Generalized epilepsy with febrile seizures plus, type 7

Summary

Generalized epilepsy with febrile seizures plus, type 7 (MONDO:0013470) is a disease caused by SCN9A (GenCC Strong), with 6 cohort genes. The dominant Reactome pathway is Interaction between L1 and Ankyrins (3 cohort genes).

At a glance

• Causal gene: SCN9A (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 2,680

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	generalized epilepsy with febrile seizures plus, type 7
Mondo ID	MONDO:0013470
MeSH	C567827
OMIM	613863
DOID	DOID:0111295
UMLS	C2751778
MedGen	416630
GARD	0018665
Is cancer (heuristic)	no

Also known as: Gefs+, type 7 · GEFSP7 · generalized epilepsy with febrile seizures plus, type 7

Data availability: 2,680 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › hereditary generalized epilepsy › generalized epilepsy with febrile seizures plus › generalized epilepsy with febrile seizures plus, type 7

Related subtypes (9): generalized epilepsy with febrile seizures plus, type 1, generalized epilepsy with febrile seizures plus, type 2, febrile seizures, familial, 8, generalized epilepsy with febrile seizures plus, type 4, generalized epilepsy with febrile seizures plus, type 6, generalized epilepsy with febrile seizures plus, type 8, generalized epilepsy with febrile seizures plus, type 9, generalized epilepsy with febrile seizures plus, type 10, generalized epilepsy with febrile seizures plus, type 12

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:

396 uncertain significance, 139 likely benign, 23 pathogenic, 16 conflicting classifications of pathogenicity, 11 benign, 10 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1054402	NC_000002.11:g.(?165946660)(167168266_?)del	SCN1A	Pathogenic	criteria provided, single submitter
1069309	NM_001365536.1(SCN9A):c.5004T>A (p.Tyr1668Ter)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1354382	NM_001365536.1(SCN9A):c.1497del (p.Lys499fs)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1392241	NM_001365536.1(SCN9A):c.1678_1679insCT (p.Arg560fs)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1415855	NM_001365536.1(SCN9A):c.915C>A (p.Tyr305Ter)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1430446	NM_001365536.1(SCN9A):c.3818del (p.Thr1272_Leu1273insTer)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1441374	NM_001365536.1(SCN9A):c.3096del (p.Lys1033fs)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1450127	NM_001365536.1(SCN9A):c.1502C>A (p.Ser501Ter)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1450897	NM_001365536.1(SCN9A):c.2507C>A (p.Ser836Ter)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1451235	NM_001365536.1(SCN9A):c.5008A>T (p.Lys1670Ter)	SCN1A-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454265	NM_001365536.1(SCN9A):c.5004T>G (p.Tyr1668Ter)	SCN1A-AS1	Pathogenic	criteria provided, single submitter
1024965	NM_001365536.1(SCN9A):c.2599G>C (p.Gly867Arg)	SCN9A	Pathogenic	criteria provided, single submitter
1068510	NM_001365536.1(SCN9A):c.2204del (p.Lys735fs)	SCN9A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068637	NM_001365536.1(SCN9A):c.5100G>A (p.Trp1700Ter)	SCN9A	Pathogenic	criteria provided, single submitter
1070653	NM_001365536.1(SCN9A):c.2984_2985insC (p.Ile995_Lys996insTer)	SCN9A	Pathogenic	criteria provided, single submitter
1070796	NM_001365536.1(SCN9A):c.4740_4743dup (p.Asp1582delinsPheTer)	SCN9A	Pathogenic	criteria provided, single submitter
1074563	NC_000002.11:g.(?167055172)(167060984_?)del	SCN9A	Pathogenic	criteria provided, single submitter
1075008	NM_001365536.1(SCN9A):c.116del (p.Lys39fs)	SCN9A	Pathogenic	criteria provided, single submitter
1075155	NM_001365536.1(SCN9A):c.4855C>T (p.Arg1619Ter)	SCN9A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075796	NM_001365536.1(SCN9A):c.2667dup (p.Lys890Ter)	SCN9A	Pathogenic	criteria provided, single submitter
1076717	NM_001365536.1(SCN9A):c.2409T>A (p.Tyr803Ter)	SCN9A	Pathogenic	criteria provided, single submitter
1076959	NM_001365536.1(SCN9A):c.3801+1G>A	SCN9A	Pathogenic	criteria provided, single submitter
1355824	NM_001365536.1(SCN9A):c.3183_3199del (p.Phe1062fs)	SCN9A	Pathogenic	criteria provided, single submitter
1378654	NM_001365536.1(SCN9A):c.4195_4196del (p.Leu1399fs)	SCN9A	Pathogenic	criteria provided, single submitter
1448916	NM_001365536.1(SCN9A):c.4828C>T (p.Arg1610Ter)	SCN9A	Pathogenic	criteria provided, single submitter
1451242	NM_001365536.1(SCN9A):c.3352-1G>A	SCN9A	Pathogenic	criteria provided, single submitter
1067970	NM_001365536.1(SCN9A):c.4398+2T>C	SCN1A-AS1	Likely pathogenic	criteria provided, single submitter
1466702	NM_001365536.1(SCN9A):c.2518-1G>T	SCN1A-AS1	Likely pathogenic	criteria provided, single submitter
1496453	NM_001365536.1(SCN9A):c.3924+1G>C	SCN1A-AS1	Likely pathogenic	criteria provided, single submitter
1500840	NM_001365536.1(SCN9A):c.3928G>A (p.Val1310Ile)	SCN1A-AS1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 24 · 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
SCN9A	Strong	Autosomal dominant	generalized epilepsy with febrile seizures plus, type 7	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
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
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN9A	HGNC:10597	ENSG00000169432	Q15858	Sodium channel protein type 9 subunit alpha	gencc,clinvar
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
CSRNP3	HGNC:30729	ENSG00000178662	Q8WYN3	Cysteine/serine-rich nuclear protein 3	clinvar
SCN1A-AS1	HGNC:54069	ENSG00000236107		SCN1A and SCN9A antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
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).
CSRNP3	Cysteine/serine-rich nuclear protein 3	Binds to the consensus sequence 5’-AGAGTG-3’ and has transcriptional activator activity.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 3 · 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	3	55.8×	3e-05
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN9A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
CSRNP3	Other/Unknown	no		Cys/Ser-rich_nuc_prot, CSRNP_N
SCN1A-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	3
sural nerve	2
middle temporal gyrus	2
dorsal root ganglion	1
stromal cell of endometrium	1
lateral nuclear group of thalamus	1
primary visual cortex	1
cerebellar vermis	1
calcaneal tendon	1
cerebellar hemisphere	1
right uterine tube	1
entorhinal cortex	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN9A	187	ubiquitous	marker	sural nerve, dorsal root ganglion, stromal cell of endometrium
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
CSRNP3	226	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, entorhinal cortex
SCN1A-AS1	129	tissue_specific	marker	sural nerve, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN2A	2,810
SCN1A	2,287
TTC21B	1,588
SCN9A	1,575
CSRNP3	486
SCN1A-AS1	0

Intra-cohort edges

A	B	Sources
SCN1A	SCN2A	biogrid_interaction, string_interaction
SCN2A	SCN9A	intact

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN9A	Q15858	43
SCN2A	Q99250	5
TTC21B	Q7Z4L5	3
SCN1A	P35498	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CSRNP3	Q8WYN3	60.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 6 evidence-associated genes (4 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 4 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	3	276.3×	6e-07	SCN9A, SCN1A, SCN2A
Phase 0 - rapid depolarisation	3	259.6×	6e-07	SCN9A, SCN1A, SCN2A
L1CAM interactions	3	90.2×	1e-05	SCN9A, SCN1A, SCN2A
Cardiac conduction	3	81.6×	1e-05	SCN9A, SCN1A, SCN2A
Muscle contraction	3	57.9×	2e-05	SCN9A, SCN1A, SCN2A
Sensory perception of taste	2	167.9×	8e-05	SCN9A, SCN2A
Axon guidance	3	33.9×	8e-05	SCN9A, SCN1A, SCN2A
Nervous system development	3	32.2×	8e-05	SCN9A, SCN1A, SCN2A
Sensory perception of sweet, bitter, and umami (glutamate) taste	2	139.3×	1e-04	SCN9A, SCN2A
Sensory Perception	2	47.6×	8e-04	SCN9A, SCN2A
Developmental Biology	3	10.8×	0.001	SCN9A, SCN1A, SCN2A
Intraflagellar transport	1	50.1×	0.021	TTC21B
Hedgehog ‘off’ state	1	44.6×	0.022	TTC21B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	3	421.3×	1e-06	SCN9A, SCN1A, SCN2A
neuronal action potential	3	288.9×	2e-06	SCN9A, SCN1A, SCN2A
sodium ion transmembrane transport	3	121.8×	2e-05	SCN9A, SCN1A, SCN2A
sodium ion transport	2	108.7×	0.001	SCN1A, SCN2A
action potential propagation	1	3370.4×	0.003	SCN9A
intrinsic apoptotic signaling pathway in response to osmotic stress	1	1685.2×	0.004	SCN2A
regulation of intraciliary retrograde transport	1	1685.2×	0.004	TTC21B
protein localization to non-motile cilium	1	842.6×	0.007	TTC21B
detection of mechanical stimulus involved in sensory perception	1	561.7×	0.008	SCN9A
negative regulation of eating behavior	1	561.7×	0.008	TTC21B
forebrain dorsal/ventral pattern formation	1	421.3×	0.010	TTC21B
membrane depolarization during action potential	1	337.0×	0.011	SCN1A
Bergmann glial cell differentiation	1	306.4×	0.011	TTC21B
neuronal action potential propagation	1	280.9×	0.011	SCN1A
intraciliary retrograde transport	1	224.7×	0.012	TTC21B
detection of mechanical stimulus involved in sensory perception of pain	1	224.7×	0.012	SCN1A
cerebellar Purkinje cell differentiation	1	210.7×	0.012	TTC21B
neuromuscular process controlling posture	1	210.7×	0.012	SCN1A
nerve development	1	187.2×	0.012	SCN1A
behavioral response to pain	1	177.4×	0.012	SCN9A
ventricular system development	1	168.5×	0.012	TTC21B
detection of temperature stimulus involved in sensory perception of pain	1	168.5×	0.012	SCN9A
regulation of smoothened signaling pathway	1	124.8×	0.016	TTC21B
adult walking behavior	1	99.1×	0.019	SCN1A
determination of adult lifespan	1	86.4×	0.021	SCN1A
protein localization to cilium	1	80.2×	0.021	TTC21B
sensory perception of pain	1	74.9×	0.022	SCN9A
myelination	1	50.3×	0.032	SCN2A
circadian rhythm	1	48.9×	0.032	SCN9A
response to toxic substance	1	42.1×	0.035	SCN9A

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 6 evidence-associated genes (50%) 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
SCN9A	IMIPRAMINE
SCN1A	MEXILETINE HYDROCHLORIDE
SCN2A	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SCN1A	94	4
SCN9A	36	4
TTC21B	0	0
CSRNP3	0	0
SCN1A-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IMIPRAMINE	4	SCN1A, SCN2A, SCN9A
SERTINDOLE	4	SCN1A, SCN2A, SCN9A
PIMOZIDE	4	SCN1A, SCN2A, SCN9A
NIFEDIPINE	4	SCN1A, SCN2A, SCN9A
DILTIAZEM	4	SCN1A, SCN2A, SCN9A
MIBEFRADIL	4	SCN1A, SCN2A, SCN9A
HALOPERIDOL	4	SCN1A, SCN2A, SCN9A
MEXILETINE	4	SCN1A, SCN2A, SCN9A
AMITRIPTYLINE	4	SCN1A, SCN2A, SCN9A
AMIODARONE	4	SCN1A, SCN2A, SCN9A
CHLORPROMAZINE	4	SCN1A, SCN2A, SCN9A
CARBAMAZEPINE	4	SCN9A
MEXILETINE HYDROCHLORIDE	4	SCN1A, SCN9A
CANNABIDIOL	4	SCN9A
SAFINAMIDE	4	SCN9A
LACOSAMIDE	4	SCN9A
TETRACAINE	4	SCN1A, SCN2A, SCN9A
LAMOTRIGINE	4	SCN2A, SCN9A
RILUZOLE	4	SCN2A, SCN9A
LIDOCAINE	4	SCN9A
BEPRIDIL	4	SCN1A, SCN2A
DIBUCAINE	4	SCN1A, SCN2A
ARTICAINE	4	SCN1A, SCN2A
BUPIVACAINE	4	SCN1A, SCN2A
DROPERIDOL	4	SCN1A, SCN2A
DICYCLOMINE	4	SCN1A, SCN2A
TETRABENAZINE	4	SCN1A, SCN2A
PHENIRAMINE	4	SCN1A, SCN2A
PRILOCAINE	4	SCN1A, SCN2A
PROPOXYCAINE	4	SCN1A, SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN9A	428
SCN1A	149
SCN2A	203

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
IMIPRAMINE	4	SCN1A, SCN2A, SCN9A
SERTINDOLE	4	SCN1A, SCN2A, SCN9A
PIMOZIDE	4	SCN1A, SCN2A, SCN9A
NIFEDIPINE	4	SCN1A, SCN2A, SCN9A
DILTIAZEM	4	SCN1A, SCN2A, SCN9A
MIBEFRADIL	4	SCN1A, SCN2A, SCN9A
HALOPERIDOL	4	SCN1A, SCN2A, SCN9A
MEXILETINE	4	SCN1A, SCN2A, SCN9A
AMITRIPTYLINE	4	SCN1A, SCN2A, SCN9A
AMIODARONE	4	SCN1A, SCN2A, SCN9A
CHLORPROMAZINE	4	SCN1A, SCN2A, SCN9A
CARBAMAZEPINE	4	SCN9A
MEXILETINE HYDROCHLORIDE	4	SCN1A, SCN9A
CANNABIDIOL	4	SCN9A
SAFINAMIDE	4	SCN9A
LACOSAMIDE	4	SCN9A
TETRACAINE	4	SCN1A, SCN2A, SCN9A
LAMOTRIGINE	4	SCN2A, SCN9A
RILUZOLE	4	SCN2A, SCN9A
LIDOCAINE	4	SCN9A
BEPRIDIL	4	SCN1A, SCN2A
DIBUCAINE	4	SCN1A, SCN2A
ARTICAINE	4	SCN1A, SCN2A
BUPIVACAINE	4	SCN1A, SCN2A
DROPERIDOL	4	SCN1A, SCN2A
DICYCLOMINE	4	SCN1A, SCN2A
TETRABENAZINE	4	SCN1A, SCN2A
PHENIRAMINE	4	SCN1A, SCN2A
PRILOCAINE	4	SCN1A, SCN2A
PROPOXYCAINE	4	SCN1A, SCN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SCN9A, SCN1A, SCN2A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	TTC21B, CSRNP3, SCN1A-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TTC21B	0	—
CSRNP3	0	—
SCN1A-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.