Dravet syndrome

disease

On this page

Also known as DravetDSmyoclonic epilepsy, severe, of infancysevere myoclonic epilepsy of infancySMESMEB

Summary

Dravet syndrome (MONDO:0100135) is a disease caused by SCN1A (GenCC Definitive), with 12 cohort genes and 89 clinical trials. The dominant Reactome pathway is Interaction between L1 and Ankyrins (5 cohort genes). Top therapeutic interventions include cannabidiol, fenfluramine, and stiripentol.

At a glance

Causal gene: SCN1A (GenCC Definitive)
Cohort genes: 12
ClinVar variants: 1,292
Clinical trials: 89

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Dravet syndrome
Mondo ID	MONDO:0100135
DOID	DOID:0060171, DOID:0080422
ICD-10-CM	G40.83
ICD-11	1255654700
NCIT	C116573
SNOMED CT	230437002
UMLS	C0751122
MedGen	148243
GARD	0010430
NORD	1061
Is cancer (heuristic)	no

Also known as: Dravet · Dravet syndrome · DS · myoclonic epilepsy, severe, of infancy · severe myoclonic epilepsy of infancy · SME · SMEB

Data availability: 1,292 ClinVar variants · 13 ClinGen variant curations · 2 GenCC gene-disease records · 58 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › Dravet syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

247 pathogenic, 121 likely benign, 120 uncertain significance, 38 pathogenic/likely pathogenic, 30 conflicting classifications of pathogenicity, 30 likely pathogenic, 12 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1330194	GRCh37/hg19 2q24.3(chr2:166152284-167760450)x1	GALNT3	Pathogenic	criteria provided, single submitter
1065174	NM_001165963.4(SCN1A):c.3612G>A (p.Trp1204Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
1179013	NM_001165963.4(SCN1A):c.5488C>T (p.Gln1830Ter)	LOC102724058	Pathogenic	no assertion criteria provided
12882	NM_001165963.4(SCN1A):c.4943G>A (p.Arg1648His)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
12895	NM_001165963.4(SCN1A):c.4831G>T (p.Val1611Phe)	LOC102724058	Pathogenic	no assertion criteria provided
12899	NC_000002.12:g.(?165985812)(166002754_166009718)del	LOC102724058	Pathogenic	no assertion criteria provided
12900	NM_001165963.4(SCN1A):c.4002+1195_4284+346delinsTATT	LOC102724058	Pathogenic	no assertion criteria provided
1300153	NM_001165963.4(SCN1A):c.5540_5543dup (p.Gln1848fs)	LOC102724058	Pathogenic	criteria provided, single submitter
1328963	NM_001165963.4(SCN1A):c.4423T>G (p.Leu1475Val)	LOC102724058	Pathogenic	no assertion criteria provided
1393964	NM_001165963.4(SCN1A):c.4313T>C (p.Met1438Thr)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1445952	NM_001165963.4(SCN1A):c.3124C>T (p.Gln1042Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
1454054	NM_001165963.4(SCN1A):c.4322C>T (p.Ala1441Val)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167639	NM_001165963.4(SCN1A):c.3733C>T (p.Arg1245Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
1705826	NM_001165963.4(SCN1A):c.4418T>C (p.Phe1473Ser)	LOC102724058	Pathogenic	criteria provided, single submitter
1709397	NM_001165963.4(SCN1A):c.5177G>A (p.Trp1726Ter)	LOC102724058	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1801481	NM_001165963.4(SCN1A):c.5564C>A (p.Pro1855His)	LOC102724058	Pathogenic	criteria provided, single submitter
189843	NM_001165963.4(SCN1A):c.4351C>A (p.Pro1451Thr)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189846	NM_001165963.4(SCN1A):c.4302G>A (p.Trp1434Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189849	NM_001165963.4(SCN1A):c.4879_4883dup (p.Tyr1628Ter)	LOC102724058	Pathogenic	criteria provided, single submitter
189850	NM_001165963.4(SCN1A):c.5250_5251insGG (p.Ser1751fs)	LOC102724058	Pathogenic	criteria provided, single submitter
189851	NM_001165963.4(SCN1A):c.5250_5252del (p.Ser1750_Ser1751delinsArg)	LOC102724058	Pathogenic	criteria provided, single submitter
189861	NM_001165963.4(SCN1A):c.3637C>T (p.Arg1213Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189870	NM_001165963.4(SCN1A):c.4906C>T (p.Arg1636Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189877	NM_001165963.4(SCN1A):c.3970_3971dup (p.Leu1324_Arg1325insTer)	LOC102724058	Pathogenic	criteria provided, single submitter
189879	NM_001165963.4(SCN1A):c.3763G>C (p.Ala1255Pro)	LOC102724058	Pathogenic	criteria provided, single submitter
189881	NM_001165963.4(SCN1A):c.5536_5539del (p.Lys1846fs)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189893	NM_001165963.4(SCN1A):c.5780G>C (p.Arg1927Thr)	LOC102724058	Pathogenic	criteria provided, single submitter
189896	NM_001165963.4(SCN1A):c.5674C>T (p.Arg1892Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts
189907	NM_001165963.4(SCN1A):c.5082T>G (p.Tyr1694Ter)	LOC102724058	Pathogenic	criteria provided, single submitter
189911	NM_001165963.4(SCN1A):c.4573C>T (p.Arg1525Ter)	LOC102724058	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 33 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SCN1A	Definitive	Autosomal dominant	Dravet syndrome	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
SCN1B	Orphanet:130	Brugada syndrome
SCN1B	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN1B	Orphanet:33069	Dravet syndrome
SCN1B	Orphanet:334	Hereditary atrial fibrillation
SCN1B	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1B	Orphanet:871	Hereditary progressive cardiac conduction defect
SCN2A	Orphanet:140927	Self-limited neonatal-infantile epilepsy
SCN2A	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN2A	Orphanet:2131	Alternating hemiplegia of childhood
SCN2A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN2A	Orphanet:306	Self-limited infantile epilepsy
SCN2A	Orphanet:33069	Dravet syndrome
SCN2A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN2A	Orphanet:697160	Infantile epileptic spasms syndrome
SCN9A	Orphanet:306577	Hereditary sodium channelopathy-related small fibers neuropathy
SCN9A	Orphanet:33069	Dravet syndrome
SCN9A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN9A	Orphanet:46348	Paroxysmal extreme pain disorder
SCN9A	Orphanet:88642	Congenital insensitivity to pain-anosmia-neuropathic arthropathy
SCN9A	Orphanet:90026	Primary erythromelalgia
SCN9A	Orphanet:970	Hereditary sensory and autonomic neuropathy type 2
SELENBP1	Orphanet:562538	Autosomal recessive extra-oral halitosis
MED27	Orphanet:528084	Non-specific syndromic intellectual disability
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
GALNT3	Orphanet:306661	Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	gencc,clinvar
SCN1B	HGNC:10586	ENSG00000105711	Q07699	Sodium channel regulatory subunit beta-1	clinvar
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	clinvar
SCN7A	HGNC:10594	ENSG00000136546	Q01118	Sodium channel protein type 7 subunit alpha	clinvar
SCN9A	HGNC:10597	ENSG00000169432	Q15858	Sodium channel protein type 9 subunit alpha	clinvar
SELENBP1	HGNC:10719	ENSG00000143416	Q13228	Methanethiol oxidase	clinvar
SNX27	HGNC:20073	ENSG00000143376	Q96L92	Sorting nexin-27	clinvar
MED27	HGNC:2377	ENSG00000160563	Q6P2C8	Mediator of RNA polymerase II transcription subunit 27	clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
GALNT3	HGNC:4125	ENSG00000115339	Q14435	Polypeptide N-acetylgalactosaminyltransferase 3	clinvar
SCN1A-AS1	HGNC:54069	ENSG00000236107		SCN1A and SCN9A antisense RNA 1	clinvar
PSMB4	HGNC:9541	ENSG00000159377	P28070	Proteasome subunit beta type-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SCN1B	Sodium channel regulatory subunit beta-1	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
SCN7A	Sodium channel protein type 7 subunit alpha	Sodium leak channel functioning as an osmosensor regulating sodium ion levels in various tissues and organs.
SCN9A	Sodium channel protein type 9 subunit alpha	Pore-forming subunit of Nav1.7, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
SELENBP1	Methanethiol oxidase	Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria.
SNX27	Sorting nexin-27	Involved in the retrograde transport from endosome to plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins.
MED27	Mediator of RNA polymerase II transcription subunit 27	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
TTC21B	Tetratricopeptide repeat protein 21B	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
GALNT3	Polypeptide N-acetylgalactosaminyltransferase 3	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
PSMB4	Proteasome subunit beta type-4	Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins.

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 5 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	4	37.2×	1e-05
Antibody/Immunoglobulin	1	2.4×	0.810
Scaffold/PPI	1	1.4×	0.810
Enzyme (other)	1	1.0×	0.810
Other/Unknown	5	0.8×	0.899

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
SCN1B	Antibody/Immunoglobulin	yes		Ig_V-set, Ig-like_fold, Na_channel_b1/b3
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SCN7A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
SCN9A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SELENBP1	Other/Unknown	no		Se-bd
SNX27	Scaffold/PPI	no		RA_dom, PDZ, PX_dom
MED27	Other/Unknown	no		Mediator_Med27
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
GALNT3	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
SCN1A-AS1	Other/Unknown	no
PSMB4	Other/Unknown	no		Proteasome_sua/b, Proteasome_bsu_CS, Proteasome_beta4

Expression context

Cohort genes with no expression data: 0.

12 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	3
Brodmann (1909) area 23	2
primary visual cortex	2
lateral nuclear group of thalamus	1
cerebellum	1
right hemisphere of cerebellum	1
cerebellar vermis	1
middle temporal gyrus	1
right lung	1
trigeminal ganglion	1
dorsal root ganglion	1
stromal cell of endometrium	1
colonic mucosa	1
mucosa of transverse colon	1
rectum	1
cranial nerve II	1
globus pallidus	1
medial globus pallidus	1
endothelial cell	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
SCN1B	133	ubiquitous	marker	primary visual cortex, right hemisphere of cerebellum, cerebellum
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
SCN7A	226	broad	marker	trigeminal ganglion, sural nerve, right lung
SCN9A	187	ubiquitous	marker	sural nerve, dorsal root ganglion, stromal cell of endometrium
SELENBP1	281	ubiquitous	marker	mucosa of transverse colon, rectum, colonic mucosa
SNX27	292	ubiquitous	marker	medial globus pallidus, globus pallidus, cranial nerve II
MED27	271	ubiquitous	marker	oocyte, endothelial cell, secondary oocyte
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
GALNT3	234	ubiquitous	marker	mucosa of sigmoid colon, bronchial epithelial cell, parotid gland
SCN1A-AS1	129	tissue_specific	marker	sural nerve, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
PSMB4	300	ubiquitous	marker	epithelium of nasopharynx, endometrium epithelium, nasopharynx

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSMB4	3,606
SNX27	3,100
SCN2A	2,810
MED27	2,390
SCN1A	2,287
SELENBP1	1,663
TTC21B	1,588
SCN9A	1,575
SCN1B	1,328
SCN7A	1,240

Intra-cohort edges

A	B	Sources
SCN1A	SCN1B	biogrid_interaction, string_interaction
SCN1A	SCN2A	biogrid_interaction, string_interaction
SCN1B	SCN2A	string_interaction
SCN1B	SCN7A	string_interaction
SCN1B	SCN9A	string_interaction
SCN2A	SCN9A	intact
SCN7A	SCN9A	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSMB4	P28070	146
SCN9A	Q15858	43
SCN1B	Q07699	39
MED27	Q6P2C8	11
SNX27	Q96L92	10
SCN2A	Q99250	5
TTC21B	Q7Z4L5	3
SCN7A	Q01118	2
SCN1A	P35498	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SELENBP1	Q13228	96.85
GALNT3	Q14435	89.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 103. Enrichment computed across 12 evidence-associated genes (9 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	5	204.7×	9e-10	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Phase 0 - rapid depolarisation	5	192.3×	9e-10	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
L1CAM interactions	5	66.8×	2e-07	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Cardiac conduction	5	60.4×	2e-07	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Muscle contraction	5	42.9×	9e-07	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Axon guidance	5	25.1×	1e-05	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Nervous system development	5	23.9×	1e-05	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
Sensory perception of taste	3	112.0×	3e-05	SCN1B, SCN2A, SCN9A
Sensory perception of sweet, bitter, and umami (glutamate) taste	3	92.8×	4e-05	SCN1B, SCN2A, SCN9A
Developmental Biology	6	9.6×	8e-05	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A, MED27
Sensory Perception	3	31.7×	8e-04	SCN1B, SCN2A, SCN9A
FGFR3c ligand binding and activation	1	97.6×	0.080	GALNT3
Defective GALNT3 causes HFTC	1	79.3×	0.080	GALNT3
Antigen processing: Ub, ATP-independent proteasomal degradation	1	63.4×	0.080	PSMB4
Regulation of activated PAK-2p34 by proteasome mediated degradation	1	30.9×	0.080	PSMB4
Regulation of ornithine decarboxylase (ODC)	1	30.2×	0.080	PSMB4
Vpu mediated degradation of CD4	1	29.5×	0.080	PSMB4
Autodegradation of the E3 ubiquitin ligase COP1	1	29.5×	0.080	PSMB4
Ubiquitin-dependent degradation of Cyclin D	1	29.5×	0.080	PSMB4
Cross-presentation of soluble exogenous antigens (endosomes)	1	28.2×	0.080	PSMB4
Vif-mediated degradation of APOBEC3G	1	28.2×	0.080	PSMB4
AUF1 (hnRNP D0) binds and destabilizes mRNA	1	27.6×	0.080	PSMB4
Degradation of AXIN	1	27.6×	0.080	PSMB4
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis	1	27.6×	0.080	PSMB4
GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2	1	27.6×	0.080	PSMB4
Hh mutants are degraded by ERAD	1	27.0×	0.080	PSMB4
SCF-beta-TrCP mediated degradation of Emi1	1	26.4×	0.080	PSMB4
Degradation of DVL	1	26.4×	0.080	PSMB4
Negative regulation of NOTCH4 signaling	1	26.4×	0.080	PSMB4
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	1	26.4×	0.080	PSMB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cardiac muscle cell action potential involved in contraction	5	319.2×	2e-10	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
sodium ion transmembrane transport	5	92.3×	5e-08	SCN1A, SCN1B, SCN2A, SCN7A, SCN9A
neuronal action potential	3	131.3×	4e-05	SCN1A, SCN2A, SCN9A
membrane depolarization during action potential	2	306.4×	4e-04	SCN1A, SCN1B
neuronal action potential propagation	2	255.3×	5e-04	SCN1A, SCN1B
establishment of natural killer cell polarity	1	1532.0×	0.007	SNX27
corticospinal neuron axon guidance	1	1532.0×	0.007	SCN1B
action potential propagation	1	1532.0×	0.007	SCN9A
sodium ion transport	2	49.4×	0.007	SCN1A, SCN2A
intrinsic apoptotic signaling pathway in response to osmotic stress	1	766.0×	0.011	SCN2A
regulation of intraciliary retrograde transport	1	766.0×	0.011	TTC21B
polysaccharide metabolic process	1	510.7×	0.013	GALNT3
membrane depolarization during Purkinje myocyte cell action potential	1	510.7×	0.013	SCN1B
positive regulation of voltage-gated sodium channel activity	1	510.7×	0.013	SCN1B
protein localization to non-motile cilium	1	383.0×	0.016	TTC21B
detection of mechanical stimulus involved in sensory perception	1	255.3×	0.021	SCN9A
negative regulation of eating behavior	1	255.3×	0.021	TTC21B
forebrain dorsal/ventral pattern formation	1	191.5×	0.027	TTC21B
regulation of atrial cardiac muscle cell membrane depolarization	1	170.2×	0.028	SCN1B
cardiac conduction	1	153.2×	0.029	SCN1B
osmosensory signaling pathway	1	139.3×	0.029	SCN7A
locomotion	1	139.3×	0.029	SCN1B
Bergmann glial cell differentiation	1	139.3×	0.029	TTC21B
membrane depolarization during cardiac muscle cell action potential	1	127.7×	0.030	SCN1B
intraciliary retrograde transport	1	102.1×	0.031	TTC21B
detection of mechanical stimulus involved in sensory perception of pain	1	102.1×	0.031	SCN1A
cerebellar Purkinje cell differentiation	1	95.8×	0.031	TTC21B
neuromuscular process controlling posture	1	95.8×	0.031	SCN1A
regulation of sodium ion transmembrane transport	1	95.8×	0.031	SCN1B
chondrocyte development	1	85.1×	0.031	GALNT3

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 6 · Undrugged: 6

Druggability breadth: 7 of 12 evidence-associated genes (58%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN1A	MEXILETINE HYDROCHLORIDE
SCN2A	BEPRIDIL
SCN7A	IMIPRAMINE
SCN9A	IMIPRAMINE
PSMB4	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SCN1A	94	4
SCN9A	36	4
SCN7A	20	4
PSMB4	5	4
SCN1B	2	2
SELENBP1	0	0
SNX27	0	0
MED27	0	0
TTC21B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEXILETINE HYDROCHLORIDE	4	SCN1A, SCN9A
BEPRIDIL	4	SCN1A, SCN2A
DIBUCAINE	4	SCN1A, SCN2A
ARTICAINE	4	SCN1A, SCN2A
BUPIVACAINE	4	SCN1A, SCN2A
IMIPRAMINE	4	SCN1A, SCN2A, SCN7A, SCN9A
DROPERIDOL	4	SCN1A, SCN2A
DICYCLOMINE	4	SCN1A, SCN2A
TETRABENAZINE	4	SCN1A, SCN2A
PHENIRAMINE	4	SCN1A, SCN2A
PRILOCAINE	4	SCN1A, SCN2A
PROPOXYCAINE	4	SCN1A, SCN2A
PROPARACAINE	4	SCN1A, SCN2A
HEXYLCAINE	4	SCN1A, SCN2A
PRAMOXINE	4	SCN1A, SCN2A
BENOXINATE	4	SCN1A, SCN2A
QUINIDINE	4	SCN1A, SCN2A
FELODIPINE	4	SCN1A, SCN2A
PHENYTOIN	4	SCN1A, SCN2A
QUININE	4	SCN1A, SCN2A
NISOLDIPINE	4	SCN1A, SCN2A
NIFEDIPINE	4	SCN1A, SCN2A, SCN7A, SCN9A
PRAZOSIN	4	SCN1A, SCN2A
DILTIAZEM	4	SCN1A, SCN2A, SCN7A, SCN9A
PRENYLAMINE	4	SCN1A, SCN2A
COCAINE	4	SCN1A, SCN2A
TRIFLUOPERAZINE	4	SCN1A, SCN2A
CINNARIZINE	4	SCN1A, SCN2A
THIORIDAZINE	4	SCN1A, SCN2A
ETIDOCAINE	4	SCN1A, SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SCN9A	428	Binding:395, Functional:29, ADMET:3, Toxicity:1
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
PSMB4	171	Binding:162, ADMET:6, Functional:3
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
SCN7A	48	Binding:32, Functional:16
SCN1B	15	Binding:7, ADMET:6, Toxicity:2
GALNT3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALNT3	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN1A	149
SCN2A	203
SCN9A	428
PSMB4	171

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MEXILETINE HYDROCHLORIDE	4	SCN1A, SCN9A
BEPRIDIL	4	SCN1A, SCN2A
DIBUCAINE	4	SCN1A, SCN2A
ARTICAINE	4	SCN1A, SCN2A
BUPIVACAINE	4	SCN1A, SCN2A
IMIPRAMINE	4	SCN1A, SCN2A, SCN7A, SCN9A
DROPERIDOL	4	SCN1A, SCN2A
DICYCLOMINE	4	SCN1A, SCN2A
TETRABENAZINE	4	SCN1A, SCN2A
PHENIRAMINE	4	SCN1A, SCN2A
PRILOCAINE	4	SCN1A, SCN2A
PROPOXYCAINE	4	SCN1A, SCN2A
PROPARACAINE	4	SCN1A, SCN2A
HEXYLCAINE	4	SCN1A, SCN2A
PRAMOXINE	4	SCN1A, SCN2A
BENOXINATE	4	SCN1A, SCN2A
QUINIDINE	4	SCN1A, SCN2A
FELODIPINE	4	SCN1A, SCN2A
PHENYTOIN	4	SCN1A, SCN2A
QUININE	4	SCN1A, SCN2A
NISOLDIPINE	4	SCN1A, SCN2A
NIFEDIPINE	4	SCN1A, SCN2A, SCN7A, SCN9A
PRAZOSIN	4	SCN1A, SCN2A
DILTIAZEM	4	SCN1A, SCN2A, SCN7A, SCN9A
PRENYLAMINE	4	SCN1A, SCN2A
COCAINE	4	SCN1A, SCN2A
TRIFLUOPERAZINE	4	SCN1A, SCN2A
CINNARIZINE	4	SCN1A, SCN2A
THIORIDAZINE	4	SCN1A, SCN2A
ETIDOCAINE	4	SCN1A, SCN2A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	SCN1A, SCN2A, SCN7A, SCN9A, PSMB4
B	Phased (≥1) drug, not yet approved	1	SCN1B
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	GALNT3
E	Difficult family or no structure, no drug	5	SELENBP1, SNX27, MED27, TTC21B, SCN1A-AS1

Undrugged target profiles

6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SELENBP1	0	—
SNX27	0	—
MED27	0	—
TTC21B	0	—
GALNT3	1	—
SCN1A-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 89.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	31
PHASE3	24
PHASE2	14
PHASE1/PHASE2	10
PHASE1	6
PHASE4	4

Top trials by phase / activity

NCT	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
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
NCT04462770	PHASE3	RECRUITING	A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
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
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
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
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
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT04740476	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome
NCT05419492	PHASE1/PHASE2	RECRUITING	A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome
NCT06112275	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome (Australia Only)
NCT06283212	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
NCT06401538	PHASE2	RECRUITING	BMB-101 in Absence Epilepsy and DEE
NCT06738732	PHASE1/PHASE2	NOT_YET_RECRUITING	CBD Delivery with the A-Synaptic GT4 Transdermal Delivery System in with Dravet Syndrome And/or Lennox-Gastaut Syndrome
NCT07531745	PHASE1/PHASE2	RECRUITING	ASCEND: Safety and Tolerability of ION337 for the Treatment of Dravet Syndrome
NCT00066638	PHASE2	COMPLETED	FR901228 in Treating Patients With Relapsed or Refractory Multiple Myeloma
NCT00088855	PHASE2	COMPLETED	Bortezomib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Previously Untreated Symptomatic Multiple Myeloma
NCT00445692	PHASE2	COMPLETED	Lenalidomide, Dexamethasone, and Clarithromycin in Treating Patients Who Have Undergone Stem Cell Transplant for Multiple Myeloma
NCT00839956	PHASE2	COMPLETED	Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant
NCT01028716	PHASE2	TERMINATED	Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CANNABIDIOL	4	11
FENFLURAMINE	4	6
STIRIPENTOL	4	4
DESIPRAMINE	4	3
LENALIDOMIDE	4	3
CLOBAZAM	4	2
BORTEZOMIB	4	1
CARFILZOMIB	4	1
ELOTUZUMAB	4	1
MELPHALAN	4	1
ROMIDEPSIN	4	1
THALIDOMIDE	4	1
VERAPAMIL	4	1
VISMODEGIB	4	1
VORINOSTAT	4	1
SOTICLESTAT	3	5
ZOREVUNERSEN	2	2
BEXICASERIN	2	1
CLEMIZOLE	2	1
DEXVERAPAMIL	2	1
CHEMBL426123	0	1
CHEMBL4066465	0	1
CHEMBL5204484	0	1

Cohort genes: SCN1A, SCN1B, SCN2A, SCN7A, SCN9A, SELENBP1, SNX27, MED27, TTC21B, GALNT3, SCN1A-AS1, PSMB4
Drugs: Cannabidiol, Fenfluramine, Stiripentol, Desipramine, Lenalidomide, Clobazam, Bortezomib, Carfilzomib, Elotuzumab, Melphalan, Romidepsin, Thalidomide, Verapamil, Vismodegib, Vorinostat, Soticlestat
Associated genes: GABRA1, GABRG2, PCDH19, STXBP1