Seizures, benign familial infantile, 3

Summary

Seizures, benign familial infantile, 3 (MONDO:0011904) is a disease caused by SCN2A (GenCC Strong), with 5 cohort genes. The dominant Reactome pathway is Cardiac conduction (4 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SCN2A (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 1,972
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0002069	Bilateral tonic-clonic seizure	Frequent (30-79%)
HP:0002266	Focal clonic seizure	Frequent (30-79%)
HP:0011193	EEG with focal spikes	Frequent (30-79%)
HP:0032792	Tonic seizure	Frequent (30-79%)
HP:0032807	Neonatal seizure	Frequent (30-79%)
HP:0001350	Slurred speech	Occasional (5-29%)
HP:0002018	Nausea	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002131	Episodic ataxia	Occasional (5-29%)
HP:0002172	Postural instability	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0025401	Staring gaze	Occasional (5-29%)
HP:0001268	Mental deterioration	Very rare (<1-4%)
HP:0031491	Continuous spike and waves during slow sleep	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	seizures, benign familial infantile, 3
Mondo ID	MONDO:0011904
OMIM	607745
Orphanet	140927
DOID	DOID:0081116
UMLS	C1843140
MedGen	375105
GARD	0016521
MedDRA	10067866
Is cancer (heuristic)	no

Also known as: benign familial infantile convulsions · benign familial infantile epilepsy caused by mutation in SCN2A · benign familial neonatal-infantile seizures · benign neonatal-infantile epilepsy · BFIS3 · BFNIS · convulsions benign familial neonatal · epilepsy, benign neonatal-infantile · SCN2A benign familial infantile epilepsy · seizures, benign familial infantile, 3 · seizures, benign familial infantile, type 3

Data availability: 1,972 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › infantile epilepsy syndrome › benign partial infantile seizures › benign familial infantile epilepsy › seizures, benign familial infantile, 3

Related subtypes (4): seizures, benign familial infantile, 2, seizures, benign familial infantile, 4, seizures, benign familial infantile, 5, benign familial neonatal-infantile seizures 1

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:

232 uncertain significance, 217 likely benign, 54 pathogenic, 35 conflicting classifications of pathogenicity, 21 likely pathogenic, 18 benign/likely benign, 16 benign, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1054402	NC_000002.11:g.(?165946660)(167168266_?)del	SCN1A	Pathogenic	criteria provided, single submitter
1459193	NC_000002.11:g.(?166210682)(167168266_?)del	SCN1A	Pathogenic	criteria provided, single submitter
1000049	NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val)	SCN2A	Pathogenic	criteria provided, single submitter
1066198	NM_001040142.2(SCN2A):c.4551+1G>A	SCN2A	Pathogenic	criteria provided, single submitter
1068258	NM_001040142.2(SCN2A):c.4501A>G (p.Met1501Val)	SCN2A	Pathogenic	criteria provided, single submitter
1070304	NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr)	SCN2A	Pathogenic	criteria provided, single submitter
1071664	NM_001040142.2(SCN2A):c.718del (p.Ala240fs)	SCN2A	Pathogenic	criteria provided, single submitter
1071677	NM_001040142.2(SCN2A):c.1497del (p.Glu500fs)	SCN2A	Pathogenic	criteria provided, single submitter
1072191	NM_001040142.2(SCN2A):c.1267G>T (p.Val423Leu)	SCN2A	Pathogenic	criteria provided, single submitter
1073234	NM_001040142.2(SCN2A):c.4533dup (p.Pro1512fs)	SCN2A	Pathogenic	criteria provided, single submitter
1074161	NM_001040142.2(SCN2A):c.3782G>A (p.Trp1261Ter)	SCN2A	Pathogenic	criteria provided, single submitter
1074300	NM_001040142.2(SCN2A):c.4543C>T (p.Arg1515Ter)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1074301	NM_001040142.2(SCN2A):c.4787T>G (p.Ile1596Ser)	SCN2A	Pathogenic	criteria provided, single submitter
1180439	NM_001040142.2(SCN2A):c.986dup (p.Leu329fs)	SCN2A	Pathogenic	criteria provided, single submitter
1219256	NM_001040142.2(SCN2A):c.1729del (p.Leu577fs)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
12876	NM_001040142.2(SCN2A):c.3988C>T (p.Leu1330Phe)	SCN2A	Pathogenic	criteria provided, single submitter
12877	NM_001040142.2(SCN2A):c.4687C>G (p.Leu1563Val)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
12878	NM_001040142.2(SCN2A):c.2674G>A (p.Val892Ile)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12879	NM_001040142.2(SCN2A):c.668G>A (p.Arg223Gln)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12880	NM_001040142.2(SCN2A):c.3956G>A (p.Arg1319Gln)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
130220	NM_001040142.2(SCN2A):c.3374del (p.Glu1125fs)	SCN2A	Pathogenic	criteria provided, single submitter
1318908	NM_001040142.2(SCN2A):c.718G>T (p.Ala240Ser)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1333343	NM_001040142.2(SCN2A):c.1570C>T (p.Arg524Ter)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1342674	NM_001040142.2(SCN2A):c.4498G>A (p.Ala1500Thr)	SCN2A	Pathogenic	criteria provided, single submitter
1342682	NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)	SCN2A	Pathogenic	criteria provided, single submitter
1344839	NM_001040142.2(SCN2A):c.4913G>C (p.Arg1638Pro)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1365870	NM_001040142.2(SCN2A):c.1819_1831del (p.Arg607fs)	SCN2A	Pathogenic	criteria provided, single submitter
1381138	NM_001040142.2(SCN2A):c.3802dup (p.Val1268fs)	SCN2A	Pathogenic	criteria provided, single submitter
1403875	NM_001040142.2(SCN2A):c.1147C>T (p.Gln383Ter)	SCN2A	Pathogenic	criteria provided, single submitter
1410983	NM_001040142.2(SCN2A):c.773_776del (p.Phe257_Cys258insTer)	SCN2A	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 22 · 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
SCN2A	Strong	Autosomal dominant	seizures, benign familial infantile, 3	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
SCN3A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN3A	Orphanet:98820	Familial focal epilepsy with variable foci
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
ATP1A2	Orphanet:2131	Alternating hemiplegia of childhood
ATP1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
ATP1A2	Orphanet:569	Familial or sporadic hemiplegic migraine

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	gencc,clinvar
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
SCN3A	HGNC:10590	ENSG00000153253	Q9NY46	Sodium channel protein type 3 subunit alpha	clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
ATP1A2	HGNC:800	ENSG00000018625	P50993	Sodium/potassium-transporting ATPase subunit alpha-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of 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.
SCN3A	Sodium channel protein type 3 subunit alpha	Pore-forming subunit of Nav1.3, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in 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).
ATP1A2	Sodium/potassium-transporting ATPase subunit alpha-2	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.6

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	66.9×	2e-05
Transcription factor	1	1.6×	0.713
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN2A	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
SCN3A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
ATP1A2	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	2
middle temporal gyrus	2
cerebellar vermis	1
lateral nuclear group of thalamus	1
primary visual cortex	1
cortical plate	1
endothelial cell	1
calcaneal tendon	1
cerebellar hemisphere	1
right uterine tube	1
lateral globus pallidus	1
superior vestibular nucleus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
SCN3A	221	broad	marker	endothelial cell, cortical plate, middle temporal gyrus
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
ATP1A2	262	broad	marker	lateral globus pallidus, trigeminal ganglion, superior vestibular nucleus

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN2A	2,810
ATP1A2	2,679
SCN1A	2,287
TTC21B	1,588
SCN3A	1,454

Intra-cohort edges

A	B	Sources
ATP1A2	SCN1A	string_interaction
SCN1A	SCN2A	biogrid_interaction, string_interaction
SCN2A	SCN3A	intact

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN2A	Q99250	5
TTC21B	Q7Z4L5	3
SCN3A	Q9NY46	2
SCN1A	P35498	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP1A2	P50993	88.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cardiac conduction	4	87.0×	7e-07	SCN2A, SCN1A, SCN3A, ATP1A2
Interaction between L1 and Ankyrins	3	221.0×	1e-06	SCN2A, SCN1A, SCN3A
Phase 0 - rapid depolarisation	3	207.6×	1e-06	SCN2A, SCN1A, SCN3A
Muscle contraction	4	61.7×	1e-06	SCN2A, SCN1A, SCN3A, ATP1A2
L1CAM interactions	3	72.1×	2e-05	SCN2A, SCN1A, SCN3A
Sensory perception of taste	2	134.3×	3e-04	SCN2A, SCN3A
Sensory perception of sweet, bitter, and umami (glutamate) taste	2	111.4×	3e-04	SCN2A, SCN3A
Axon guidance	3	27.1×	3e-04	SCN2A, SCN1A, SCN3A
Nervous system development	3	25.8×	3e-04	SCN2A, SCN1A, SCN3A
Sensory Perception	2	38.1×	0.002	SCN2A, SCN3A
Developmental Biology	3	8.7×	0.006	SCN2A, SCN1A, SCN3A
Ion transport by P-type ATPases	1	41.5×	0.039	ATP1A2
Ion homeostasis	1	40.8×	0.039	ATP1A2
Intraflagellar transport	1	40.1×	0.039	TTC21B
Hedgehog ‘off’ state	1	35.7×	0.041	TTC21B
Potential therapeutics for SARS	1	22.8×	0.059	ATP1A2
Ion channel transport	1	19.2×	0.066	ATP1A2
SARS-CoV Infections	1	11.1×	0.106	ATP1A2
Viral Infection Pathways	1	6.2×	0.176	ATP1A2
Transport of small molecules	1	5.0×	0.195	ATP1A2
Infectious disease	1	5.0×	0.195	ATP1A2
Disease	1	2.6×	0.328	ATP1A2

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
sodium ion transport	4	217.4×	7e-08	SCN2A, SCN1A, SCN3A, ATP1A2
sodium ion transmembrane transport	4	162.4×	1e-07	SCN2A, SCN1A, SCN3A, ATP1A2
cardiac muscle cell action potential involved in contraction	3	421.3×	7e-07	SCN2A, SCN1A, SCN3A
membrane depolarization during action potential	2	674.1×	6e-05	SCN1A, SCN3A
neuronal action potential propagation	2	561.7×	7e-05	SCN1A, ATP1A2
neuronal action potential	2	192.6×	6e-04	SCN2A, SCN1A
olfactory cortex development	1	3370.4×	0.003	ATP1A2
intrinsic apoptotic signaling pathway in response to osmotic stress	1	1685.2×	0.004	SCN2A
regulation of glutamate uptake involved in transmission of nerve impulse	1	1685.2×	0.004	ATP1A2
negative regulation of calcium ion transmembrane transport	1	1685.2×	0.004	ATP1A2
regulation of intraciliary retrograde transport	1	1685.2×	0.004	TTC21B
negative regulation of striated muscle contraction	1	1123.5×	0.006	ATP1A2
negative regulation of heart contraction	1	842.6×	0.007	ATP1A2
protein localization to non-motile cilium	1	842.6×	0.007	TTC21B
amygdala development	1	561.7×	0.009	ATP1A2
negative regulation of eating behavior	1	561.7×	0.009	TTC21B
response to glycoside	1	481.5×	0.009	ATP1A2
regulation of striated muscle contraction	1	421.3×	0.009	ATP1A2
forebrain dorsal/ventral pattern formation	1	421.3×	0.009	TTC21B
response to potassium ion	1	421.3×	0.009	ATP1A2
positive regulation of heart contraction	1	421.3×	0.009	ATP1A2
regulation of muscle contraction	1	337.0×	0.009	ATP1A2
L-ascorbic acid metabolic process	1	306.4×	0.009	ATP1A2
locomotion	1	306.4×	0.009	ATP1A2
Bergmann glial cell differentiation	1	306.4×	0.009	TTC21B
neurotransmitter uptake	1	280.9×	0.009	ATP1A2
membrane depolarization during cardiac muscle cell action potential	1	280.9×	0.009	ATP1A2
cell communication by electrical coupling involved in cardiac conduction	1	280.9×	0.009	ATP1A2
regulation of respiratory gaseous exchange by nervous system process	1	259.3×	0.009	ATP1A2
negative regulation of cytosolic calcium ion concentration	1	259.3×	0.009	ATP1A2

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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
SCN2A	BEPRIDIL
SCN1A	MEXILETINE HYDROCHLORIDE
SCN3A	BEPRIDIL
ATP1A2	OMEPRAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SCN1A	94	4
SCN3A	93	4
ATP1A2	5	4
TTC21B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN1A, SCN2A, SCN3A
DIBUCAINE	4	SCN1A, SCN2A, SCN3A
ARTICAINE	4	SCN1A, SCN2A, SCN3A
BUPIVACAINE	4	SCN1A, SCN2A, SCN3A
IMIPRAMINE	4	SCN1A, SCN2A, SCN3A
DROPERIDOL	4	SCN1A, SCN2A, SCN3A
DICYCLOMINE	4	SCN1A, SCN2A, SCN3A
TETRABENAZINE	4	SCN1A, SCN2A, SCN3A
PHENIRAMINE	4	SCN1A, SCN2A, SCN3A
PRILOCAINE	4	SCN1A, SCN2A, SCN3A
PROPOXYCAINE	4	SCN1A, SCN2A, SCN3A
PROPARACAINE	4	SCN1A, SCN2A, SCN3A
HEXYLCAINE	4	SCN1A, SCN2A, SCN3A
PRAMOXINE	4	SCN1A, SCN2A, SCN3A
BENOXINATE	4	SCN1A, SCN2A, SCN3A
QUINIDINE	4	SCN1A, SCN2A, SCN3A
FELODIPINE	4	SCN1A, SCN2A, SCN3A
PHENYTOIN	4	SCN1A, SCN2A, SCN3A
QUININE	4	SCN1A, SCN2A, SCN3A
NISOLDIPINE	4	SCN1A, SCN2A, SCN3A
NIFEDIPINE	4	SCN1A, SCN2A, SCN3A
PRAZOSIN	4	SCN1A, SCN2A, SCN3A
DILTIAZEM	4	SCN1A, SCN2A, SCN3A
PRENYLAMINE	4	SCN1A, SCN2A, SCN3A
COCAINE	4	SCN1A, SCN2A, SCN3A
TRIFLUOPERAZINE	4	SCN1A, SCN2A, SCN3A
CINNARIZINE	4	SCN1A, SCN2A, SCN3A
THIORIDAZINE	4	SCN1A, SCN2A, SCN3A
ETIDOCAINE	4	SCN1A, SCN2A, SCN3A
CHLORPHENIRAMINE	4	SCN1A, SCN2A, SCN3A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
SCN3A	102	Binding:79, Functional:18, ADMET:4, Toxicity:1
ATP1A2	49	Binding:49

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN2A	203
SCN1A	149
SCN3A	102

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)
BEPRIDIL	4	SCN1A, SCN2A, SCN3A
DIBUCAINE	4	SCN1A, SCN2A, SCN3A
ARTICAINE	4	SCN1A, SCN2A, SCN3A
BUPIVACAINE	4	SCN1A, SCN2A, SCN3A
IMIPRAMINE	4	SCN1A, SCN2A, SCN3A
DROPERIDOL	4	SCN1A, SCN2A, SCN3A
DICYCLOMINE	4	SCN1A, SCN2A, SCN3A
TETRABENAZINE	4	SCN1A, SCN2A, SCN3A
PHENIRAMINE	4	SCN1A, SCN2A, SCN3A
PRILOCAINE	4	SCN1A, SCN2A, SCN3A
PROPOXYCAINE	4	SCN1A, SCN2A, SCN3A
PROPARACAINE	4	SCN1A, SCN2A, SCN3A
HEXYLCAINE	4	SCN1A, SCN2A, SCN3A
PRAMOXINE	4	SCN1A, SCN2A, SCN3A
BENOXINATE	4	SCN1A, SCN2A, SCN3A
QUINIDINE	4	SCN1A, SCN2A, SCN3A
FELODIPINE	4	SCN1A, SCN2A, SCN3A
PHENYTOIN	4	SCN1A, SCN2A, SCN3A
QUININE	4	SCN1A, SCN2A, SCN3A
NISOLDIPINE	4	SCN1A, SCN2A, SCN3A
NIFEDIPINE	4	SCN1A, SCN2A, SCN3A
PRAZOSIN	4	SCN1A, SCN2A, SCN3A
DILTIAZEM	4	SCN1A, SCN2A, SCN3A
PRENYLAMINE	4	SCN1A, SCN2A, SCN3A
COCAINE	4	SCN1A, SCN2A, SCN3A
TRIFLUOPERAZINE	4	SCN1A, SCN2A, SCN3A
CINNARIZINE	4	SCN1A, SCN2A, SCN3A
THIORIDAZINE	4	SCN1A, SCN2A, SCN3A
ETIDOCAINE	4	SCN1A, SCN2A, SCN3A
CHLORPHENIRAMINE	4	SCN1A, SCN2A, SCN3A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	SCN2A, SCN1A, SCN3A, ATP1A2
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	1	TTC21B

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TTC21B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.