SCN1A

Summary

SCN1A (sodium voltage-gated channel alpha subunit 1, HGNC:10585) is a protein-coding gene on chromosome 2q24.3, encoding Sodium channel protein type 1 subunit alpha (P35498). Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. It is haploinsufficient (ClinGen: sufficient evidence).

Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5’ untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript.

Source: NCBI Gene 6323 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 12
• Clinical variants (ClinVar): 2,848 total — 889 pathogenic, 315 likely-pathogenic
• Phenotypes (HPO): 228
• Druggable target: yes — 94 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001165963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10585
Approved symbol	SCN1A
Name	sodium voltage-gated channel alpha subunit 1
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Nav1.1, GEFSP2, HBSCI, NAC1, SMEI
Ensembl gene	ENSG00000144285
Ensembl biotype	protein_coding
OMIM	182389
Entrez	6323

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 12 protein_coding, 6 retained_intron, 6 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay

ENST00000303395, ENST00000375405, ENST00000409050, ENST00000473295, ENST00000491429, ENST00000507401, ENST00000625916, ENST00000635750, ENST00000635776, ENST00000635893, ENST00000636194, ENST00000636759, ENST00000637038, ENST00000637285, ENST00000637968, ENST00000637988, ENST00000640036, ENST00000641575, ENST00000641603, ENST00000641996, ENST00000642141, ENST00000671940, ENST00000673490, ENST00000674923, ENST00000689288, ENST00000713692, ENST00000714447, ENST00000714448, ENST00000714449, ENST00000714450

RefSeq mRNA: 15 — MANE Select: NM_001165963 NM_001165963, NM_001165964, NM_001202435, NM_001353948, NM_001353949, NM_001353950, NM_001353951, NM_001353952, NM_001353954, NM_001353955, NM_001353957, NM_001353958, NM_001353960, NM_001353961, NM_006920

CCDS: CCDS33316, CCDS54413, CCDS54414, CCDS86891

Canonical transcript exons

ENST00000674923 — 29 exons

Exon	Start	End
ENSE00001128577	166013744	166013898
ENSE00001128607	166048886	166048949
ENSE00001128613	166051719	166051988
ENSE00001128657	166002472	166002753
ENSE00001128727	166043669	166044049
ENSE00001129686	166036048	166036530
ENSE00001286304	166054638	166054766
ENSE00001286382	166015607	166015727
ENSE00001286421	166041231	166041469
ENSE00001286444	166045043	166045327
ENSE00001785173	166056411	166056500
ENSE00002033907	166127771	166128020
ENSE00002040027	166077710	166077801
ENSE00002435591	166046770	166046976
ENSE00002441017	166052852	166052943
ENSE00002456352	166009719	166009841
ENSE00002467709	165994146	165994416
ENSE00002470479	166058570	166058688
ENSE00002471334	166047627	166047768
ENSE00002471795	166037776	166038132
ENSE00002481769	165996013	165996117
ENSE00002512505	166012109	166012282
ENSE00002513670	166039423	166039596
ENSE00002516503	166042292	166042424
ENSE00003585067	165998038	165998175
ENSE00003654618	165999723	165999776
ENSE00003761695	166073358	166073670
ENSE00003792641	166126924	166127010
ENSE00004020733	165985813	165992422

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 97.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.1766 / max 1119.5819, expressed in 162 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31680	2.5333	147
31683	1.0297	83
31679	0.2593	92
31681	0.1636	72
31682	0.1301	49
31684	0.0442	29
31677	0.0165	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	97.81	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.97	gold quality
primary visual cortex	UBERON:0002436	95.39	gold quality
pons	UBERON:0000988	95.27	gold quality
right uterine tube	UBERON:0001302	95.20	gold quality
occipital lobe	UBERON:0002021	93.70	gold quality
endothelial cell	CL:0000115	93.41	gold quality
cerebellar vermis	UBERON:0004720	92.57	gold quality
superior vestibular nucleus	UBERON:0007227	92.47	gold quality
parietal lobe	UBERON:0001872	92.12	gold quality
postcentral gyrus	UBERON:0002581	92.06	gold quality
superior frontal gyrus	UBERON:0002661	91.16	gold quality
middle temporal gyrus	UBERON:0002771	89.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.29	gold quality
prefrontal cortex	UBERON:0000451	87.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.89	gold quality
frontal cortex	UBERON:0001870	86.64	gold quality
orbitofrontal cortex	UBERON:0004167	86.47	gold quality
medulla oblongata	UBERON:0001896	85.79	gold quality
neocortex	UBERON:0001950	85.45	gold quality
CA1 field of hippocampus	UBERON:0003881	85.03	gold quality
lateral globus pallidus	UBERON:0002476	84.69	gold quality
cerebral cortex	UBERON:0000956	84.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.27	gold quality
buccal mucosa cell	CL:0002336	83.61	gold quality
right frontal lobe	UBERON:0002810	83.14	gold quality
medial globus pallidus	UBERON:0002477	82.73	gold quality
telencephalon	UBERON:0001893	82.36	gold quality
globus pallidus	UBERON:0001875	82.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	66.77
E-ANND-3	yes	11.19
E-CURD-11	no	187.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ESR1, ESR2, IL10, RCOR2, TNF, ZNF91

miRNA regulators (miRDB)

184 targeting SCN1A, 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-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Three novel frameshift and seven nonsense mutations in the SCN1A gene have been identified in 14 Japanese patients with severe myoclonic epilepsy in infancy. (PMID:11940708)
• Significant correlation of the SCN1A mutations and severe myoclonic epilepsy in infancy (PMID:12083760)
• The effects of three mutations in SCN1A have been characterized in cultured mammalian cells as a gain-of-function abnormality causing prolonged membrane depolarization, a plausible underlying biophysical mechanism responsible for inherited epilepsy. (PMID:12086636)
• R542Q in SCN1A was observed in one autism family and had previously been identified in a patient with juvenile myoclonic epilepsy (PMID:12610651)
• the SCN1A gene might not be one of the susceptibility factors for febrile convulsions (PMID:12742596)
• de novo mutations in SCN1A are a major cause of isolated severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) (PMID:12754708)
• familial severe myoclonic epilepsy of infancy is geneticlly heterogenous for SCN1A (Nav1.1)mutation (PMID:12773292)
• SCN1A channels bearing myoclonic epilepsy (SMEI) nonsense and missense mutations show attenuated or barely detectable inward sodium currents, indicating that SMEI mutations lead to loss-of-function and may contribute to development of SMEI phenotypes. (PMID:12837571)
• Missense mutations in the SCN1A gene are major causes of generalized epilepsy with febrile seizures plus (GEFS+). (PMID:12919402)
• Typical Severe Myoclonic Epilepsy (SME) and Borderline SME show distinct differences in photoparoxysmal response and gender, which might be caused by some genetic mechanism(s) other than the SCN1A gene mutation. (PMID:13129592)
• 8 SCN1A mutations from severe myoclonic epilepsy of infancy and 1 from West syndrome were characterized and their effect on the structure and function of the protein are discussed. (PMID:14504318)
• The sodium channel function of SCN1A with misesense mutations is dysfunctional in familial epilepsy. (PMID:14672992)
• In both core severe myoclonic epilepsy in infancy and severe borderline myoclonic epilepsy, various mutations of SCN1A including nonsense and missense mutations were identified (PMID:14738421)
• The clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy. (PMID:15087100)
• 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)
• Mutations in SCN1A are associated with severe myoclonic epilepsy. (PMID:15263074)
• Mutations in the pore regions may produce more severe channel dysfunction, including activation/inactivation dysfunction or abnormal voltage dependency, than those in other transmembrane regions, resulting in a more severe epilepsy phenotype. (PMID:15277629)
• In janese corhort study showed variuos phenotypic manifestions of Dravet syndrom in releation of SCN1A mutation. (PMID:15508916)
• The D1866Y mutation in SCN1A weakens the interaction between the C-terminal domains of the alpha and beta1 subunits, demonstrating a novel molecular mechanism leading to seizure susceptibility. (PMID:15525788)
• A base substitution 5569G–>T of voltage-gated sodium channel alpha-1 subunit gene was found in DNA derived from the affected members of this family. (PMID:15715999)
• epilepsy related mutations (PMID:15880351)
• heterozygous missense mutation (Gln1489Lys) in the neuronal voltage-gated sodium channel gene SCN1A can cause familial hemiplegic migraine (PMID:16054936)
• SCN1A mutations associated with ICEGTC (intractable childhood epilepsy with generalized tonic-clonic seizures) result in a wide spectrum of biophysical defects, including gating impairments, shifted voltage dependence and reduced use dependence. (PMID:16210358)
• Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures. (PMID:16326807)
• Our findings define single-channel properties for WT-SCN1A, detail the functional phenotypes for two human epilepsy-associated sodium channel mutants, and clarify the mechanism for increased persistent sodium current induced by the R1648H allele. (PMID:16380441)
• analysis of SCN1A parental mosaicism in severe myoclonic epilepsy of infancy (PMID:16430863)
• Novel truncating mutation (2528delG) of the SCN1A gene in a boy with myoclonic epilepsy. (PMID:16505326)
• Two unrelated families in which two children of unaffected parents had deleterious SCN1A mutations, and show evidence of somatic and germline mosaicism in the transmitting parents. (PMID:16541393)
• SCN1A mutations were identified in 11 of 14 patients with alleged vaccine encephalopathy; a diagnosis of a specific epilepsy syndrome was made in all 14 cases. (PMID:16713920)
• Patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A (PMID:17030758)
• A substanial epileptic family background is not present in our SMEI patients with SCN1A mutations. (PMID:17054684)
• This wide spectrum of functional defects observed among SCN1A mutations suggests that SMEI may result from more than a single molecular or cellular mechanism, or require other factors for pathogenesis. (PMID:17054685)
• Understanding of mutant SCN1A dysfunction in an inherited epilepsy syndrome will enable more precise computational studies of abnormal neuronal activity in epilepsy. (PMID:17065438)
• identified the novel p.L1649Q mutation (c.4946T>A) in SCN1A in a North American kindred with familial hemiplegic migraine without associated ataxia or epilepsy; findings establish role of neuronal Na(v)1.1 sodium channels in FHM (PMID:17397047)
• SCN1A polymorphism has a dramatic effect on the proportions of neonate and adult alternative transcripts of SCN1A in adult brain tissue and, the effect of the polymorphism also appears to be modified by Nova2 expression levels. (PMID:17436242)
• SCN1A mutations may confer susceptibility to psychiatric disorders in addition to variable epileptic seizures. (PMID:17507202)
• Nav1.1 plays a critical role in the spike output from parvalbumin-positive interneurons and contributes to epileptic seizures in mice. (PMID:17537961)
• characterization of the 5’ untranslated region of SCN1A gene. (PMID:17544618)
• findings illustrate that SCN1A mutations can cause simple febrile seizures associated with temporal lobe epilepsy, which differ from the characteristic clinical spectrum of generalized epilepsy with febrile seizures plus (PMID:17565594)
• In the Dravet syndrome, Six of the 7 patients (86%) who were tested for SCN1A mutations had positive results. (PMID:17621480)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scn1a	ENSMUSG00000064329
rattus_norvegicus	Scn1a	ENSRNOG00000053122

Paralogs (26): CACNA1G (ENSG00000006283), SCN4A (ENSG00000007314), CACNA1S (ENSG00000081248), CACNA1I (ENSG00000100346), CACNA1F (ENSG00000102001), NALCN (ENSG00000102452), SCN2A (ENSG00000136531), SCN7A (ENSG00000136546), CACNA1A (ENSG00000141837), 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 1 subunit alpha — P35498 (reviewed: P35498)

Alternative names: Sodium channel protein brain I subunit alpha, Sodium channel protein type I subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.1

All UniProt accessions (12): P35498, A0A1B0GUN7, A0A1B0GUX7, A0A1B0GVX7, A0A1B0GWE6, A0A1W2PPJ3, A0A286YEQ8, A0A286YF26, A0A286YFA8, A0A5F9ZHI6, A0A8I5KYC1, A0AAQ5BGN9

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. By regulating the excitability of neurons, ensures that they respond appropriately to synaptic inputs, maintaining the balance between excitation and inhibition in brain neural circuits. Nav1.1 plays a role in controlling the excitability and action potential propagation from somatosensory neurons, thereby contributing to the sensory perception of mechanically-induced pain.

Subunit / interactions. The Nav1.1 voltage-gated sodium channel consists of an ion-conducting alpha subunit SCN1A which is functional on its own regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and beta-4 (SCN4B) subunits. SCN1B and SCN3B are non-covalently associated with SCN1A. SCN2B and SCN4B are disulfide-linked to SCN1A. SCN1B regulates both the expression at the plasma membrane and the voltage dependence of Nav1.1 inactivation. SCN3B and SCN4B reduce Nav1.1 conductance. Probably interacts with TMEM233; modulates the gating properties of NaV1.1. Interacts with FGF13; regulates the steady-state inactivation of Nav.1.1.

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylation at Ser-1516 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.

Disease relevance. Generalized epilepsy with febrile seizures plus 2 (GEFSP2) [MIM:604403] A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. The disease is caused by variants affecting the gene represented in this entry. Dravet syndrome (DRVT) [MIM:607208] A severe form of epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core DRVT. DRVT is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus. The disease is caused by variants affecting the gene represented in this entry. Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC) [MIM:607208] A disorder characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except for the absence of myoclonic seizures. The disease is caused by variants affecting the gene represented in this entry. Migraine, familial hemiplegic, 3 (FHM3) [MIM:609634] A subtype of migraine associated with transient blindness in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. The disease is caused by variants affecting the gene represented in this entry. Febrile seizures, familial, 3A (FEB3A) [MIM:604403] Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 6B (DEE6B) [MIM:619317] A form of epileptic encephalopathy, a heterogeneous group of severe 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. DEE6B is an autosomal dominant condition characterized by onset of seizures in early infancy, profoundly impaired intellectual development, and a hyperkinetic movement disorder. The disease is caused by variants affecting the gene represented in this entry. SCN1A mutations may be involved in Panayiotopoulos syndrome, a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an electroencephalogram that shows shifting and/or multiple foci, often with occipital predominance. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Cardiorespiratory arrest is exceptional.

Activity regulation. Activated by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and AC P0DOC5) eliciting acute pain and mechanical allodynia. Inhibited by the conotoxin GVIIJ. Inhibited by the spider beta/delta-theraphotoxin-Pre1a.

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. The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV.

Similarity. Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.1/SCN1A subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P35498-1	1	yes
P35498-2	2
P35498-3	3

RefSeq proteins (15): NP_001159435, NP_001159436, NP_001189364, NP_001340877, NP_001340878, NP_001340879, NP_001340880, NP_001340881, NP_001340883, NP_001340884, NP_001340886, NP_001340887, NP_001340889, NP_001340890, NP_008851 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001696	Na_channel_asu	Family
IPR005821	Ion_trans_dom	Domain
IPR008051	Na_channel_a1su	Family
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 (631 total): sequence variant 443, helix 53, topological domain 29, transmembrane region 24, turn 13, strand 12, glycosylation site 9, disulfide bond 8, modified residue 8, region of interest 7, compositionally biased region 7, sequence conflict 5, intramembrane region 4, repeat 4, splice variant 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7DTD	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35498-F1	68.97	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 (1): 1574 (key residue that permits the spider beta/delta-theraphotoxin-pre1a to inhibit fast inactivation of the channel)

Post-translational modifications (8): 470, 523, 525, 550, 551, 607, 730, 1516

Disulfide bonds (8): 959–968, 1376–1396, 1741–1756, 277–345, 336–351, 919, 919, 921–927

Glycosylation sites (9): 211, 284, 295, 301, 306, 338, 1378, 1392, 1403

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-445095	Interaction between L1 and Ankyrins
R-HSA-5576892	Phase 0 - rapid depolarisation
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

MSigDB gene sets: 596 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_ADULT_BEHAVIOR, GOBP_MEMBRANE_DEPOLARIZATION_DURING_ACTION_POTENTIAL, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_MUSCLE_CONTRACTION, chr2q24, HNF4_DR1_Q3

GO Biological Process (19): sodium ion transport (GO:0006814), adult walking behavior (GO:0007628), determination of adult lifespan (GO:0008340), neuronal action potential propagation (GO:0019227), neuronal action potential (GO:0019228), nerve development (GO:0021675), sodium ion transmembrane transport (GO:0035725), neuromuscular process controlling posture (GO:0050884), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), establishment of localization in cell (GO:0051649), cardiac muscle cell action potential involved in contraction (GO:0086002), membrane depolarization during action potential (GO:0086010), action potential (GO:0001508), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (5): voltage-gated sodium channel activity (GO:0005248), voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099508), monoatomic ion channel activity (GO:0005216), monoatomic cation channel activity (GO:0005261), sodium channel activity (GO:0005272)

GO Cellular Component (14): voltage-gated sodium channel complex (GO:0001518), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), intercalated disc (GO:0014704), nuclear body (GO:0016604), Z disc (GO:0030018), T-tubule (GO:0030315), node of Ranvier (GO:0033268), neuronal cell body (GO:0043025), axon initial segment (GO:0043194), membrane (GO:0016020), axon (GO:0030424), monoatomic ion channel complex (GO:0034702), sodium channel complex (GO:0034706)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
L1CAM interactions	1
Cardiac conduction	1
Axon guidance	1
Nervous system development	1
Muscle contraction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
transmission of nerve impulse	2
action potential	2
regulation of membrane potential	2
transport	2
monoatomic ion transmembrane transport	2
main axon	2
metal ion transport	1
adult locomotory behavior	1
walking behavior	1
multicellular organismal process	1
nervous system process	1
action potential propagation	1
nervous system development	1
anatomical structure development	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
musculoskeletal movement	1
neuromuscular process	1
sensory perception of pain	1
detection of mechanical stimulus involved in sensory perception	1
establishment of localization	1
cellular localization	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
membrane depolarization	1
monoatomic ion transport	1
transmembrane transport	1
regulation of biological quality	1
cellular process	1
monoatomic cation transport	1
sodium channel activity	1
voltage-gated monoatomic ion channel activity	1
presynaptic membrane	1
regulation of presynaptic membrane potential	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

Protein interactions and networks

STRING

2254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCN1A	SCN1B	Q07699	980
SCN1A	NAV1	Q8NEY1	960
SCN1A	GABRG2	P18507	945
SCN1A	PCDH19	Q8TAB3	936
SCN1A	ATP1A2	P50993	913
SCN1A	SCN2B	O60939	900
SCN1A	SCN4B	Q8IWT1	892
SCN1A	KCNQ2	O43526	882
SCN1A	SCN2A	Q99250	875
SCN1A	PCDH10	Q9P2E7	858
SCN1A	CDKL5	O76039	853
SCN1A	STXBP1	P61764	844
SCN1A	GABRA1	P14867	782
SCN1A	KCNK18	Q7Z418	764
SCN1A	PVALB	P20472	763

IntAct

6 interactions, top by confidence:

A	B	Type	Score
NEDD4	SCN1A	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	SCN1A	psi-mi:“MI:0407”(direct interaction)	0.440
SMURF2	SCN1A	psi-mi:“MI:0407”(direct interaction)	0.440
ESR2		psi-mi:“MI:0914”(association)	0.350
NEDD8	PRPF3	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): SCN1A (Affinity Capture-MS), SCN1A (Affinity Capture-MS), SCN1B (Affinity Capture-Western), SCN4B (Affinity Capture-Western), CALM1 (Reconstituted Complex), Calm1 (Reconstituted Complex), Calm1 (Two-hybrid), SCN1A (Affinity Capture-Western), SCN1A (Protein-peptide), SCN1A (Affinity Capture-MS), SCN1A (Protein-peptide), SCN1A (Protein-peptide), SCN1A (Cross-Linking-MS (XL-MS)), SCN1A (Co-fractionation), DHCR24 (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

12 interactions.

A	Effect	B	Mechanism
SCN1A	“up-regulates quantity”	sodium(1+)	relocalization
FGF13	“down-regulates activity”	SCN1A	binding
FGF12	“down-regulates activity”	SCN1A	binding
FGF14	“down-regulates activity”	SCN1A	binding
FGF11	“down-regulates activity”	SCN1A	binding
SCN1A	up-regulates	Action_potential
NEDD4L	“down-regulates quantity by destabilization”	SCN1A	ubiquitination
ESR1	“down-regulates quantity by repression”	SCN1A	“transcriptional regulation”
ESR2	“down-regulates quantity by repression”	SCN1A	“transcriptional regulation”
TNF	“up-regulates quantity by expression”	SCN1A	“transcriptional regulation”
TNF	“up-regulates activity”	SCN1A
IL10	“down-regulates quantity by repression”	SCN1A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

2848 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	889
Likely pathogenic	315
Uncertain significance	777
Likely benign	409
Benign	86

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012967	NM_001165963.4(SCN1A):c.919G>T (p.Glu307Ter)	Pathogenic
1023377	NM_001165963.4(SCN1A):c.965-5A>G	Pathogenic
1027785	NM_001165963.4(SCN1A):c.1662+1G>C	Pathogenic
1054402	NC_000002.11:g.(?165946660)(167168266_?)del	Pathogenic
1056951	NM_001165963.4(SCN1A):c.1199T>C (p.Met400Thr)	Pathogenic
1057584	NM_001165963.4(SCN1A):c.866A>T (p.Glu289Val)	Pathogenic
1061224	NM_001165963.4(SCN1A):c.1149C>A (p.Phe383Leu)	Pathogenic
1064524	NM_001165963.4(SCN1A):c.1807_1808del (p.Ser603fs)	Pathogenic
1065622	NM_001165963.4(SCN1A):c.5120T>C (p.Phe1707Ser)	Pathogenic
1066562	NM_001165963.4(SCN1A):c.2848G>A (p.Gly950Arg)	Pathogenic
1066871	NM_001165963.4(SCN1A):c.172G>A (p.Gly58Arg)	Pathogenic
1067278	NM_001165963.4(SCN1A):c.984_986del (p.Glu328_Gly329delinsAsp)	Pathogenic
1068636	NM_001165963.4(SCN1A):c.243C>A (p.Asp81Glu)	Pathogenic
1068660	NM_001165963.4(SCN1A):c.2496G>A (p.Trp832Ter)	Pathogenic
1068872	NC_000002.11:g.(?_166900200)_166907805del	Pathogenic
1069247	NM_001165963.4(SCN1A):c.2513_2514del (p.Phe838fs)	Pathogenic
1069251	NM_001165963.4(SCN1A):c.2244G>A (p.Trp748Ter)	Pathogenic
1069294	NM_001165963.4(SCN1A):c.1659_1660insT (p.Gln554fs)	Pathogenic
1069295	NM_001165963.4(SCN1A):c.509_510del (p.Leu170fs)	Pathogenic
1070475	NM_001165963.4(SCN1A):c.1324del (p.Ala442fs)	Pathogenic
1070649	NM_001165963.4(SCN1A):c.2855G>A (p.Trp952Ter)	Pathogenic
1071662	NM_001165963.4(SCN1A):c.231_247del (p.Glu78fs)	Pathogenic
1071810	NM_001165963.4(SCN1A):c.2862G>C (p.Glu954Asp)	Pathogenic
1072203	NM_001165963.4(SCN1A):c.1439C>A (p.Ser480Ter)	Pathogenic
1072366	NM_001165963.4(SCN1A):c.1517del (p.Gln506fs)	Pathogenic
1073133	NM_001165963.4(SCN1A):c.1008T>A (p.Cys336Ter)	Pathogenic
1073267	NM_001165963.4(SCN1A):c.2887del (p.Ala963fs)	Pathogenic
1073570	NM_001165963.4(SCN1A):c.2341_2344del (p.Asn781fs)	Pathogenic
1073663	NM_001165963.4(SCN1A):c.541del (p.Glu181fs)	Pathogenic
1073684	NM_001165963.4(SCN1A):c.1972del (p.Ser658fs)	Pathogenic

SpliceAI

3882 predictions. Top by Δscore:

Variant	Effect	Δscore
2:165992418:CATAC:C	acceptor_gain	1.0000
2:165992420:TAC:T	acceptor_gain	1.0000
2:165994140:TCTTA:T	donor_loss	1.0000
2:165994141:CTTA:C	donor_loss	1.0000
2:165994142:TTA:T	donor_loss	1.0000
2:165994143:TA:T	donor_loss	1.0000
2:165994289:G:C	donor_gain	1.0000
2:165994412:TTGTT:T	acceptor_gain	1.0000
2:165994413:TGTT:T	acceptor_gain	1.0000
2:165994417:C:CC	acceptor_gain	1.0000
2:165996007:T:TA	donor_gain	1.0000
2:165996011:A:AC	donor_gain	1.0000
2:165996011:ACT:A	donor_gain	1.0000
2:165996012:C:CC	donor_gain	1.0000
2:165996012:CT:C	donor_gain	1.0000
2:165996012:CTC:C	donor_gain	1.0000
2:165996120:A:C	acceptor_gain	1.0000
2:165998036:A:AC	donor_gain	1.0000
2:165998036:ATCTT:A	donor_gain	1.0000
2:165998176:C:CA	acceptor_loss	1.0000
2:165998177:T:A	acceptor_loss	1.0000
2:165999717:ACTT:A	donor_loss	1.0000
2:165999719:TTACA:T	donor_loss	1.0000
2:165999720:TACAT:T	donor_loss	1.0000
2:165999721:A:AC	donor_gain	1.0000
2:165999721:ACAT:A	donor_loss	1.0000
2:165999722:C:CA	donor_gain	1.0000
2:166002470:A:AC	donor_gain	1.0000
2:166002471:C:CC	donor_gain	1.0000
2:166002471:CAA:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012552 (2:165996533 C>T), RS1000021111 (2:166073015 A>G), RS1000026703 (2:166033435 G>C,T), RS1000036679 (2:166033201 T>C), RS1000049403 (2:166098145 C>G), RS1000173124 (2:166130581 G>T), RS1000187200 (2:166138081 A>T), RS1000219225 (2:166073994 A>G), RS1000251004 (2:166037559 T>G), RS1000261196 (2:166026970 G>A), RS1000281229 (2:166150884 C>G,T), RS1000308791 (2:166131832 T>A), RS1000331327 (2:166013438 T>A), RS1000377467 (2:166003763 A>G), RS1000381899 (2:166021158 T>C)

Disease associations

OMIM: gene MIM:182389 | disease phenotypes: MIM:604403, MIM:609634, MIM:619317, MIM:607208, MIM:607745, MIM:613721, MIM:613863, MIM:208500, MIM:256100, MIM:201300, MIM:308350, MIM:141500, MIM:604233, MIM:209850, MIM:618468, MIM:117100, MIM:121210

GenCC curated gene-disease

Disease	Classification	Inheritance
generalized epilepsy with febrile seizures plus, type 2	Definitive	Autosomal dominant
developmental and epileptic encephalopathy, 6A	Definitive	Autosomal dominant
Dravet syndrome	Definitive	Autosomal dominant
migraine, familial hemiplegic, 3	Strong	Autosomal dominant
generalized epilepsy with febrile seizures plus	Strong	Autosomal dominant
genetic developmental and epileptic encephalopathy	Strong	Autosomal dominant
familial hemiplegic migraine	Moderate	Autosomal dominant
arthrogryposis	Moderate	Autosomal dominant
myoclonic-astatic epilepsy	Supportive	Unknown
Lennox-Gastaut syndrome	Supportive	Autosomal dominant
malignant migrating partial seizures of infancy	Supportive	Autosomal dominant
familial or sporadic hemiplegic migraine	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AD
generalized epilepsy with febrile seizures plus	Definitive	AD
Dravet syndrome	Definitive	AD
familial hemiplegic migraine	Moderate	AD

Mondo (39): developmental and epileptic encephalopathy (MONDO:0100620), early-infantile DEE (MONDO:0800491), generalized epilepsy with febrile seizures plus, type 2 (MONDO:0011461), migraine, familial hemiplegic, 3 (MONDO:0012320), developmental and epileptic encephalopathy 6B (MONDO:0030268), Dravet syndrome (MONDO:0100135), developmental and epileptic encephalopathy, 6A (MONDO:0100079), seizures, benign familial infantile, 3 (MONDO:0011904), developmental and epileptic encephalopathy, 11 (MONDO:0013388), generalized epilepsy with febrile seizures plus, type 7 (MONDO:0013470), Jeune syndrome (MONDO:0018770), nephronophthisis (MONDO:0019005), neuropathy, hereditary sensory and autonomic, type 2A (MONDO:0024309), epilepsy (MONDO:0005027), developmental and epileptic encephalopathy, 1 (MONDO:0010632)

Orphanet (15): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Dravet syndrome (Orphanet:33069), Genetic epilepsy with febrile seizure plus (Orphanet:36387), Familial or sporadic hemiplegic migraine (Orphanet:569), Self-limited neonatal-infantile epilepsy (Orphanet:140927), Self-limited infantile epilepsy (Orphanet:306), Jeune syndrome (Orphanet:474), Nephronophthisis (Orphanet:655), Hereditary sensory and autonomic neuropathy type 2 (Orphanet:970), Non-specific syndromic intellectual disability (Orphanet:528084), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Early myoclonic encephalopathy (Orphanet:1935), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

228 total (30 of 228 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000289	Broad philtrum
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000466	Limited neck range of motion
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000568	Microphthalmia
HP:0000575	Scotoma
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000709	Psychosis

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001662_3	Generalized epilepsy	4.000000e-06
GCST002170_1	Mesial temporal lobe epilepsy with hippocampal sclerosis	4.000000e-08
GCST002170_2	Mesial temporal lobe epilepsy with hippocampal sclerosis	3.000000e-09
GCST002547_1	Epilepsy	9.000000e-10
GCST002547_9	Epilepsy	1.000000e-07
GCST002672_2	Febrile seizures	2.000000e-16
GCST002673_2	Febrile seizures (MMR vaccine-unrelated)	2.000000e-09
GCST002674_4	Febrile seizures (MMR vaccine-related)	3.000000e-12
GCST007343_2	Epilepsy	2.000000e-13
GCST007352_1	Focal epilepsy	7.000000e-09
GCST007353_3	Generalized epilepsy	5.000000e-08
GCST009200_1	Whole brain grey matter density	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006519	MMR-related febrile seizures
EFO:0010306	Grey matter density measurement

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D001176	Arthrogryposis	C05.550.150; C05.651.102; C05.660.077; C16.131.621.077
D001321	Autistic Disorder	F03.625.164.113.500
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
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C565162	Febrile Convulsions, Familial, 1 (supp.)
C567827	Generalized Epilepsy With Febrile Seizures Plus, 7 (supp.)
C565809	Generalized Epilepsy With Febrile Seizures Plus, Type 1 (supp.)
C565810	Generalized Epilepsy With Febrile Seizures Plus, Type 2 (supp.)
C565808	Generalized Epilepsy with Febrile Seizures Plus (supp.)
C537571	Jeune syndrome (supp.)
C566500	Migraine, Familial Hemiplegic, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1845 (SINGLE PROTEIN), CHEMBL2096682 (PROTEIN FAMILY), CHEMBL2331043 (PROTEIN FAMILY), CHEMBL4523668 (PROTEIN COMPLEX), CHEMBL4630760 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

94 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 492,348 (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
CHEMBL1200606	MEXILETINE HYDROCHLORIDE	4	4,087
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
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

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2298771	Efficacy	4	carbamazepine;oxcarbazepine	Epilepsy
rs2298771	Efficacy	4	carbamazepine;clobazam;ethosuximide;lamotrigine;levetiracetam;oxcarbazepine;valproic acid	Epilepsy
rs3812718	Dosage	2B	carbamazepine	Epilepsy
rs3812718	Efficacy	3	carbamazepine	Epilepsy
rs3812718	Dosage	3	phenytoin	Epilepsy

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2298771	SCN1A	4	-2.50	2	carbamazepine;oxcarbazepine;carbamazepine;clobazam;ethosuximide;lamotrigine;levetiracetam;oxcarbazepine;valproic acid
rs3812718	SCN1A	2B	15.25	3	carbamazepine;phenytoin
rs10188577	SCN1A		0.00	0
rs10167228	SCN1A		0.00	0
rs121918623	SCN1A		0.00	0
rs121917953	SCN1A		0.00	0

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 (10 total), top 10:

Ligand	Action	Affinity	Parameter
μ-conotoxin SmIIIA	Pore blocker	8.4	pKi
ATX-II	Slows inactivation	8.2	pEC50
ICA-121431	Channel blocker	7.72	pIC50
GNE-131	Inhibition	7.35	pIC50
relutrigine	Inhibition	6.96	pIC50
cangitoxin II	Slows inactivation	6.8	pEC50
Bc-III	Slows inactivation	6.5	pEC50
AFT-II	Slows inactivation	6.4	pEC50
GNE-616	Inhibition	6.0	pKd
cannabidiol	Channel blocker	4.9	pIC50

Binding affinities (BindingDB)

839 measured of 914 human assays (914 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

670 potent at pChembl≥5 of 1140 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.64	IC50	2.3	nM	SAXITOXIN
8.39	IC50	4.1	nM	TETRODOTOXIN
8.22	IC50	6	nM	CHEMBL3662190
8.10	EC50	7.9	nM	CHEMBL5082582
7.97	IC50	10.6	nM	CHEMBL3657855
7.96	IC50	11	nM	CHEMBL3657855
7.92	IC50	12	nM	CHEMBL4293085
7.82	IC50	15.02	nM	BREVETOXIN B
7.80	IC50	16	nM	CHEMBL3318132
7.70	IC50	20	nM	CHEMBL4276884
7.60	IC50	25	nM	CHEMBL6143914
7.51	IC50	31	nM	CHEMBL5884546
7.50	IC50	32	nM	CHEMBL3617053
7.43	IC50	37	nM	CHEMBL4588728
7.35	IC50	45	nM	CHEMBL4290579
7.32	IC50	48	nM	CHEMBL3662077
7.30	IC50	50	nM	CHEMBL5890093
7.28	IC50	53	nM	CHEMBL4279238
7.27	IC50	54	nM	PIMOZIDE
7.05	IC50	90	nM	CHEMBL4854735
7.04	EC50	92	nM	CHEMBL5077579
7.00	IC50	100	nM	CHEMBL4471012
6.99	EC50	102.1	nM	CHEMBL5093878
6.95	IC50	112	nM	CHEMBL4285790
6.95	IC50	112	nM	CHEMBL5876162
6.94	IC50	114	nM	CHEMBL5756729
6.91	EC50	124.1	nM	CHEMBL5091679
6.90	EC50	125.8	nM	CHEMBL5083412
6.90	EC50	125.8	nM	CHEMBL5091623
6.88	IC50	133	nM	CHEMBL5924319
6.85	Kd	140	nM	CHEMBL4471012
6.85	Kd	140	nM	CHEMBL4444707
6.85	IC50	142	nM	CHEMBL5892019
6.83	IC50	147	nM	CHEMBL5811440
6.80	IC50	159	nM	CHEMBL5745944
6.77	EC50	171.5	nM	CHEMBL5084333
6.74	IC50	182	nM	CHEMBL6050574
6.72	IC50	192	nM	CHEMBL4444707
6.70	IC50	202	nM	CHEMBL5094715
6.67	IC50	216	nM	CHEMBL2324411
6.61	IC50	245	nM	CHEMBL6022263
6.58	IC50	260	nM	CHEMBL5765898
6.57	IC50	270	nM	LOPERAMIDE
6.56	IC50	277	nM	CHEMBL5842264
6.55	IC50	283	nM	CHEMBL5953924
6.55	IC50	280	nM	FLUPERAMIDE
6.52	IC50	301	nM	CHEMBL5749965
6.52	IC50	303	nM	CHEMBL5985658
6.52	IC50	300	nM	PRENYLAMINE
6.51	IC50	309	nM	CHEMBL4217988

PubChem BioAssay actives

174 with measured affinity, of 859 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
[(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,8,9-tetrahydro-1H-pyrrolo[1,2-c]purin-4-yl]methyl carbamate	1525388: Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay	ic50	0.0023	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	1525388: Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay	ic50	0.0041	uM
5-cyclopropyl-N-cyclopropylsulfonyl-2-fluoro-4-[(6-methylspiro[2.5]octan-6-yl)methoxy]benzamide	1525388: Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay	ic50	0.0060	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S,77S)-59-[(2-aminoacetyl)amino]-13,48,65-tris(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30,77-dibenzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,74-bis(hydroxymethyl)-27-(1H-imidazol-5-ylmethyl)-36-(1H-indol-3-ylmethyl)-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.0079	uM
4-(1-adamantylmethoxy)-N-(azetidin-1-ylsulfonyl)-5-cyclopropyl-2-fluorobenzamide	1831647: Inhibition of full length human Nav1.1 expressed in HEK cells by whole cell voltage clamp analysis	ic50	0.0106	uM
N-[[3-chloro-4-(trifluoromethoxy)phenyl]methyl]-3-fluoro-4-(1,2,4-thiadiazol-5-ylsulfamoyl)benzamide	1411467: Inhibition of human NaV1.1	ic50	0.0120	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
(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	1525388: Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay	ic50	0.0160	uM
N-[[3-chloro-4-(trifluoromethoxy)phenyl]methyl]-3-fluoro-4-(1,3-thiazol-2-ylsulfamoyl)benzamide	1411467: Inhibition of human NaV1.1	ic50	0.0200	uM
2,2-diphenyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]acetamide	1246059: Inhibition of human NaV1.1 channel by patch clamp electrophysiology assay	ic50	0.0200	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	1525388: Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay	ic50	0.0370	uM
N-[7-(1-adamantylmethoxy)-6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl]cyclopropanesulfonamide	1410603: Inhibition of inactivated state of recombinant human NaV1.1 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -40 mV holding potential by PX automated voltage clamp method	ic50	0.0450	uM
5-cyclopropyl-N-cyclopropylsulfonyl-4-[(4,4-difluoro-1-methylcyclohexyl)methoxy]-2-fluorobenzamide	1960145: Inhibition of human Nav1.1 alpha subunit expressed in HEK293 cells co-expressing beta1 subunit at -40 mV holding potential by PatchXpress automated voltage clamp electrophysiology technique	ic50	0.0480	uM
N-[7-(1-adamantylmethoxy)-6-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanesulfonamide	1410603: Inhibition of inactivated state of recombinant human NaV1.1 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -40 mV holding potential by PX automated voltage clamp method	ic50	0.0530	uM
Pimozide	1207165: Inhibition of Na channel (species unknown)	ic50	0.0540	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	1754510: Inhibition of human Nav1.1 by V1/2 protocol based analysis	ic50	0.0900	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S,77S)-59-[(2-aminoacetyl)amino]-13,27,48-tris(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30,77-dibenzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,65,74-tris(hydroxymethyl)-36-(1H-indol-3-ylmethyl)-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.0920	uM
N-cyclopropylsulfonyl-1-[(3R)-1-[(1R)-1-(3,5-dichlorophenyl)ethyl]pyrrolidin-3-yl]-6-fluoro-3-methylindazole-5-carboxamide	1922056: Inhibition of human Nav1.1 at -45 mV holding potential by manual patch-clamp assay	ic50	0.1000	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S,77S)-59-[(2-aminoacetyl)amino]-13,48-bis(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30,77-dibenzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,74-bis(hydroxymethyl)-27-(1H-imidazol-5-ylmethyl)-36-(1H-indol-3-ylmethyl)-65-methyl-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.1021	uM
N-[6-cyclopropyl-7-[(3,5-dichlorophenoxy)methyl]-[1,2,4]triazolo[4,3-a]pyridin-3-yl]methanesulfonamide	1410603: Inhibition of inactivated state of recombinant human NaV1.1 expressed in HEK293 cell membranes coexpressing Nav beta1 subunit assessed as decrease in sodium current amplitude at -40 mV holding potential by PX automated voltage clamp method	ic50	0.1120	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S,77S)-59-[(2-aminoacetyl)amino]-13,27,48-tris(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30,77-dibenzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,74-bis(hydroxymethyl)-36-(1H-indol-3-ylmethyl)-65-methyl-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.1241	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S,77S)-59-[(2-aminoacetyl)amino]-13,27,48-tris(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30-benzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,74-bis(hydroxymethyl)-36-(1H-indol-3-ylmethyl)-65-methyl-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-77-propan-2-yl-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.1258	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2S,4S)-1-[(2S)-4-amino-2-[[(1R,4S,7S,10S,13S,19R,24R,27S,30S,33S,36S,42R,45S,48S,51S,54R,59R,62S,65S,68S,74S)-59-[(2-aminoacetyl)amino]-13,27,48,65-tetrakis(4-aminobutyl)-33,45-bis(2-amino-2-oxoethyl)-30-benzyl-62-[(2S)-butan-2-yl]-4,51,68-tris[(1R)-1-hydroxyethyl]-10,74-bis(hydroxymethyl)-36-(1H-indol-3-ylmethyl)-7-(2-methylpropyl)-2,5,8,11,14,17,26,29,32,35,38,41,44,47,50,53,60,63,66,69,72,75,78,85-tetracosaoxo-21,22,56,57,81,82-hexathia-3,6,9,12,15,18,25,28,31,34,37,40,43,46,49,52,61,64,67,70,73,76,79,84-tetracosazatricyclo[40.37.4.219,54]pentaoctacontane-24-carbonyl]amino]-4-oxobutanoyl]-4-hydroxypyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.1258	uM
4-[[1-[[2-chloro-5-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]methoxy]-5-cyclopropyl-2-fluoro-N-methylsulfonylbenzamide	1525418: Binding affinity to human recombinant Nav1.1 by radioligand binding assay	kd	0.1400	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S,4S)-1-[(2R)-6-amino-2-[[(2S)-4-amino-2-[[(1R,4S,7S,10S,13R,18R,21S,27S,30S,36S,39S,42R,45S,48S,51S,54S,60R,65R,68S,71S,74S,77S)-18-[(2-aminoacetyl)amino]-7-(4-aminobutyl)-4,54,74-tris(2-amino-2-oxoethyl)-71-benzyl-21-[(2S)-butan-2-yl]-10,45-bis[(1R)-1-hydroxyethyl]-36,51-bis(hydroxymethyl)-68-(1H-imidazol-5-ylmethyl)-77-(1H-indol-3-ylmethyl)-48-(2-methylpropyl)-39-(2-methylsulfanylethyl)-3,6,9,12,19,22,28,31,34,37,40,43,46,49,52,55,58,67,70,73,76,79,82,87-tetracosaoxo-30-propan-2-yl-15,16,62,63,84,85-hexathia-2,5,8,11,20,23,29,32,35,38,41,44,47,50,53,56,59,66,69,72,75,78,81,88-tetracosazatetracyclo[40.40.4.213,60.023,27]octaoctacontane-65-carbonyl]amino]-4-oxobutanoyl]amino]hexanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1815030: Modulator activity at human Nav1.1 expressed in Xenopus laevis oocytes assessed as elicitation in sodium current measured after 1 to 4 days by two-electrode voltage clamp assay	ec50	0.1715	uM
5-cyclopropyl-4-[[1-[(1S)-1-(3,5-dichlorophenyl)ethyl]piperidin-4-yl]methoxy]-2-fluoro-N-methylsulfonylbenzamide	1831647: Inhibition of full length human Nav1.1 expressed in HEK cells by whole cell voltage clamp analysis	ic50	0.2020	uM
4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1457690: Inhibition of human NaV1.1 expressed in HEK cells assessed as half inactivation potential at -120 mV holding potential by automated patch clamp method	ic50	0.2160	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-[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
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	1365874: Inhibition of human Nav1.1 expressed in HEK cells by patch clamp electrophysiology method	ic50	0.3090	uM
6-[4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine	1302077: Inhibition of 10 Hz stimulated Nav1.1 (unknown origin) by manual patch clamp method	ic50	0.4000	uM
1-benzhydryl-4-[(E)-3-phenylprop-2-enyl]piperazine	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	0.4400	uM
4-[[3-chloro-4-(trifluoromethoxy)phenyl]methoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1411467: Inhibition of human NaV1.1	ic50	0.4550	uM
3-[4-[3-(3,4,5-trimethoxybenzoyl)oxypropyl]-1,4-diazepan-1-yl]propyl 3,4,5-trimethoxybenzoate	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	0.6000	uM
8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	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	0.6000	uM
1-[bis(4-fluorophenyl)methyl]-4-[(E)-3-phenylprop-2-enyl]piperazine	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	0.6000	uM
2-[1-[3-(4-benzoylphenoxy)-2-hydroxypropyl]piperidin-4-yl]-3H-isoindol-1-one	1254882: Inhibition of human NaV1.1 by IonWorks quattro automated electrophysiology assay	ic50	0.6700	uM
4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide	1457690: Inhibition of human NaV1.1 expressed in HEK cells assessed as half inactivation potential at -120 mV holding potential by automated patch clamp method	ic50	0.6770	uM
Droperidol	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	0.7400	uM
(R)-[(2S,4R,5S)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-[6-(3-methylbutoxy)quinolin-4-yl]methanol	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	0.7400	uM
N-[1-[2-hydroxy-3-[4-(trifluoromethyl)phenoxy]propyl]piperidin-4-yl]benzamide	1254882: Inhibition of human NaV1.1 by IonWorks quattro automated electrophysiology assay	ic50	0.8000	uM
1-(2-phenylcyclopentyl)-azacyclotridecan-2-imine	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	0.8000	uM
N-benzyl-N-[3-(2-methylpropoxy)-2-pyrrolidin-1-ylpropyl]aniline	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	0.8400	uM
2-[1-[2-hydroxy-3-[2-methoxy-4-(trifluoromethyl)phenoxy]propyl]piperidin-4-yl]-3H-isoindol-1-one	1254882: Inhibition of human NaV1.1 by IonWorks quattro automated electrophysiology assay	ic50	0.9100	uM
2-[1-[3-(3-benzoylphenoxy)-2-hydroxypropyl]piperidin-4-yl]-3H-isoindol-1-one	1254882: Inhibition of human NaV1.1 by IonWorks quattro automated electrophysiology assay	ic50	0.9200	uM
[(1S,2S)-2-[2-[3-(1H-benzimidazol-2-yl)propyl-methylamino]ethyl]-6-fluoro-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl] 2-methoxyacetate	1207161: Inhibition of Na channel (species unknown)	ic50	0.9800	uM
Cyproheptadine	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	1.0000	uM
2-[1-[2-hydroxy-3-[3-(trifluoromethyl)phenoxy]propyl]piperidin-4-yl]-3H-isoindol-1-one	1254882: Inhibition of human NaV1.1 by IonWorks quattro automated electrophysiology assay	ic50	1.2000	uM
N-cyclopropylsulfonyl-6-fluoro-3-methyl-1-[5-(trifluoromethyl)-3-pyridinyl]indole-5-carboxamide	1948700: Inhibition of human Nav1.1/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis	ic50	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	7
trichostatin A	decreases reaction, affects cotreatment, increases expression, affects expression	4
Benzo(a)pyrene	decreases expression	3
Tetrachlorodibenzodioxin	increases expression, decreases expression, decreases reaction	3
Aflatoxin B1	affects expression, decreases expression, increases expression	3
Carbamazepine	decreases response to substance, affects response to substance	2
Endosulfan	increases expression, decreases expression, decreases reaction	2
Estradiol	decreases expression	2
Phenytoin	affects response to substance	2
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
cypermethrin	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Azathioprine	decreases expression	1
Cannabidiol	decreases activity	1
Diethylhexyl Phthalate	increases expression	1
Nickel	affects expression, decreases reaction	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1

ChEMBL screening assays

149 unique, capped per target: 115 binding, 18 functional, 14 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017615	Binding	Inhibition of human Nav1.1 expressed in HEK293 cells assessed as change in membrane potential using MP-red voltage sensitive dye at 10 uM	Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. — J Med Chem
CHEMBL3883158	ADMET	Inhibition of human Nav1.1 expressed in HEK293 cells co-expressing human beta1 and beta2 assessed as reduction in peak frequency currents by whole-cell voltage-clamp method	Fused heterocyclic compounds as ion channel modulators
CHEMBL6115360	Toxicity	Inhibition of Nav1.1 (unknown origin) at 30 uM relative to control	Development and characterization of pyridyl carboxamides as potent and highly selective Nav1.8 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

57 cell lines: 51 induced pluripotent stem cell, 3 transformed cell line, 3 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2H48	HEK1.1	Transformed cell line	Female
CVCL_A1QQ	USTCi001-A-2	Induced pluripotent stem cell	Male
CVCL_A1XH	UNIMGi001-A	Induced pluripotent stem cell	Male
CVCL_A1XI	UNIMGi002-A	Induced pluripotent stem cell	Male
CVCL_A3YP	D1 [Human Dravet fibroblast]	Finite cell line	Male
CVCL_A3YQ	D2 [Human Dravet fibroblast]	Finite cell line	Female
CVCL_A3YR	D3 [Human Dravet fibroblast]	Finite cell line	Male
CVCL_A3ZB	DS-1-iPSC	Induced pluripotent stem cell	Female
CVCL_A3ZC	DS-2-iPSC	Induced pluripotent stem cell	Female
CVCL_A4DS	USTCi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
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
NCT03936777	PHASE3	COMPLETED	A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome
NCT04462770	PHASE3	RECRUITING	A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
NCT04611438	PHASE3	UNKNOWN	Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
NCT04940624	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children and Young Adults With Dravet Syndrome
NCT05163314	PHASE3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT05560282	PHASE3	TERMINATED	Fenfluramine for Adult Dravet Patients
NCT06118255	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT06660394	PHASE3	RECRUITING	A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS)
NCT06872125	PHASE3	RECRUITING	A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen in Patients With Dravet Syndrome
NCT00004776	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Topiramate for Lennox-Gastaut Syndrome
NCT01146951	PHASE3	COMPLETED	A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
NCT01151540	PHASE3	COMPLETED	A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
NCT01160770	PHASE3	COMPLETED	Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
NCT01405053	PHASE3	COMPLETED	Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
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