Benign familial infantile epilepsy

Summary

Benign familial infantile epilepsy (MONDO:0017615) is a disease (an umbrella term covering 5 Mondo subtypes) with 8 cohort genes. The dominant Reactome pathway is Interaction between L1 and Ankyrins (4 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 8
• ClinVar variants: 13
• Phenotypes (HPO): 34

Clinical features

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO ID	Term	Frequency
HP:0002372	Normal interictal EEG	Very frequent (80-99%)
HP:0032807	Neonatal seizure	Very frequent (80-99%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001266	Choreoathetosis	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002104	Apnea	Frequent (30-79%)
HP:0002266	Focal clonic seizure	Frequent (30-79%)
HP:0002305	Athetosis	Frequent (30-79%)
HP:0002384	Focal impaired awareness seizure	Frequent (30-79%)
HP:0004305	Involuntary movements	Frequent (30-79%)
HP:0007166	Paroxysmal dyskinesia	Frequent (30-79%)
HP:0007334	Bilateral tonic-clonic seizure with focal onset	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0010818	Generalized tonic seizure	Frequent (30-79%)
HP:0011153	Focal motor seizure	Frequent (30-79%)
HP:0011167	Focal tonic seizure	Frequent (30-79%)
HP:0011169	Generalized clonic seizure	Frequent (30-79%)
HP:0032755	Focal impaired awareness autonomic seizure	Frequent (30-79%)
HP:0000961	Cyanosis	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002121	Generalized non-motor (absence) seizure	Occasional (5-29%)
HP:0011172	Complex febrile seizure	Occasional (5-29%)
HP:0012002	Experiential epileptic aura	Occasional (5-29%)
HP:0032678	Eyelid myoclonia seizure	Occasional (5-29%)
HP:0032823	Neonatal electro-clinical seizure with behavior arrest	Occasional (5-29%)
HP:0032906	Focal head nodding automatism seizure	Occasional (5-29%)
HP:0045084	Limb myoclonus	Occasional (5-29%)
HP:0002361	Psychomotor deterioration	Excluded (0%)
HP:0410263	Brain imaging abnormality	Excluded (0%)
HP:0002133	Status epilepticus	Very rare (<1-4%)
HP:0011171	Simple febrile seizures	Very rare (<1-4%)
HP:0011182	Interictal epileptiform activity	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	benign familial infantile epilepsy
Mondo ID	MONDO:0017615
OMIM	601764
Orphanet	306
DOID	DOID:0060169
ICD-11	1944845279
SNOMED CT	230410004
UMLS	C5575231
MedGen	1806836
GARD	0000857
Is cancer (heuristic)	no

Also known as: benign familial infantile convulsions · benign familial infantile seizures · BFIE · BFIS · seizures, benign familial infantile

Data availability: 13 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › 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

Related subtypes (4): infantile convulsions and choreoathetosis, benign non-familial infantile seizures, benign infantile seizures associated with mild gastroenteritis, benign infantile focal epilepsy with midline spikes and wave during sleep

Subtypes (5): seizures, benign familial infantile, 2, seizures, benign familial infantile, 3, 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

13 retrieved; paginated sample, class counts are floors:

7 pathogenic, 2 likely pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
1342687	NM_001040142.2(SCN2A):c.4432C>A (p.Gln1478Lys)	SCN2A	Pathogenic	no assertion criteria provided
1342691	NM_001040142.2(SCN2A):c.752T>C (p.Val251Ala)	SCN2A	Pathogenic	no assertion criteria provided
1342696	NM_001040142.2(SCN2A):c.4610T>C (p.Ile1537Thr)	SCN2A	Pathogenic	no assertion criteria provided
1342697	NM_001040142.2(SCN2A):c.1307T>C (p.Leu436Ser)	SCN2A	Pathogenic	no assertion criteria provided
1342698	NM_001040142.2(SCN2A):c.1737C>G (p.Ser579Arg)	SCN2A	Pathogenic	no assertion criteria provided
1342699	NM_001040142.2(SCN2A):c.4835C>G (p.Ala1612Gly)	SCN2A	Pathogenic	no assertion criteria provided
5196	NM_054027.6(ANKH):c.-11C>T	ANKH	Likely pathogenic	criteria provided, single submitter
1342692	NM_001040142.2(SCN2A):c.2870C>A (p.Thr957Asn)	SCN2A	Likely pathogenic	criteria provided, single submitter
1333724	NM_032776.3(JMJD1C):c.1516C>G (p.Pro506Ala)	JMJD1C	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2691440	NM_000742.4(CHRNA2):c.1350G>T (p.Lys450Asn)	CHRNA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779075	NM_000742.4(CHRNA2):c.259C>A (p.Arg87Ser)	CHRNA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 65 · Orphanet: 32 · 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
KCNQ2	Definitive	Autosomal dominant	seizures, benign familial neonatal, 1	12
PRRT2	Definitive	Autosomal dominant	infantile convulsions and choreoathetosis	18
KCNQ3	Strong	Autosomal dominant	seizures, benign familial neonatal, 2	6
SCN2A	Strong	Autosomal dominant	seizures, benign familial infantile, 3	16
SCN8A	Strong	Autosomal dominant	seizures, benign familial infantile, 5	13

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
SCN8A	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SCN8A	Orphanet:306	Self-limited infantile epilepsy
SCN8A	Orphanet:352582	Familial infantile myoclonic epilepsy
SCN8A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
PRRT2	Orphanet:306	Self-limited infantile epilepsy
PRRT2	Orphanet:36387	Genetic epilepsy with febrile seizure plus
PRRT2	Orphanet:569	Familial or sporadic hemiplegic migraine
PRRT2	Orphanet:98809	Paroxysmal kinesigenic dyskinesia
PRRT2	Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia
PRRT2	Orphanet:98811	Paroxysmal exertion-induced dyskinesia
KCNQ2	Orphanet:140927	Self-limited neonatal-infantile epilepsy
KCNQ2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
KCNQ2	Orphanet:1949	Self-limited neonatal epilepsy
KCNQ2	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNQ2	Orphanet:306	Self-limited infantile epilepsy
KCNQ2	Orphanet:439218	KCNQ2-related developmental and epileptic encephalopathy
KCNQ3	Orphanet:1949	Self-limited neonatal epilepsy
KCNQ3	Orphanet:306	Self-limited infantile epilepsy
KCNQ3	Orphanet:307	Juvenile myoclonic epilepsy
JMJD1C	Orphanet:567	22q11.2 deletion syndrome
JMJD1C	Orphanet:91352	Germinoma of the central nervous system
ANKH	Orphanet:1416	Familial calcium pyrophosphate deposition
ANKH	Orphanet:1522	Craniometaphyseal dysplasia
CHRNA2	Orphanet:98784	Sleep-related hypermotor epilepsy

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	gencc,clinvar
SCN8A	HGNC:10596	ENSG00000196876	Q9UQD0	Sodium channel protein type 8 subunit alpha	gencc
PRRT2	HGNC:30500	ENSG00000167371	Q7Z6L0	Proline-rich transmembrane protein 2	gencc
KCNQ2	HGNC:6296	ENSG00000075043	O43526	Potassium voltage-gated channel subfamily KQT member 2	gencc
KCNQ3	HGNC:6297	ENSG00000184156	O43525	Potassium voltage-gated channel subfamily KQT member 3	gencc
JMJD1C	HGNC:12313	ENSG00000171988	Q15652	Jumonji domain-containing protein 1C	clinvar
ANKH	HGNC:15492	ENSG00000154122	Q9HCJ1	Mineralization regulator ANKH	clinvar
CHRNA2	HGNC:1956	ENSG00000120903	Q15822	Neuronal acetylcholine receptor 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.
SCN8A	Sodium channel protein type 8 subunit alpha	Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradie…
PRRT2	Proline-rich transmembrane protein 2	As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system.
KCNQ2	Potassium voltage-gated channel subfamily KQT member 2	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.
KCNQ3	Potassium voltage-gated channel subfamily KQT member 3	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.
JMJD1C	Jumonji domain-containing protein 1C	Demethylates lysine in proteins, such as STAT3 or MDC1.
ANKH	Mineralization regulator ANKH	Transports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space.
CHRNA2	Neuronal acetylcholine receptor subunit alpha-2	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…

Protein-family classification

Druggable: 5 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.62

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	55.8×	1e-06
Enzyme (other)	1	1.5×	0.753
Other/Unknown	3	0.7×	0.919

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
SCN8A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
PRRT2	Other/Unknown	no		CD225/Dispanin_fam, CD225/Dispanin
KCNQ2	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ2, Ion_trans_dom
KCNQ3	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ3, Ion_trans_dom
JMJD1C	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like, KDM3A/B_DUF7030
ANKH	Other/Unknown	no		ANKH
CHRNA2	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	3
cerebellar hemisphere	3
right hemisphere of cerebellum	3
middle temporal gyrus	2
cerebellar cortex	2
cerebellar vermis	1
postcentral gyrus	1
ganglionic eminence	1
lateral nuclear group of thalamus	1
calcaneal tendon	1
inferior vagus X ganglion	1
parotid gland	1
tibia	1
cervix squamous epithelium	1
gingival epithelium	1
primordial germ cell in gonad	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
SCN8A	194	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
PRRT2	202	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
KCNQ2	183	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
KCNQ3	180	broad	marker	ganglionic eminence, lateral nuclear group of thalamus, Brodmann (1909) area 23
JMJD1C	291	ubiquitous	marker	calcaneal tendon, right hemisphere of cerebellum, cerebellar hemisphere
ANKH	273	ubiquitous	marker	tibia, parotid gland, inferior vagus X ganglion
CHRNA2	143	tissue_specific	yes	cervix squamous epithelium, primordial germ cell in gonad, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNQ2	3,388
SCN2A	2,810
KCNQ3	2,665
SCN8A	2,120
JMJD1C	1,641
PRRT2	1,545
CHRNA2	982
ANKH	850

Intra-cohort edges

A	B	Sources
KCNQ2	KCNQ3	biogrid_interaction, string_interaction
KCNQ2	PRRT2	string_interaction
KCNQ2	SCN2A	string_interaction
KCNQ2	SCN8A	string_interaction
KCNQ3	SCN2A	string_interaction
KCNQ3	SCN8A	string_interaction
PRRT2	SCN2A	string_interaction
PRRT2	SCN8A	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNQ2	O43526	39
KCNQ3	O43525	16
SCN8A	Q9UQD0	7
SCN2A	Q99250	5
JMJD1C	Q15652	3
CHRNA2	Q15822	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKH	Q9HCJ1	84.57
PRRT2	Q7Z6L0	51.86

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 8 evidence-associated genes (7 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 7 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	4	210.5×	4e-08	SCN2A, SCN8A, KCNQ2, KCNQ3
L1CAM interactions	4	68.7×	2e-06	SCN2A, SCN8A, KCNQ2, KCNQ3
Axon guidance	4	25.8×	6e-05	SCN2A, SCN8A, KCNQ2, KCNQ3
Nervous system development	4	24.5×	6e-05	SCN2A, SCN8A, KCNQ2, KCNQ3
Phase 0 - rapid depolarisation	2	98.9×	8e-04	SCN2A, SCN8A
Voltage gated Potassium channels	2	69.4×	0.001	KCNQ2, KCNQ3
Neuronal System	3	19.0×	0.001	CHRNA2, KCNQ2, KCNQ3
Developmental Biology	4	8.3×	0.002	SCN2A, SCN8A, KCNQ2, KCNQ3
Potassium Channels	2	38.4×	0.003	KCNQ2, KCNQ3
Cardiac conduction	2	31.1×	0.004	SCN2A, SCN8A
Muscle contraction	2	22.1×	0.008	SCN2A, SCN8A
Highly calcium permeable nicotinic acetylcholine receptors	1	181.3×	0.011	CHRNA2
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	148.3×	0.013	CHRNA2
Presynaptic nicotinic acetylcholine receptors	1	135.9×	0.013	CHRNA2
Acetylcholine binding and downstream events	1	116.5×	0.013	CHRNA2
Postsynaptic nicotinic acetylcholine receptors	1	116.5×	0.013	CHRNA2
Miscellaneous transport and binding events	1	62.8×	0.023	ANKH
Sensory perception of taste	1	48.0×	0.029	SCN2A
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	39.8×	0.033	SCN2A
Neurotransmitter receptors and postsynaptic signal transmission	1	14.3×	0.085	CHRNA2
Sensory Perception	1	13.6×	0.085	SCN2A
Transmission across Chemical Synapses	1	10.9×	0.100	CHRNA2
Factors involved in megakaryocyte development and platelet production	1	9.5×	0.110	JMJD1C
Hemostasis	1	5.2×	0.186	JMJD1C
Transport of small molecules	1	3.6×	0.247	ANKH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptosome assembly	1	2106.5×	0.003	KCNQ3
modulation of inhibitory postsynaptic potential	1	2106.5×	0.003	CHRNA2
regulation of action potential firing threshold	1	2106.5×	0.003	KCNQ3
negative regulation of short-term synaptic potentiation	1	2106.5×	0.003	PRRT2
cardiac muscle cell action potential involved in contraction	2	175.5×	0.003	SCN2A, SCN8A
neuronal action potential	2	120.4×	0.003	SCN2A, KCNQ3
action potential	2	89.6×	0.003	SCN8A, KCNQ2
sodium ion transport	2	68.0×	0.003	SCN2A, SCN8A
regulation of synaptic plasticity	2	64.8×	0.003	CHRNA2, KCNQ3
myelination	2	62.9×	0.003	SCN2A, SCN8A
sodium ion transmembrane transport	2	50.8×	0.004	SCN2A, SCN8A
intrinsic apoptotic signaling pathway in response to osmotic stress	1	1053.2×	0.004	SCN2A
negative regulation of SNARE complex assembly	1	1053.2×	0.004	PRRT2
substantia propria of cornea development	1	1053.2×	0.004	KCNQ3
neuron apoptotic process	2	46.3×	0.004	SCN2A, KCNQ3
inhibitory chemical synaptic transmission	1	702.2×	0.005	KCNQ3
action potential initiation	1	702.2×	0.005	KCNQ3
regulation of calcium-dependent activation of synaptic vesicle fusion	1	702.2×	0.005	PRRT2
potassium ion transmembrane transport	2	34.0×	0.005	KCNQ2, KCNQ3
inhibition of non-skeletal tissue mineralization	1	526.6×	0.006	ANKH
psychomotor behavior	1	421.3×	0.007	KCNQ3
diphosphate metabolic process	1	421.3×	0.007	ANKH
mitochondrial depolarization	1	300.9×	0.009	KCNQ3
cementum mineralization	1	300.9×	0.009	ANKH
cellular response to nicotine	1	263.3×	0.010	CHRNA2
membrane hyperpolarization	1	234.1×	0.010	KCNQ3
synaptic vesicle fusion to presynaptic active zone membrane	1	210.7×	0.010	PRRT2
response to sodium phosphate	1	210.7×	0.010	ANKH
ATP export	1	210.7×	0.010	ANKH
gene expression	2	20.0×	0.010	ANKH, KCNQ3

Therapeutics

Drug target analysis

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

Druggability breadth: 6 of 8 evidence-associated genes (75%) 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
SCN8A	IMIPRAMINE
KCNQ2	FLUPIRTINE
KCNQ3	FLUPIRTINE
CHRNA2	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SCN8A	25	4
KCNQ2	4	4
CHRNA2	4	4
KCNQ3	3	4
PRRT2	0	0
JMJD1C	0	0
ANKH	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A, SCN8A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A, SCN8A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A, SCN8A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	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
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
SCN8A	173	Binding:148, Functional:16, ADMET:7, Toxicity:2
KCNQ2	145	Binding:136, Functional:7, ADMET:1, Toxicity:1
KCNQ3	97	Binding:91, Functional:4, ADMET:1, Toxicity:1
CHRNA2	40	Binding:37, Functional:2, ADMET:1
JMJD1C	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
JMJD1C	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN2A	203
SCN8A	173
KCNQ2	145

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A, SCN8A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A, SCN8A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A, SCN8A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	SCN2A, SCN8A, KCNQ2, KCNQ3, CHRNA2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	JMJD1C
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PRRT2, ANKH

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)
PRRT2	0	SCN2A
JMJD1C	2	—
ANKH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.