Self-limited epilepsy with centrotemporal spikes

Summary

Self-limited epilepsy with centrotemporal spikes (MONDO:0007295) is a disease with 36 cohort genes and 12 clinical trials. The dominant Reactome pathway is Interaction between L1 and Ankyrins (6 cohort genes). Top therapeutic interventions include carbamazepine, levetiracetam, and etiracetam.

At a glance

• Prevalence: 1-5 / 10 000 (Sweden) [Orphanet-validated]
• Cohort genes: 36
• ClinVar variants: 112
• Phenotypes (HPO): 21
• Clinical trials: 12

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-5 / 10 000	20	Sweden	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0012557	EEG with centrotemporal focal spike waves	Very frequent (80-99%)
HP:0002307	Drooling	Frequent (30-79%)
HP:0007332	Focal hemifacial clonic seizure	Frequent (30-79%)
HP:0007334	Bilateral tonic-clonic seizure with focal onset	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0009088	Speech articulation difficulties	Frequent (30-79%)
HP:0010535	Sleep apnea	Frequent (30-79%)
HP:0025425	Laryngospasm	Frequent (30-79%)
HP:0000712	Emotional lability	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000736	Short attention span	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0002076	Migraine	Occasional (5-29%)
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0006889	Intellectual disability, borderline	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0012534	Dysesthesia	Occasional (5-29%)
HP:0001326	EEG with irregular generalized spike and wave complexes	Very rare (<1-4%)
HP:0007270	Atypical absence seizure	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	self-limited epilepsy with centrotemporal spikes
Mondo ID	MONDO:0007295
OMIM	117100
Orphanet	1945
DOID	DOID:3329
ICD-11	1046279423
NCIT	C116538
SNOMED CT	44145005
UMLS	C0376532
MedGen	138210
GARD	0010287
Is cancer (heuristic)	no

Also known as: BCECTS · BECRS · BECTS · benign childhood epilepsy with centrotemporal spikes · benign epilepsy of childhood with centrotemporal spikes · benign epilepsy of childhood with centrotemporal spikes (BECCT) · benign epilepsy with centro-temporal spikes (BECTS) · benign epilepsy with centrotemporal spikes · benign familial epilepsy of childhood with rolandic spikes · benign Rolandic epilepsy · benign Rolandic epilepsy (BRE) · benign Rolandic epilepsy of childhood (BREC) · BRE · centralopathic epilepsy · centrotemporal epilepsy · centrotemporal epilepsy, isolated cases · childhood epilepsy with centrotemporal spikes · Rolandic epilepsy · temporal-central focal epilepsy

Data availability: 112 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › focal epilepsy › familial partial epilepsy › self-limited epilepsy with centrotemporal spikes

Related subtypes (6): familial sleep-related hypermotor epilepsy, temporal lobe epilepsy, autosomal dominant epilepsy with auditory features, generalized epilepsy-paroxysmal dyskinesia syndrome, familial focal epilepsy with variable foci, mesial temporal lobe epilepsy with hippocampal sclerosis

Subtypes (1): GRIN2A-related self-limited epilepsy with centrotemporal spikes

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

112 retrieved; paginated sample, class counts are floors:

32 uncertain significance, 28 conflicting classifications of pathogenicity, 27 pathogenic, 9 benign/likely benign, 4 benign, 4 likely benign, 4 pathogenic/likely pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
433117	NM_001271.4(CHD2):c.149G>A (p.Gly50Asp)	CHD2	Pathogenic	no assertion criteria provided
433118	NM_001271.4(CHD2):c.4829C>T (p.Ala1610Val)	CHD2	Pathogenic	no assertion criteria provided
8396	NM_000100.4(CSTB):c.202C>T (p.Arg68Ter)	CSTB	Pathogenic	criteria provided, multiple submitters, no conflicts
264739	NM_001242896.3(DEPDC5):c.3444del (p.Ile1148fs)	DEPDC5	Pathogenic	no assertion criteria provided
433141	NM_001242896.3(DEPDC5):c.-57G>C	DEPDC5	Pathogenic	no assertion criteria provided
433143	NM_001242896.3(DEPDC5):c.2492_2493insAGA (p.Ser831delinsArgAsp)	DEPDC5	Pathogenic	no assertion criteria provided
433103	NM_005670.4(EPM2A):c.314A>G (p.His105Arg)	EPM2A	Pathogenic	no assertion criteria provided
433102	NM_198904.4(GABRG2):c.769G>A (p.Gly257Arg)	GABRG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60708	NM_198904.4(GABRG2):c.968G>A (p.Arg323Gln)	GABRG2	Pathogenic	criteria provided, multiple submitters, no conflicts
433116	NM_007327.4(GRIN1):c.2504T>C (p.Ile835Thr)	GRIN1	Pathogenic	no assertion criteria provided
433123	NM_001134407.3(GRIN2A):c.2200G>C (p.Val734Leu)	GRIN2A	Pathogenic	no assertion criteria provided
433124	NM_001134407.3(GRIN2A):c.2179G>A (p.Ala727Thr)	GRIN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433126	NM_001134407.3(GRIN2A):c.1639_1641del (p.Ser547del)	GRIN2A	Pathogenic	no assertion criteria provided
433127	NM_001134407.3(GRIN2A):c.1306T>C (p.Cys436Arg)	GRIN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433128	NM_001134407.3(GRIN2A):c.1007+1G>T	GRIN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
88727	NM_001134407.3(GRIN2A):c.1007+1G>A	GRIN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433110	NM_004519.4(KCNQ3):c.1142C>T (p.Ala381Val)	KCNQ3	Pathogenic	no assertion criteria provided
433140	NM_001320643.3(LOC102724428):c.379C>T (p.Arg127Trp)	LOC102724428	Pathogenic	no assertion criteria provided
433139	NM_015192.4(PLCB1):c.3382C>T (p.His1128Tyr)	PLCB1	Pathogenic	no assertion criteria provided
433136	NM_001350451.2(RBFOX3):c.1002C>A (p.Tyr334Ter)	RBFOX3	Pathogenic	no assertion criteria provided
433105	NM_005045.4(RELN):c.9976C>T (p.Arg3326Ter)	RELN	Pathogenic	criteria provided, single submitter
433106	NM_005045.4(RELN):c.5791A>G (p.Asn1931Asp)	RELN	Pathogenic	no assertion criteria provided
433097	NM_001040142.2(SCN2A):c.2182T>C (p.Cys728Arg)	SCN2A	Pathogenic	no assertion criteria provided
433085	NM_006516.4(SLC2A1):c.1010A>T (p.His337Leu)	SLC2A1	Pathogenic	no assertion criteria provided
433114	NM_001130438.3(SPTAN1):c.4852G>A (p.Gly1618Ser)	SPTAN1	Pathogenic	no assertion criteria provided
433115	NM_001130438.3(SPTAN1):c.6854A>G (p.Asn2285Ser)	SPTAN1	Pathogenic	no assertion criteria provided
433133	NM_001003787.4(STRADA):c.403G>A (p.Ala135Thr)	STRADA	Pathogenic	no assertion criteria provided
433134	NM_001003787.4(STRADA):c.190C>T (p.Pro64Ser)	STRADA	Pathogenic	no assertion criteria provided
433086	NM_001365999.1(SZT2):c.105C>G (p.Phe35Leu)	SZT2	Pathogenic	no assertion criteria provided
433092	NM_001365999.1(SZT2):c.5938G>A (p.Val1980Met)	SZT2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 29 · Orphanet: 102 · 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
GABRG2	Definitive	Autosomal dominant	epilepsy	11
GRIN2A	Supportive	Autosomal dominant	rolandic epilepsy-speech dyspraxia syndrome	12
BRWD3	Limited	Autosomal dominant	self-limited epilepsy with centrotemporal spikes	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GABRG2	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GABRG2	Orphanet:33069	Dravet syndrome
GABRG2	Orphanet:36387	Genetic epilepsy with febrile seizure plus
GABRG2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
GABRG2	Orphanet:64280	Childhood absence epilepsy
GRIN2A	Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome
GRIN2A	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GRIN2A	Orphanet:289266	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation
GRIN2A	Orphanet:725	Developmental and epileptic encephalopathy with spike-wave activation in sleep
GRIN2A	Orphanet:98818	Landau-Kleffner syndrome
BRWD3	Orphanet:528084	Non-specific syndromic intellectual disability
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
SLC2A1	Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin
SLC2A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SLC2A1	Orphanet:2131	Alternating hemiplegia of childhood
SLC2A1	Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1	Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome
SLC2A1	Orphanet:86911	Epilepsy with myoclonic absences
SLC2A1	Orphanet:98811	Paroxysmal exertion-induced dyskinesia
SLC6A1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SLC6A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SPTAN1	Orphanet:697160	Infantile epileptic spasms syndrome
WWOX	Orphanet:251510	46,XY partial gonadal dysgenesis

Cohort genes → proteins

36 cohort genes, 34 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	36

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GABRG2	HGNC:4087	ENSG00000113327	P18507	Gamma-aminobutyric acid receptor subunit gamma-2	gencc,clinvar
GRIN2A	HGNC:4585	ENSG00000183454	Q12879	Glutamate receptor ionotropic, NMDA 2A	gencc,clinvar
BRWD3	HGNC:17342	ENSG00000165288	Q6RI45	Bromodomain and WD repeat-containing protein 3	gencc
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	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
SCN9A	HGNC:10597	ENSG00000169432	Q15858	Sodium channel protein type 9 subunit alpha	clinvar
SLC2A1	HGNC:11005	ENSG00000117394	P11166	Solute carrier family 2, facilitated glucose transporter member 1	clinvar
SLC6A1	HGNC:11042	ENSG00000157103	P30531	Sodium- and chloride-dependent GABA transporter 1	clinvar
SPTAN1	HGNC:11273	ENSG00000197694	Q13813	Spectrin alpha chain, non-erythrocytic 1	clinvar
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	clinvar
CNTNAP2	HGNC:13830	ENSG00000174469	Q9UHC6	Contactin-associated protein-like 2	clinvar
PCDH19	HGNC:14270	ENSG00000165194	Q8TAB3	Protocadherin-19	clinvar
PLCB1	HGNC:15917	ENSG00000182621	Q9NQ66	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	clinvar
SCARB2	HGNC:1665	ENSG00000138760	Q14108	Lysosome membrane protein 2	clinvar
PRICKLE1	HGNC:17019	ENSG00000139174	Q96MT3	Prickle-like protein 1	clinvar
CPA6	HGNC:17245	ENSG00000165078	Q8N4T0	Carboxypeptidase A6	clinvar
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	clinvar
DEPDC5	HGNC:18423	ENSG00000100150	O75140	GATOR1 complex protein DEPDC5	clinvar
IER3IP1	HGNC:18550	ENSG00000134049	Q9Y5U9	Immediate early response 3-interacting protein 1	clinvar
KCNT1	HGNC:18865	ENSG00000107147	Q5JUK3	Potassium channel subfamily T member 1	clinvar
CHD2	HGNC:1917	ENSG00000173575	O14647	ATP-dependent chromatin remodeler CHD2	clinvar
PRICKLE2	HGNC:20340	ENSG00000163637	Q7Z3G6	Prickle-like protein 2	clinvar
CSTB	HGNC:2482	ENSG00000160213	P04080	Cystatin-B	clinvar
RBFOX3	HGNC:27097	ENSG00000167281	A6NFN3	RNA binding protein fox-1 homolog 3	clinvar
SZT2	HGNC:29040	ENSG00000198198	Q5T011	KICSTOR complex protein SZT2	clinvar
TBC1D24	HGNC:29203	ENSG00000162065	Q9ULP9	TBC1 domain family member 24	clinvar
STRADA	HGNC:30172	ENSG00000266173	Q7RTN6	STE20-related kinase adapter protein alpha	clinvar
EPM2A	HGNC:3413	ENSG00000112425	B3EWF7	Laforin, isoform 9	clinvar
GRIN1	HGNC:4584	ENSG00000176884	Q05586	Glutamate receptor ionotropic, NMDA 1	clinvar
SCN1A-AS1	HGNC:54069	ENSG00000236107		SCN1A and SCN9A antisense RNA 1	clinvar
ARFGEF1-DT	HGNC:55237	ENSG00000271966		ARFGEF1 divergent transcript	clinvar
KCNQ3	HGNC:6297	ENSG00000184156	O43525	Potassium voltage-gated channel subfamily KQT member 3	clinvar
MAF	HGNC:6776	ENSG00000178573	O75444	Transcription factor Maf	clinvar
ASAH1	HGNC:735	ENSG00000104763	Q13510	Acid ceramidase	clinvar
RELN	HGNC:9957	ENSG00000189056	P78509	Reelin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GABRG2	Gamma-aminobutyric acid receptor subunit gamma-2	Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
GRIN2A	Glutamate receptor ionotropic, NMDA 2A	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
BRWD3	Bromodomain and WD repeat-containing protein 3	Plays a role in the regulation of cell morphology and cytoskeletal organization.
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.
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.
SLC2A1	Solute carrier family 2, facilitated glucose transporter member 1	Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.
SLC6A1	Sodium- and chloride-dependent GABA transporter 1	Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse.
SPTAN1	Spectrin alpha chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
CNTNAP2	Contactin-associated protein-like 2	Required for gap junction formation.
PCDH19	Protocadherin-19	Calcium-dependent cell-adhesion protein.
PLCB1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors.
SCARB2	Lysosome membrane protein 2	Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting.
PRICKLE1	Prickle-like protein 1	Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.
CPA6	Carboxypeptidase A6	May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
DEPDC5	GATOR1 complex protein DEPDC5	As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway.
IER3IP1	Immediate early response 3-interacting protein 1	Regulator of endoplasmic reticulum secretion that acts as a key determinant of brain size.
KCNT1	Potassium channel subfamily T member 1	Sodium-activated K(+) channel.
CHD2	ATP-dependent chromatin remodeler CHD2	ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3.
PRICKLE2	Prickle-like protein 2	Is involved in the organization and maintenance of axon initial segment (AIS) architecture, likely cooperating with IGSF9B to regulate ANK3/ANKG localization to AIS.
CSTB	Cystatin-B	This is an intracellular thiol proteinase inhibitor.
RBFOX3	RNA binding protein fox-1 homolog 3	Pre-mRNA alternative splicing regulator.
SZT2	KICSTOR complex protein SZT2	As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway.
TBC1D24	TBC1 domain family member 24	May act as a GTPase-activating protein for Rab family protein(s).
STRADA	STE20-related kinase adapter protein alpha	Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1.
GRIN1	Glutamate receptor ionotropic, NMDA 1	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
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.
MAF	Transcription factor Maf	Acts as a transcriptional activator or repressor.
ASAH1	Acid ceramidase	Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH.
RELN	Reelin	Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

Protein-family classification

Druggable: 12 · Difficult: 6 · Unknown: 18 · Druggable fraction: 0.33

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	5	15.5×	2e-04
Phosphatase	1	2.3×	0.828
Transporter	1	2.2×	0.828
Scaffold/PPI	3	1.4×	0.828
Protease	1	1.0×	0.828
Other/Unknown	18	0.9×	0.828
Antibody/Immunoglobulin	1	0.8×	0.828
Kinase	1	0.8×	0.828
Transcription factor	3	0.7×	0.828
Enzyme (other)	2	0.7×	0.828

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GABRG2	Other/Unknown	no		GABRG-1/4, GABBAg2_rcpt, GABAA/Glycine_rcpt
GRIN2A	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
BRWD3	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
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
SCN9A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SLC2A1	Transporter	yes		Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like
SLC6A1	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_GABA_GAT1, SNS_sf
SPTAN1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
CNTNAP2	Other/Unknown	no		FA58C, EGF, Laminin_G
PCDH19	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf
PLCB1	Enzyme (other)	yes	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam
SCARB2	Other/Unknown	no		CD36_fam, LimpII
PRICKLE1	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
CPA6	Protease	yes		Peptidase_M14, M14A_act_pep, CPAH
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
DEPDC5	Other/Unknown	no		DEP_dom, IML1, WH-like_DNA-bd_sf
IER3IP1	Other/Unknown	no		Yos1
KCNT1	Ion channel	yes		RCK_N, K_chnl_BK_asu, K_chnl_dom
CHD2	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
PRICKLE2	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
CSTB	Other/Unknown	no		Cystatin_dom, Prot_inh_stefin, Prot_inh_cystat_CS
RBFOX3	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
SZT2	Other/Unknown	no		SZT2
TBC1D24	Other/Unknown	no		Rab-GAP-TBC_dom, TLDc_dom, Rab-GAP_TBC_sf
STRADA	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, STRAD_A/B-like
EPM2A	Phosphatase	yes	3.1.3.16	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, CBM20
GRIN1	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
SCN1A-AS1	Other/Unknown	no
ARFGEF1-DT	Other/Unknown	no
KCNQ3	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ3, Ion_trans_dom
MAF	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
ASAH1	Enzyme (other)	yes	3.5.1.23	Acid_ceramidase-like, Acid_ceramidase_N, CBAH/NAAA_C
RELN	Other/Unknown	no		EGF, Reeler_dom, EGF_extracell

Expression context

Cohort genes with no expression data: 0.

35 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)	36
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	8
middle temporal gyrus	6
right hemisphere of cerebellum	5
sural nerve	5
lateral nuclear group of thalamus	4
cerebellar hemisphere	4
superior frontal gyrus	3
cerebellar vermis	3
cerebellar cortex	3
colonic epithelium	3
endothelial cell	2
calcaneal tendon	2
tendon of biceps brachii	2
primary visual cortex	2
cerebellum	2
parotid gland	2
cortical plate	2
germinal epithelium of ovary	2
buccal mucosa cell	2
ganglionic eminence	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GABRG2	174	tissue_specific	marker	middle temporal gyrus, Brodmann (1909) area 23, superior frontal gyrus
GRIN2A	199	broad	marker	Brodmann (1909) area 23, endothelial cell, middle temporal gyrus
BRWD3	223	ubiquitous	marker	tendon of biceps brachii, epithelial cell of pancreas, calcaneal tendon
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
SCN9A	187	ubiquitous	marker	sural nerve, dorsal root ganglion, stromal cell of endometrium
SLC2A1	250	ubiquitous	marker	tibial nerve, sural nerve, skin of abdomen
SLC6A1	207	broad	marker	lateral nuclear group of thalamus, lateral globus pallidus, cerebellar vermis
SPTAN1	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
CNTNAP2	127	broad	marker	corpus callosum, superior frontal gyrus, C1 segment of cervical spinal cord
PCDH19	175	broad	marker	cortical plate, entorhinal cortex, middle temporal gyrus
PLCB1	278	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, superior frontal gyrus
SCARB2	298	ubiquitous	marker	inferior vagus X ganglion, subthalamic nucleus, germinal epithelium of ovary
PRICKLE1	243	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral nuclear group of thalamus
CPA6	103	broad	marker	buccal mucosa cell, mucosa of transverse colon, urethra
RBFOX1	220	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cortical plate
DEPDC5	236	ubiquitous	marker	paraflocculus, frontal pole, middle frontal gyrus
IER3IP1	262	ubiquitous	marker	oocyte, secondary oocyte, kidney epithelium
KCNT1	153	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CHD2	268	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
PRICKLE2	233	ubiquitous	marker	oviduct epithelium, cauda epididymis, colonic epithelium
CSTB	300	ubiquitous	marker	lower esophagus mucosa, tongue squamous epithelium, pharyngeal mucosa
RBFOX3	177	broad	marker	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere
SZT2	238	ubiquitous	marker	colonic epithelium, sural nerve, granulocyte
TBC1D24	227	ubiquitous	marker	parotid gland, Brodmann (1909) area 23, middle temporal gyrus
STRADA	162	ubiquitous	marker	right uterine tube, mucosa of stomach, left testis
EPM2A	281	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, hindlimb stylopod muscle
GRIN1	215	tissue_specific	marker	right hemisphere of cerebellum, right frontal lobe, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 33.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WWOX	5,892
SLC2A1	5,711
SCARB2	5,405
RBFOX3	4,442
MAF	4,111
GRIN2A	3,146
SPTAN1	3,083
RBFOX1	2,990
SLC6A1	2,841
SCN2A	2,810

Intra-cohort edges

A	B	Sources
CSTB	KCNQ3	string_interaction
CSTB	PRICKLE1	string_interaction
DEPDC5	KCNT1	string_interaction
DEPDC5	SZT2	biogrid_interaction, intact, string_interaction
GABRG2	PCDH19	string_interaction
GABRG2	SCN1A	string_interaction
GABRG2	SCN1B	string_interaction
GABRG2	SCN2A	string_interaction
GABRG2	SCN9A	string_interaction
GABRG2	SLC6A1	string_interaction
GRIN1	GRIN2A	biogrid_interaction
KCNQ3	KCNT1	string_interaction
KCNQ3	SCN1A	string_interaction
KCNQ3	SCN2A	string_interaction
KCNT1	PCDH19	string_interaction
KCNT1	SCN1A	string_interaction
KCNT1	SCN2A	string_interaction
KCNT1	TBC1D24	string_interaction
PCDH19	PLCB1	string_interaction
PCDH19	SCN1A	string_interaction
PCDH19	SCN1B	string_interaction
PCDH19	SCN2A	string_interaction
PCDH19	SPTAN1	intact, string_interaction
PCDH19	TBC1D24	string_interaction
RBFOX1	RBFOX3	biogrid_interaction
RELN	STRADA	string_interaction
SCN1A	SCN1B	biogrid_interaction, string_interaction
SCN1A	SCN2A	biogrid_interaction, string_interaction
SCN1A	TBC1D24	string_interaction
SCN1B	SCN2A	string_interaction
SCN1B	SCN9A	string_interaction
SCN2A	SCN9A	intact
SCN2A	TBC1D24	string_interaction

Structural data

PDB: 24 · AlphaFold-only: 10 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRIN1	Q05586	85
GABRG2	P18507	75
SCN9A	Q15858	43
SCN1B	Q07699	39
GRIN2A	Q12879	37
KCNQ3	O43525	16
DEPDC5	O75140	11
SCARB2	Q14108	10
SZT2	Q5T011	9
SPTAN1	Q13813	7
KCNT1	Q5JUK3	6
SCN2A	Q99250	5
SLC2A1	P11166	5
SLC6A1	P30531	5
RBFOX1	Q9NWB1	4
STRADA	Q7RTN6	4
CSTB	P04080	3
EPM2A	B3EWF7	2
ASAH1	Q13510	2
SCN1A	P35498	1
WWOX	Q9NZC7	1
CNTNAP2	Q9UHC6	1
PCDH19	Q8TAB3	1
RELN	P78509	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPA6	Q8N4T0	90.93
PLCB1	Q9NQ66	84.55
TBC1D24	Q9ULP9	84.46
BRWD3	Q6RI45	65.11
RBFOX3	A6NFN3	62.27
MAF	O75444	62.21
IER3IP1	Q9Y5U9	61.57
CHD2	O14647	60.81
PRICKLE2	Q7Z3G6	56.41
PRICKLE1	Q96MT3	55.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 113. Enrichment computed across 36 evidence-associated genes (28 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 28 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	6	78.9×	1e-08	SCN1A, SCN1B, SCN2A, SCN9A, SPTAN1, KCNQ3
L1CAM interactions	6	25.8×	5e-06	SCN1A, SCN1B, SCN2A, SCN9A, SPTAN1, KCNQ3
Phase 0 - rapid depolarisation	4	49.4×	4e-05	SCN1A, SCN1B, SCN2A, SCN9A
Axon guidance	6	9.7×	8e-04	SCN1A, SCN1B, SCN2A, SCN9A, SPTAN1, KCNQ3
Nervous system development	6	9.2×	8e-04	SCN1A, SCN1B, SCN2A, SCN9A, SPTAN1, KCNQ3
Sensory perception of taste	3	36.0×	0.001	SCN1B, SCN2A, SCN9A
Sensory perception of sweet, bitter, and umami (glutamate) taste	3	29.8×	0.002	SCN1B, SCN2A, SCN9A
Cardiac conduction	4	15.5×	0.002	SCN1A, SCN1B, SCN2A, SCN9A
Sensory Perception	4	13.6×	0.002	SCN1B, SCN2A, SCN9A, SPTAN1
Muscle contraction	4	11.0×	0.005	SCN1A, SCN1B, SCN2A, SCN9A
Unblocking of NMDA receptors, glutamate binding and activation	2	38.8×	0.010	GRIN2A, GRIN1
Synaptic adhesion-like molecules	2	38.8×	0.010	GRIN2A, GRIN1
Negative regulation of NMDA receptor-mediated neuronal transmission	2	38.8×	0.010	GRIN2A, GRIN1
Long-term potentiation	2	34.0×	0.012	GRIN2A, GRIN1
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)	1	407.9×	0.017	SLC2A1
Developmental Biology	7	3.6×	0.017	SCN1A, SCN1B, SCN2A, SCN9A, SPTAN1, KCNQ3, ASAH1
Assembly and cell surface presentation of NMDA receptors	2	18.1×	0.036	GRIN2A, GRIN1
Lactose synthesis	1	135.9×	0.046	SLC2A1
Amino acids regulate mTORC1	2	14.3×	0.050	DEPDC5, SZT2
Neurexins and neuroligins	2	14.1×	0.050	GRIN2A, GRIN1
Reuptake of GABA	1	102.0×	0.053	SLC6A1
MECP2 regulates transcription factors	1	81.6×	0.063	RBFOX1
Reelin signalling pathway	1	68.0×	0.072	RELN
Vitamin C (ascorbate) metabolism	1	51.0×	0.088	SLC2A1
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	51.0×	0.088	PLCB1
Myoclonic epilepsy of Lafora	1	45.3×	0.095	EPM2A
Acetylcholine regulates insulin secretion	1	40.8×	0.098	PLCB1
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	40.8×	0.098	WWOX
Caspase-mediated cleavage of cytoskeletal proteins	1	34.0×	0.109	SPTAN1
Activation of the TFAP2 (AP-2) family of transcription factors	1	34.0×	0.109	WWOX

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 34 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 transmembrane transport	7	41.8×	1e-07	GRIN2A, SCN1A, SCN1B, SCN2A, SCN9A, SLC6A1, GRIN1
cardiac muscle cell action potential involved in contraction	4	82.6×	3e-05	SCN1A, SCN1B, SCN2A, SCN9A
positive regulation of excitatory postsynaptic potential	4	62.0×	6e-05	GRIN2A, TBC1D24, GRIN1, RELN
neuronal action potential	4	56.6×	7e-05	SCN1A, SCN2A, SCN9A, KCNQ3
excitatory chemical synaptic transmission	3	114.4×	2e-04	GRIN2A, GRIN1, KCNQ3
positive regulation of synaptic transmission, glutamatergic	3	55.1×	0.001	GRIN2A, GRIN1, RELN
memory	4	21.6×	0.002	GRIN2A, SCN2A, SLC6A1, PLCB1
brain development	5	11.7×	0.003	GRIN2A, CNTNAP2, IER3IP1, GRIN1, RELN
dendrite development	3	34.6×	0.004	PRICKLE1, TBC1D24, RELN
regulation of monoatomic cation transmembrane transport	2	123.9×	0.004	GRIN2A, GRIN1
membrane depolarization during action potential	2	99.1×	0.006	SCN1A, SCN1B
calcium ion transmembrane import into cytosol	2	90.1×	0.007	GRIN2A, GRIN1
neuronal action potential propagation	2	82.6×	0.007	SCN1A, SCN1B
ionotropic glutamate receptor signaling pathway	2	76.2×	0.008	GRIN2A, GRIN1
regulation of synaptic plasticity	3	22.9×	0.008	GRIN2A, GRIN1, KCNQ3
glutamate receptor signaling pathway	2	55.1×	0.012	GRIN2A, PLCB1
nerve development	2	55.1×	0.012	SCN1A, KCNQ3
post-embryonic development	3	18.1×	0.012	GABRG2, SCN9A, SZT2
cerebral cortex development	3	18.1×	0.012	SLC2A1, CNTNAP2, PLCB1
gene expression	4	9.4×	0.016	PRICKLE1, IER3IP1, CHD2, KCNQ3
chemical synaptic transmission	4	9.1×	0.017	GRIN2A, SLC6A1, GRIN1, KCNQ3
regulation of neuronal synaptic plasticity	2	39.6×	0.020	GRIN2A, GRIN1
propylene metabolic process	1	495.6×	0.020	GRIN1
spinal cord patterning	1	495.6×	0.020	RELN
corticospinal neuron axon guidance	1	495.6×	0.020	SCN1B
regulation of carbohydrate catabolic process	1	495.6×	0.020	SCARB2
regulation of programmed necrotic cell death	1	495.6×	0.020	ASAH1
apoptosome assembly	1	495.6×	0.020	KCNQ3
action potential propagation	1	495.6×	0.020	SCN9A
regulation of action potential firing threshold	1	495.6×	0.020	KCNQ3

Therapeutics

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 11 · Phased (≥1): 14 · Undrugged: 22

Druggability breadth: 18 of 36 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
GABRG2	ENZALUTAMIDE
GRIN2A	MEMANTINE HYDROCHLORIDE
SCN1A	MEXILETINE HYDROCHLORIDE
SCN2A	BEPRIDIL
SCN9A	IMIPRAMINE
SLC2A1	EMETINE
SLC6A1	TIAGABINE
KCNT1	BEPRIDIL
STRADA	RUXOLITINIB
GRIN1	DEXTROMETHORPHAN
KCNQ3	FLUPIRTINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
SCN1A	94	4
GABRG2	55	4
GRIN1	39	4
GRIN2A	37	4
SCN9A	36	4
SLC2A1	7	4
STRADA	5	4
SLC6A1	3	4
KCNQ3	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENZALUTAMIDE	4	GABRG2
DIAZEPAM	4	GABRG2
LIOTHYRONINE	4	GABRG2
GANAXOLONE	4	GABRG2
BREXANOLONE	4	GABRG2
APALUTAMIDE	4	GABRG2
FLUMAZENIL	4	GABRG2
CLONAZEPAM	4	GABRG2
FLUNITRAZEPAM	4	GABRG2
CHLORDIAZEPOXIDE	4	GABRG2
TRIAZOLAM	4	GABRG2
ZOLPIDEM	4	GABRG2
LINDANE	4	GABRG2
PROPOFOL	4	GABRG2
ZALEPLON	4	GABRG2
STIRIPENTOL	4	GABRG2
ZURANOLONE	4	GABRG2
ALPRAZOLAM	4	GABRG2
ETOMIDATE	4	GABRG2
ESZOPICLONE	4	GABRG2
PENTOBARBITAL	4	GABRG2
CANDESARTAN CILEXETIL	4	GABRG2
SIMVASTATIN	4	GABRG2
EPINASTINE	4	GABRG2
GLAFENINE	4	GABRG2
TIPRANAVIR	4	GABRG2
BENPERIDOL	4	GABRG2
ASENAPINE	4	GABRG2
TROGLITAZONE	4	GABRG2
CLOZAPINE	4	GABRG2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
GABRG2	1,155	Binding:940, Functional:201, ADMET:10, Toxicity:4
GRIN1	481	Binding:435, Functional:40, ADMET:5, Toxicity:1
SCN9A	428	Binding:395, Functional:29, ADMET:3, Toxicity:1
GRIN2A	324	Binding:296, Functional:23, ADMET:4, Toxicity:1
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
SLC2A1	158	Binding:130, ADMET:24, Functional:4
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
ASAH1	111	Binding:108, Functional:3
KCNQ3	97	Binding:91, Functional:4, ADMET:1, Toxicity:1
SLC6A1	56	Binding:55, Functional:1
STRADA	47	Binding:47
KCNT1	24	Binding:24
SCN1B	15	Binding:7, ADMET:6, Toxicity:2
PLCB1	11	Binding:9, Functional:2
SPTAN1	7	Binding:7
BRWD3	5	Binding:5
CSTB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLCB1	3.1.4.11	phosphoinositide phospholipase C
EPM2A	3.1.3.16	protein-serine/threonine phosphatase
ASAH1	3.5.1.23	ceramidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GABRG2	1,155
GRIN2A	324
SCN1A	149
SCN2A	203
SCN9A	428
SLC2A1	158
GRIN1	481
ASAH1	111

Pharmacogenomics

Cohort genes with a PharmGKB record: 33; 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)
ENZALUTAMIDE	4	GABRG2
DIAZEPAM	4	GABRG2
LIOTHYRONINE	4	GABRG2
GANAXOLONE	4	GABRG2
BREXANOLONE	4	GABRG2
APALUTAMIDE	4	GABRG2
FLUMAZENIL	4	GABRG2
CLONAZEPAM	4	GABRG2
FLUNITRAZEPAM	4	GABRG2
CHLORDIAZEPOXIDE	4	GABRG2
TRIAZOLAM	4	GABRG2
ZOLPIDEM	4	GABRG2
LINDANE	4	GABRG2
PROPOFOL	4	GABRG2
ZALEPLON	4	GABRG2
STIRIPENTOL	4	GABRG2
ZURANOLONE	4	GABRG2
ALPRAZOLAM	4	GABRG2
ETOMIDATE	4	GABRG2
ESZOPICLONE	4	GABRG2
PENTOBARBITAL	4	GABRG2
CANDESARTAN CILEXETIL	4	GABRG2
SIMVASTATIN	4	GABRG2
EPINASTINE	4	GABRG2
GLAFENINE	4	GABRG2
TIPRANAVIR	4	GABRG2
BENPERIDOL	4	GABRG2
ASENAPINE	4	GABRG2
TROGLITAZONE	4	GABRG2
CLOZAPINE	4	GABRG2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	GABRG2, GRIN2A, SCN1A, SCN2A, SCN9A, SLC2A1, SLC6A1, KCNT1, STRADA, GRIN1 (+1 more)
B	Phased (≥1) drug, not yet approved	3	SCN1B, SPTAN1, ASAH1
C	Druggable family + PDB, no drug	1	EPM2A
D	Druggable family + AlphaFold only, no drug	2	PLCB1, CPA6
E	Difficult family or no structure, no drug	19	BRWD3, WWOX, CNTNAP2, PCDH19, SCARB2, PRICKLE1, RBFOX1, DEPDC5, IER3IP1, CHD2 (+9 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PCDH19	0	SCN1A
TBC1D24	0	KCNT1
BRWD3	5	—
WWOX	0	—
CNTNAP2	0	—
PLCB1	11	—
SCARB2	0	—
PRICKLE1	0	—
CPA6	0	—
RBFOX1	0	—
DEPDC5	0	—
IER3IP1	0	—
CHD2	0	—
PRICKLE2	0	—
CSTB	1	—
RBFOX3	0	—
SZT2	0	—
EPM2A	0	—
SCN1A-AS1	0	—
ARFGEF1-DT	0	—
MAF	0	—
RELN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT03865771	Not specified	RECRUITING	Sleep Related Memory Consolidation in Children With Age Related Focal Epilepsy.
NCT06545708	Not specified	RECRUITING	Music Perception in SeLECTs
NCT01046760	Not specified	UNKNOWN	Scholar Performance and Praxis Assessment in Children With Rolandic Epilepsy
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT01515436	Not specified	COMPLETED	The Effect of Music Periodicity on Interictal Epileptiform Discharges
NCT03465566	Not specified	UNKNOWN	Emotion Recognition in Benign Epilepsy of Childhood With Centro-Temporal Spikes (BECTS)
NCT03547050	Not specified	COMPLETED	Rolandic Epilepsy Genomewide Association International Study
NCT04325282	Not specified	COMPLETED	Transcranial Magnetic Stimulation for BECTS
NCT04357236	Not specified	COMPLETED	18F-FDG PET Imaging Analysis of Antiepileptic Drug Response in BECTS
NCT04569708	Not specified	COMPLETED	Sleep Spindles and Memory in Rolandic Epilepsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBAMAZEPINE	4	1
LEVETIRACETAM	4	1
ETIRACETAM	2	1
LEVITIRACETAM	0	1