dichlorophenyl)ethyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[[3-chloro-5-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[2-(3,5-dichlorophenyl)propan-2-yl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[1-(3,5-dichlorophenyl)-2,2,2-trifluoroethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
N-(azetidin-1-ylsulfonyl)-4-[(3R,6R)-1-[(2-chloro-4-fluorophenyl)methyl]-6-methylpiperidin-3-yl]oxy-5-cyclopropyl-2-fluorobenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R,6R)-1-[(2-chloro-4-fluorophenyl)methyl]-6-methylpiperidin-3-yl]oxy-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	1.9 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[1-(3,5-dichlorophenyl)propyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	2 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[bis(3-chlorophenyl)methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[bis(2-chlorophenyl)methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[(3R)-1-(3,5-dichlorophenyl)piperidin-3-yl]oxy-2-fluorobenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[[2,5-bis(trifluoromethyl)phenyl]methyl]-4-methylpiperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[[3-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[bis(4-chlorophenyl)methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[(3R)-1-[(2,4-dimethylphenyl)methyl]piperidin-3-yl]oxy-2-fluoro-N-methylsulfonylbenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[5-chloro-4-(trifluoromethyl)-2-pyridinyl]-4-methylpiperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.1 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1S)-1-(2,4-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	2.2 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[(3,5-dichlorophenyl)methyl]piperidin-4-yl]methoxy]-2-fluorobenzamide	IC50	2.2 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[(2-chloro-4-fluorophenyl)methyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.2 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[(1R,5S)-3-[3-chloro-5-(trifluoromethoxy)phenoxy]-8-azabicyclo[3.2.1]octan-8-yl]methyl]-5-cyclopropyl-N-cyclopropylsulfonyl-2-fluorobenzamide	IC50	2.2 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[4-(3,5-dichlorophenyl)sulfanylpiperidin-1-yl]methyl]-2-fluorobenzamide	IC50	2.2 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)-2-methoxyethyl]piperidin-4-yl]methoxy]-2-fluorobenzamide	IC50	2.3 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[(1S)-1-(2-chloro-4-fluorophenyl)ethyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.3 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[(1S)-1-(5-chloro-6-cyclopropyl-2-pyridinyl)ethyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.3 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[2-(3-chlorophenyl)propan-2-yl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluorobenzamide	IC50	2.3 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-2-fluoro-4-[(3R)-1-[[4-fluoro-2-(trifluoromethyl)phenyl]methyl]piperidin-3-yl]oxybenzamide	IC50	2.4 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[[1-[[5-chloro-2-(trifluoromethyl)phenyl]methyl]-4-methylpiperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.4 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1R)-1-(3,5-dichlorophenyl)propyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	2.4 nM	US-9694002: Substituted benzamides and methods of use thereof
N-(azetidin-1-ylsulfonyl)-4-[(3R,6S)-1-[(2-chloro-4-fluorophenyl)methyl]-6-methylpiperidin-3-yl]oxy-5-cyclopropyl-2-fluorobenzamide	IC50	2.4 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]-3-methylazetidin-3-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	2.4 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluorobenzamide	IC50	2.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(1R)-1-(3,5-dichlorophenyl)-2-methoxy-2-methylpropyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	IC50	2.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-4-[[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]methoxy]-N-ethylsulfonyl-2-fluorobenzamide	IC50	2.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[[1-[(3,5-dichlorophenyl)-phenylmethyl]-3-methylazetidin-3-yl]methoxy]-2-fluorobenzamide	IC50	2.5 nM	US-9694002: Substituted benzamides and methods of use thereof
4-[(3R)-1-[(2-chloro-4-methylphenyl)methyl]piperidin-3-yl]oxy-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	IC50	2.5 nM	US-9694002: Substituted benzamides and methods of use thereof
5-cyclopropyl-N-cyclopropylsulfonyl-4-[(3R)-1-[(3,5-dichlorophenyl)methyl]piperidin-3-yl]oxy-2-fluorobenzamide	IC50	2.6 nM	US-9694002: Substituted benzamides and methods of use thereof

ChEMBL bioactivities

261 potent at pChembl≥5 of 343 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL3617063
9.55	IC50	0.28	nM	CHEMBL4060338
9.35	IC50	0.45	nM	CHEMBL4060338
9.00	IC50	1	nM	SAXITOXIN
8.70	IC50	2	nM	CHEMBL4070670
8.70	IC50	2	nM	CHEMBL3662190
8.68	IC50	2.1	nM	CHEMBL4070670
8.60	IC50	2.519	nM	CHEMBL4217988
8.52	IC50	3	nM	CHEMBL4217988
8.38	IC50	4.2	nM	CHEMBL3341983
8.28	EC50	5.3	nM	CHEMBL4064160
8.22	IC50	6	nM	CHEMBL3662077
8.15	IC50	7	nM	CHEMBL4290579
8.12	IC50	7.5	nM	CHEMBL4082248
8.00	IC50	10	nM	CHEMBL4285790
7.92	EC50	12	nM	CHEMBL4060338
7.92	Kd	12	nM	CHEMBL4464990
7.92	IC50	12	nM	CHEMBL4854735
7.89	IC50	13	nM	CHEMBL4580996
7.85	IC50	14	nM	CHEMBL4279238
7.85	IC50	14	nM	TETRODOTOXIN
7.82	IC50	15.02	nM	BREVETOXIN B
7.82	IC50	15	nM	CHEMBL6143914
7.72	IC50	18.9	nM	CHEMBL3657855
7.70	IC50	20	nM	CHEMBL3657855
7.58	IC50	26	nM	CHEMBL4064160
7.54	IC50	29	nM	CHEMBL4068937
7.51	IC50	31	nM	CHEMBL4460028
7.46	IC50	35	nM	CHEMBL4082248
7.42	IC50	38	nM	CHEMBL5094715
7.39	IC50	41	nM	CHEMBL4224739
7.33	IC50	47	nM	CHEMBL4466858
7.30	IC50	50	nM	CHEMBL1269990
7.27	IC50	54	nM	PIMOZIDE
7.19	Kd	64	nM	CHEMBL4444707
7.19	IC50	65	nM	CHEMBL5598329
7.18	IC50	66	nM	CHEMBL4435054
7.16	IC50	70	nM	CHEMBL1270301
7.10	EC50	79	nM	CHEMBL4082248
7.10	IC50	79	nM	CHEMBL3318132
7.00	IC50	100	nM	CHEMBL486495
6.96	IC50	110	nM	PF-05089771
6.96	IC50	110	nM	CHEMBL1269882
6.92	EC50	120	nM	CHEMBL4070670
6.92	IC50	119	nM	PF-05089771
6.92	IC50	120	nM	CHEMBL4588728
6.92	IC50	120	nM	CHEMBL5598304
6.92	IC50	120	nM	CHEMBL1269991
6.90	IC50	125	nM	CHEMBL4471825
6.85	Kd	140	nM	CHEMBL4471012

PubChem BioAssay actives

259 with measured affinity, of 897 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(3R,5S,6S,11R,12S,16S)-14,17-diamino-19,19-dihydroxy-6-(hydroxymethyl)-10-oxo-3-sulfooxy-8-oxa-1,9,13,15,18-pentazapentacyclo[9.5.2.13,16.05,9.012,16]nonadeca-14,17-dien-13-yl]methyl N-hydroxycarbamate	1246042: Inhibition of NaV1.2 channel (unknown origin) expressed in Xenopus laevis oocytes by two-electrode oocyte voltage-clamp method	ic50	<0.0001	uM
4-[2-(2-amino-3H-benzimidazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1300004: Inhibition of full length human Nav1.2 channel expressed in HEK cells co-expressing human sodium channel subunit beta1 at holding potential -35 mV by automated voltage clamp analysis	ic50	0.0002	uM
(5R,7R)-7-decyl-1-oxa-8,10-diazaspiro[4.5]dec-8-en-9-amine	1432176: Antagonist activity at human Nav1.2 expressed in HEK293T cells assessed as inhibition of VTD-induced tail current by whole cell patch clamp method relative to control	ic50	0.0003	uM
[(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-4-yl]methyl carbamate	1525389: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay	ic50	0.0010	uM
(5S,7S)-7-decyl-1-oxa-8,10-diazaspiro[4.5]dec-8-en-9-amine	1432176: Antagonist activity at human Nav1.2 expressed in HEK293T cells assessed as inhibition of VTD-induced tail current by whole cell patch clamp method relative to control	ic50	0.0020	uM
5-cyclopropyl-N-cyclopropylsulfonyl-2-fluoro-4-[(6-methylspiro[2.5]octan-6-yl)methoxy]benzamide	1525389: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay	ic50	0.0020	uM
3-cyano-4-[2-[2-[(2-piperidin-4-ylethylamino)methyl]-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1365875: Inhibition of human Nav1.2 expressed in HEK cells by patch clamp electrophysiology method	ic50	0.0025	uM
4-[2-(3-amino-1,2-benzoxazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1300004: Inhibition of full length human Nav1.2 channel expressed in HEK cells co-expressing human sodium channel subunit beta1 at holding potential -35 mV by automated voltage clamp analysis	ic50	0.0042	uM
(5R,6S,7R)-9-amino-7-decyl-1-oxa-8,10-diazaspiro[4.5]dec-8-ene-6-carboxylic acid	1432177: Inhibition of Nav1.2 (unknown origin) by cell based assay	ec50	0.0053	uM
5-cyclopropyl-N-cyclopropylsulfonyl-4-[(4,4-difluoro-1-methylcyclohexyl)methoxy]-2-fluorobenzamide	1960144: Inhibition of human Nav1.2 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -35 mV holding potential by PatchXpress automated voltage clamp electrophysiology technique	ic50	0.0060	uM
N-[7-(1-adamantylmethoxy)-6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl]cyclopropanesulfonamide	1410604: Inhibition of inactivated state of recombinant human NaV1.2 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -35 mV holding potential by PX automated voltage clamp method	ic50	0.0070	uM
(5S,6R,7S)-9-amino-7-decyl-1-oxa-8,10-diazaspiro[4.5]dec-8-ene-6-carboxylic acid	1432157: Antagonist activity at human Nav1.2 expressed in HEK293T cells assessed as inhibition of VTD-induced sustained current by whole cell patch clamp method relative to control	ic50	0.0075	uM
N-[6-cyclopropyl-7-[(3,5-dichlorophenoxy)methyl]-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanesulfonamide	1410604: Inhibition of inactivated state of recombinant human NaV1.2 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -35 mV holding potential by PX automated voltage clamp method	ic50	0.0100	uM
(4S)-6-fluoro-4-[(2R,4S)-2-pyridin-2-yl-4-(trifluoromethyl)piperidin-1-yl]-N-pyrimidin-4-yl-3,4-dihydro-2H-chromene-7-sulfonamide	1587753: Inhibition of full length human Nav1.2 expressed in HEK293 cells at -60 mV holding potential by manual patch clamp electrophysiology method	kd	0.0120	uM
4-[(3S,4S)-3-(3,4-difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-4-yl]oxy-3,5-difluoro-N-(6-fluoro-2-pyridinyl)benzenesulfonamide	1754511: Inhibition of human Nav1.2 by V1/2 protocol based analysis	ic50	0.0120	uM
5-chloro-4-[[(1S)-1-(2,5-difluorophenyl)ethyl]amino]-2-fluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1616312: Inhibition of recombinant human full length Nav1.2 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay	ic50	0.0130	uM
(1R,5R,6R,7R,9S,11S,12S,13S,14S)-3-amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol	1525389: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay	ic50	0.0140	uM
N-[7-(1-adamantylmethoxy)-6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanesulfonamide	1410604: Inhibition of inactivated state of recombinant human NaV1.2 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -35 mV holding potential by PX automated voltage clamp method	ic50	0.0140	uM
2-[[(1R,3S,5R,7S,9R,11S,12S,14R,16R,18S,20R,21Z,24S,26R,28S,30R,31R,33S,35R,37S,42R,44S,46R,48S)-12-hydroxy-1,3,11,24,31,41,44-heptamethyl-39-oxo-2,6,10,15,19,25,29,34,38,43,47-undecaoxaundecacyclo[26.22.0.03,26.05,24.07,20.09,18.011,16.030,48.033,46.035,44.037,42]pentaconta-21,40-dien-14-yl]methyl]prop-2-enal	254847: Inhibitory concentration against synaptosome using [3H]PbTx-3	ic50	0.0150	uM
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide	1831648: Inhibition of full length human Nav1.2 expressed in HEK cells by whole cell voltage clamp analysis	ic50	0.0189	uM
2-oxo-3-[(1R)-1-(1,2,3,4-tetrahydroisoquinolin-8-yl)ethyl]-N-(1,2,4-thiadiazol-5-yl)-1,3-benzoxazole-6-sulfonamide	1466785: Inhibition of Nav1.2 (unknown origin)	ic50	0.0290	uM
4-[[2-[(2,2-dimethylazetidin-1-yl)methyl]-6-fluorophenyl]methylamino]-2,6-difluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1616312: Inhibition of recombinant human full length Nav1.2 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay	ic50	0.0310	uM
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831648: Inhibition of full length human Nav1.2 expressed in HEK cells by whole cell voltage clamp analysis	ic50	0.0380	uM
(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S,54S,57S,60R,65R,68S,71S,74S)-27,57-bis(4-aminobutyl)-21-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-24-(3-amino-3-oxopropyl)-54,74-bis(3-carbamimidamidopropyl)-13,51-bis(2-carboxyethyl)-45-(carboxymethyl)-39-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-30,36,68-tris(1H-indol-3-ylmethyl)-71-(2-methylpropyl)-7,33-bis(2-methylsulfanylethyl)-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,81-tricosaoxo-4-propan-2-yl-18,19,62,63,78,79-hexathia-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,82-tricosazatricyclo[40.34.4.216,60]dooctacontane-65-carbonyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1388447: Inhibition of Nav1.2 (unknown origin) expressed in xenopus oocytes at -80 mV holding potential by two-electrode voltage-clamp method	ic50	0.0410	uM
2,6-difluoro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]-N-(1,3-thiazol-4-yl)benzenesulfonamide	1616312: Inhibition of recombinant human full length Nav1.2 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay	ic50	0.0470	uM
5-(4-chlorophenyl)-N-[(2-piperidin-1-ylphenyl)methyl]pyridine-3-carboxamide	527217: Inhibition of human NaV1.2 by electrophysiology	ic50	0.0500	uM
Pimozide	1207165: Inhibition of Na channel (species unknown)	ic50	0.0540	uM
4-[[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1525419: Binding affinity to human recombinant Nav1.2 by radioligand binding assay	kd	0.0640	uM
4-(3-methoxyphenyl)-6-(8-methyl-1,3,4,5-tetrahydro-2-benzazepin-2-yl)pyrimidin-2-amine	2120760: Inhibition of human Nav1.2 expressed in HEK293 cells at -40 mv holding potential measured after 5 mins by whole cell voltage clamp electrophysiological analysis	ic50	0.0650	uM
2,6-difluoro-4-[[2-fluoro-6-[[methyl(propan-2-yl)amino]methyl]phenyl]methylamino]-N-(1,3-thiazol-4-yl)benzenesulfonamide	1616312: Inhibition of recombinant human full length Nav1.2 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay	ic50	0.0660	uM
5-(4-chlorophenyl)-N-[(2-piperidin-1-yl-3-pyridinyl)methyl]pyridine-3-carboxamide	527217: Inhibition of human NaV1.2 by electrophysiology	ic50	0.0700	uM
[5-(4-tert-butylphenyl)furan-2-yl]-(4-cyclohexylpiperazin-1-yl)methanone	404535: Inhibition of human recombinant Nav1.2 channel expressed in HEK293 cells by whole cell voltage clamp technique	ic50	0.1000	uM
4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1525389: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay	ic50	0.1100	uM
5-(4-chlorophenyl)-N-[(2-methylphenyl)methyl]pyridine-3-carboxamide	527217: Inhibition of human NaV1.2 by electrophysiology	ic50	0.1100	uM
(3S)-3-amino-4-oxo-4-[[(1R,4S,7S,10S,13S,16S,19R,24R,27S,30S,33S,36S,39S,42S,45R,51S,54S,57S,60R,65R,68S,71S,74S,77S,83S)-7,30,36,42,57-pentakis(4-aminobutyl)-77-benzyl-39,68-bis(3-carbamimidamidopropyl)-24-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-4,13-bis(2-carboxyethyl)-10,16,83-tris(carboxymethyl)-27,71-bis[(4-hydroxyphenyl)methyl]-54-(1H-imidazol-5-ylmethyl)-51-(2-methylpropyl)-33,74-bis(2-methylsulfanylethyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,78,81,84,91-hexacosaoxo-21,22,62,63,87,88-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,79,82,85,90-hexacosazatricyclo[43.40.4.219,60]hennonacontan-65-yl]amino]butanoic acid	1525389: Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay	ic50	0.1200	uM
4-(3-methoxyphenyl)-6-(1,3,4,5-tetrahydro-2-benzazepin-2-yl)pyrimidin-2-amine	2120760: Inhibition of human Nav1.2 expressed in HEK293 cells at -40 mv holding potential measured after 5 mins by whole cell voltage clamp electrophysiological analysis	ic50	0.1200	uM
5-(4-chlorophenyl)-N-[(2-morpholin-4-ylphenyl)methyl]pyridine-3-carboxamide	527217: Inhibition of human NaV1.2 by electrophysiology	ic50	0.1200	uM
4-[[2-[[tert-butyl(methyl)amino]methyl]-6-fluorophenyl]methylamino]-2,6-difluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1616312: Inhibition of recombinant human full length Nav1.2 co-expressed with human SCN1B in HEK293 cells measured after 20 mins at -45 mV holding potential by whole cell patch clamp assay	ic50	0.1250	uM
N-cyclopropylsulfonyl-1-[(3R)-1-[(1R)-1-(3,5-dichlorophenyl)ethyl]pyrrolidin-3-yl]-6-fluoro-3-methylindazole-5-carboxamide	1525419: Binding affinity to human recombinant Nav1.2 by radioligand binding assay	kd	0.1400	uM
4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1457691: Inhibition of human NaV1.2 expressed in HEK cells assessed as half inactivation potential at -120 mV holding potential by automated patch clamp method	ic50	0.1490	uM
2,6-ditert-butyl-4-[[3-(2,6-dimethylphenoxy)propylamino]methyl]phenol	2120835: Inhibition of Nav1.2 (unknown origin)	ic50	0.1800	uM
2,5-bis[3-(trifluoromethyl)phenyl]-1H-imidazole	351546: Inhibition of human Nav1.2 channel expressed in HEK cells by patch-clamp electrophysiology method	ic50	0.2000	uM
2,2-diphenyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]acetamide	1246060: Inhibition of human NaV1.2 channel by patch clamp electrophysiology assay	ic50	0.2400	uM
Loperamide	205267: Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex	ic50	0.2700	uM
4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1457691: Inhibition of human NaV1.2 expressed in HEK cells assessed as half inactivation potential at -120 mV holding potential by automated patch clamp method	ic50	0.2760	uM
4-[4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide	205267: Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex	ic50	0.2800	uM
3,3-diphenyl-N-(1-phenylpropan-2-yl)propan-1-amine	205267: Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex	ic50	0.3000	uM
[5-(4-chlorophenyl)furan-2-yl]-(4-cyclohexylpiperazin-1-yl)methanone	404535: Inhibition of human recombinant Nav1.2 channel expressed in HEK293 cells by whole cell voltage clamp technique	ic50	0.3500	uM
N-(3,5-dimethylphenyl)-6-(4-ethoxyphenyl)pyrazine-2-carboxamide	536195: Inhibition of human recombinant NaV1.2 by electrophysiology	ic50	0.3600	uM
5-chloro-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide	1457691: Inhibition of human NaV1.2 expressed in HEK cells assessed as half inactivation potential at -120 mV holding potential by automated patch clamp method	ic50	0.3980	uM

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Ascorbic Acid	affects cotreatment, increases expression, affects binding	2
Benzo(a)pyrene	increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	affects binding, increases reaction, affects reaction, affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
decamethrin	decreases expression, decreases reaction	1
sodium arsenite	affects methylation	1
beta-methylcholine	affects expression	1
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases expression, decreases reaction	1
4-methoxycinnamate methyl ester	increases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
PD 150606	decreases expression, decreases reaction	1
1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene	increases expression, affects cotreatment	1
pinostrobin	increases phosphorylation	1
Chir 99021	affects binding, affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
XAV939	increases expression, affects binding, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Lamotrigine	decreases activity	1
Arsenic Trioxide	increases expression	1
Cyclic AMP	increases expression, affects cotreatment	1
Atrazine	decreases expression	1

ChEMBL screening assays

203 unique, capped per target: 172 binding, 20 functional, 10 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL679768	Binding	Inhibition of [3H]BTX binding to guinea pig voltage-dependent sodium channel	Anticonvulsant activity of piperidinol and (dialkylamino)alkanol esters. — J Med Chem
CHEMBL749469	Functional	Antagonism of batrachotoxin-mediated sodium ion uptake into cultured neuroblastoma cells	Batrachotoxin binding site antagonists — Bioorg Med Chem Lett
CHEMBL3883160	ADMET	Inhibition of human Nav1.2 expressed in CHO cells assessed as reduction in peak frequency currents by whole-cell voltage-clamp method	Fused heterocyclic compounds as ion channel modulators

Cellosaurus cell lines

7 cell lines: 5 induced pluripotent stem cell, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0Y9	B’SYS CHO Nav1.2	Spontaneously immortalized cell line	Female
CVCL_C8H7	FINi001-A	Induced pluripotent stem cell	Female
CVCL_C8SP	FINi003-A	Induced pluripotent stem cell	Male
CVCL_E4Q2	KOLF2.1J SCN2A 94.3kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_LC66	PrecisION hNav1.2-CHO	Spontaneously immortalized cell line	Female
CVCL_VE79	PFIZi031-A	Induced pluripotent stem cell	Male
CVCL_WN05	CBTCi008-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06598449	PHASE4	RECRUITING	Assessment of Safety of the Use of Fenfluramine in Children With Dravet Syndrome Under 24 Months of Age
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT07112365	PHASE4	NOT_YET_RECRUITING	The FINTEPLA as an Anti-SUDEP Therapy in Dravet Syndrome Project
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT00098475	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
NCT00114101	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
NCT00644228	PHASE3	ACTIVE_NOT_RECRUITING	Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma
NCT00869206	PHASE3	COMPLETED	Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement
NCT02091375	PHASE3	COMPLETED	Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1)
NCT02174094	PHASE3	WITHDRAWN	Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
NCT02187809	PHASE3	TERMINATED	Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
NCT02224573	PHASE3	COMPLETED	An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
NCT02224703	PHASE3	COMPLETED	GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome
NCT02318563	PHASE3	WITHDRAWN	Cannabidiol Oral Solution as an Adjunctive Therapy for Treatment of Participants With Inadequately Controlled Dravet Syndrome
NCT02682927	PHASE3	COMPLETED	A Trial of Two Fixed Doses of ZX008 (Fenfluramine HCl) in Children and Young Adults With Dravet Syndrome
NCT02823145	PHASE3	COMPLETED	An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution in Children and Young Adults With Dravet Syndrome
NCT02926898	PHASE3	COMPLETED	A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome
NCT03299842	PHASE3	TERMINATED	A Study to Assess the Usability of the Embrace Seizure Detection Watch in Children and Young Adults With Dravet Syndrome