Juvenile myoclonic epilepsy

Summary

Juvenile myoclonic epilepsy (MONDO:0009696) is a disease with 8 cohort genes (4 GWAS associations across 2 studies) and 2 clinical trials. Top therapeutic interventions include flunarizine hydrochloride.

At a glance

• Prevalence: 1-9 / 100 000 (Norway) [Orphanet-validated]
• Cohort genes: 8
• GWAS associations: 4
• ClinVar variants: 29
• Phenotypes (HPO): 11
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.7	Norway	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0002197	Generalized-onset seizure	Very frequent (80-99%)
HP:0002392	EEG with polyspike wave complexes	Very frequent (80-99%)
HP:0007000	Morning myoclonic jerks	Very frequent (80-99%)
HP:0000153	Abnormality of the mouth	Frequent (30-79%)
HP:0000496	Abnormality of eye movement	Frequent (30-79%)
HP:0002121	Generalized non-motor (absence) seizure	Occasional (5-29%)
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)	Occasional (5-29%)
HP:0007207	Photosensitive tonic-clonic seizures	Occasional (5-29%)
HP:0001249	Intellectual disability	Excluded (0%)
HP:0000718	Aggressive behavior	Very rare (<1-4%)
HP:0002133	Status epilepticus	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile myoclonic epilepsy
Mondo ID	MONDO:0009696
MeSH	D020190
OMIM	254770, 606904
Orphanet	307
DOID	DOID:4890
ICD-10-CM	G40.B
ICD-11	1014397110
NCIT	C84796
SNOMED CT	6204001
UMLS	C0270853
MedGen	78738
GARD	0006808
MedDRA	10071082
Is cancer (heuristic)	no

Also known as: EJM · epilepsy, myoclonic juvenile · JME · juvenile myoclonus epilepsy · myoclonic epilepsy, juvenile · myoclonic epilepsy, juvenile, 1 · myoclonic epilepsy, juvenile, susceptibility to, 1 · petit mal, impulsive

Data availability: 29 ClinVar variants · 4 GWAS associations (2 studies) · 4 GenCC gene-disease records · 10 cell lines.

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 › epilepsy syndrome › myoclonic epilepsy › juvenile myoclonic epilepsy

Related subtypes (6): epilepsy, familial adult myoclonic, myoclonic epilepsy, Hartung type, familial infantile myoclonic epilepsy, myoclonic epilepsy in non-progressive encephalopathies, progressive myoclonus epilepsy, myoclonic epilepsy in infancy

Subtypes (1): myoclonic epilepsy, juvenile, 2

Genetics & variants

GWAS landscape

4 GWAS associations across 2 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1046276	3e-11	CTF1	T	6.67
rs3019359	3e-08	TMEM74	T
rs17537141	5e-08	GABRA2	T

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90271614	International League Against Epilepsy Consortium on Complex Epilepsies	2023	1,732	42,436	GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture.
GCST007347	International League Against Epilepsy Consortium on Complex Epilepsies	2018	1,177	4,218	Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
3_prime_UTR_variant	1
intergenic_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1046276	16	30903305	T>A,C,G	0.34	3_prime_UTR_variant	CTF1	3e-11	Tier 2: splice/UTR
rs3019359	8	108742712	T>A,C,G	0.05	intergenic_variant	TMEM74	3e-08	Tier 4: intronic/intergenic
rs17537141	4	46300407	T>C	0.05	intron_variant	GABRA2	5e-08	Tier 4: intronic/intergenic

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 6 conflicting classifications of pathogenicity, 5 benign/likely benign, 2 likely pathogenic, 1 benign, 1 not provided, 1 pathogenic, 1 association

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580936	NM_005898.5(CAPRIN1):c.891_894del (p.Arg297fs)	CAPRIN1	Pathogenic	criteria provided, single submitter
802172	NM_001127644.2(GABRA1):c.268G>A (p.Asp90Asn)	GABRA1	Likely pathogenic	criteria provided, single submitter
802173	NM_001127644.2(GABRA1):c.897T>G (p.Ser299Arg)	GABRA1	Likely pathogenic	criteria provided, single submitter
7608	NM_000726.5(CACNB4):c.311G>T (p.Cys104Phe)	CACNB4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
332448	NM_000079.4(CHRNA1):c.319C>T (p.Arg107Cys)	CHRNA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128963	NM_018100.4(EFHC1):c.1385T>C (p.Ile462Thr)	EFHC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205398	NM_018100.4(EFHC1):c.151C>T (p.Arg51Trp)	EFHC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205403	NM_018100.4(EFHC1):c.1114C>T (p.Arg372Trp)	EFHC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205414	NM_018100.4(EFHC1):c.1612C>T (p.Arg538Ter)	EFHC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451830	NM_018896.5(CACNA1G):c.3315C>A (p.Ser1105Arg)	CACNA1G	Uncertain significance	criteria provided, single submitter
205391	NM_018100.4(EFHC1):c.817G>T (p.Val273Leu)	EFHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
205393	NM_018100.4(EFHC1):c.911A>G (p.Asn304Ser)	EFHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
205417	NM_018100.4(EFHC1):c.1892A>G (p.Tyr631Cys)	EFHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
572744	NM_018100.4(EFHC1):c.880C>T (p.Arg294Cys)	EFHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
580362	NM_018100.4(EFHC1):c.165C>G (p.Asn55Lys)	EFHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
646256	NM_018100.4(EFHC1):c.598G>C (p.Glu200Gln)	EFHC1	Uncertain significance	criteria provided, single submitter
830042	NM_018100.4(EFHC1):c.723+18_723+19insG	EFHC1	association	no assertion criteria provided
830045	NM_018100.4(EFHC1):c.1365T>C (p.Pro455=)	EFHC1	Uncertain significance	no assertion criteria provided
832614	NC_000006.12:g.(?52423789)(52492432_?)del	EFHC1	Uncertain significance	criteria provided, single submitter
833385	NC_000006.12:g.(?52479017)(52492432_?)del	EFHC1	Uncertain significance	criteria provided, single submitter
848884	NM_018100.4(EFHC1):c.1286C>T (p.Pro429Leu)	EFHC1	Uncertain significance	criteria provided, single submitter
2011538	NM_001127644.2(GABRA1):c.35G>T (p.Trp12Leu)	GABRA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
128966	NM_018100.4(EFHC1):c.1855A>C (p.Ile619Leu)	EFHC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128967	NM_018100.4(EFHC1):c.25T>C (p.Leu9=)	EFHC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128968	NM_018100.4(EFHC1):c.475C>T (p.Arg159Trp)	EFHC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128969	NM_018100.4(EFHC1):c.573+10A>G	EFHC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128970	NM_018100.4(EFHC1):c.881G>A (p.Arg294His)	EFHC1	Benign	criteria provided, multiple submitters, no conflicts
2063	NM_018100.4(EFHC1):c.545G>A (p.Arg182His)	EFHC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1810305	NM_018896.5(CACNA1G):c.6508T>A (p.Trp2170Arg)	CACNA1G	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
STX1B	STX1B	GWAS, Orphanet

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
GABRA1	Strong	Autosomal dominant	epilepsy, idiopathic generalized, susceptibility to, 13	7
CACNB4	Supportive	Autosomal dominant	juvenile myoclonic epilepsy	4
CILK1	Supportive	Autosomal dominant	juvenile myoclonic epilepsy	5
EFHC1	Limited	Autosomal dominant	juvenile myoclonic epilepsy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CACNB4	Orphanet:211067	Episodic ataxia type 5
CACNB4	Orphanet:307	Juvenile myoclonic epilepsy
EFHC1	Orphanet:1941	Juvenile absence epilepsy
EFHC1	Orphanet:307	Juvenile myoclonic epilepsy
GABRA1	Orphanet:307	Juvenile myoclonic epilepsy
GABRA1	Orphanet:33069	Dravet syndrome
GABRA1	Orphanet:64280	Childhood absence epilepsy
CILK1	Orphanet:199332	Endocrine-cerebro-osteodysplasia syndrome
CILK1	Orphanet:307	Juvenile myoclonic epilepsy
CACNA1G	Orphanet:458803	Spinocerebellar ataxia type 42
STX1B	Orphanet:36387	Genetic epilepsy with febrile seizure plus
CHRNA1	Orphanet:33108	Lethal multiple pterygium syndrome
CHRNA1	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
CAPRIN1	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CACNB4	HGNC:1404	ENSG00000182389	O00305	Voltage-dependent L-type calcium channel subunit beta-4	gencc,clinvar
EFHC1	HGNC:16406	ENSG00000096093	Q5JVL4	EF-hand domain-containing protein 1	gencc,clinvar
GABRA1	HGNC:4075	ENSG00000022355	P14867	Gamma-aminobutyric acid receptor subunit alpha-1	gencc,clinvar
CILK1	HGNC:21219	ENSG00000112144	Q9UPZ9	Serine/threonine-protein kinase ICK	gencc
CACNA1G	HGNC:1394	ENSG00000006283	O43497	Voltage-dependent T-type calcium channel subunit alpha-1G	clinvar
STX1B	HGNC:18539	ENSG00000099365	P61266	Syntaxin-1B	gwas
CHRNA1	HGNC:1955	ENSG00000138435	P02708	Acetylcholine receptor subunit alpha	clinvar
CAPRIN1	HGNC:6743	ENSG00000135387	Q14444	Caprin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CACNB4	Voltage-dependent L-type calcium channel subunit beta-4	The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition…
EFHC1	EF-hand domain-containing protein 1	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
GABRA1	Gamma-aminobutyric acid receptor subunit alpha-1	Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
CILK1	Serine/threonine-protein kinase ICK	Required for ciliogenesis.
CACNA1G	Voltage-dependent T-type calcium channel subunit alpha-1G	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
STX1B	Syntaxin-1B	Potentially involved in docking of synaptic vesicles at presynaptic active zones.
CHRNA1	Acetylcholine receptor subunit alpha	Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
CAPRIN1	Caprin-1	mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in neurogenesis, synaptic plasticity in neurons and cell proliferation and migration in multiple cell types.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 5 · Druggable fraction: 0.25

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	1	13.9×	0.278
Kinase	1	3.5×	0.496
Scaffold/PPI	1	2.2×	0.496
Other/Unknown	5	1.1×	0.496

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CACNB4	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, GK/Ca_channel_bsu
EFHC1	Other/Unknown	no		EF_hand_dom, DM10_dom, EF-hand-dom_pair
GABRA1	Other/Unknown	no		GABAAa_rcpt, GABBAa1_rcpt, GABAA/Glycine_rcpt
CILK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CACNA1G	Ion channel	yes		VDCCAlpha1, VDCC_T_a1, Ion_trans_dom
STX1B	Other/Unknown	no		T_SNARE_dom, Syntaxin_N, Syntaxin/epimorphin_CS
CHRNA1	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CAPRIN1	Other/Unknown	no		Caprin-1_C, Caprin, Caprin-1_dimer

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
lateral nuclear group of thalamus	3
cortical plate	2
right hemisphere of cerebellum	2
cerebellar vermis	1
primary visual cortex	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1
endothelial cell	1
middle temporal gyrus	1
adrenal tissue	1
palpebral conjunctiva	1
right frontal lobe	1
cerebellar cortex	1
cerebellar hemisphere	1
gastrocnemius	1
gluteal muscle	1
muscle of leg	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CACNB4	201	broad	marker	cerebellar vermis, lateral nuclear group of thalamus, primary visual cortex
EFHC1	272	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
GABRA1	130	tissue_specific	marker	lateral nuclear group of thalamus, endothelial cell, middle temporal gyrus
CILK1	268	ubiquitous	marker	adrenal tissue, palpebral conjunctiva, cortical plate
CACNA1G	194	broad	yes	lateral nuclear group of thalamus, right hemisphere of cerebellum, right frontal lobe
STX1B	176	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CHRNA1	149	broad	marker	gastrocnemius, gluteal muscle, muscle of leg
CAPRIN1	294	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAPRIN1	2,650
EFHC1	2,470
GABRA1	2,469
STX1B	2,130
CACNA1G	1,677
CACNB4	1,366
CILK1	1,317
CHRNA1	1,058

Intra-cohort edges

A	B	Sources
CACNB4	EFHC1	string_interaction
CACNB4	GABRA1	string_interaction
CILK1	EFHC1	string_interaction
EFHC1	GABRA1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GABRA1	P14867	86
CHRNA1	P02708	15
CAPRIN1	Q14444	6
EFHC1	Q5JVL4	2
CACNA1G	O43497	2
CACNB4	O00305	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STX1B	P61266	84.17
CILK1	Q9UPZ9	61.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 8 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
NCAM signaling for neurite out-growth	2	108.8×	0.002	CACNB4, CACNA1G
NCAM1 interactions	2	99.3×	0.002	CACNB4, CACNA1G
Toxicity of botulinum toxin type C (botC)	1	761.3×	0.009	STX1B
Neurotoxicity of clostridium toxins	1	285.5×	0.009	STX1B
Highly calcium permeable nicotinic acetylcholine receptors	1	253.8×	0.009	CHRNA1
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	207.6×	0.009	CHRNA1
Presynaptic depolarization and calcium channel opening	1	190.3×	0.009	CACNB4
Presynaptic nicotinic acetylcholine receptors	1	190.3×	0.009	CHRNA1
Acetylcholine binding and downstream events	1	163.1×	0.009	CHRNA1
Uptake and actions of bacterial toxins	1	163.1×	0.009	STX1B
LGI-ADAM interactions	1	163.1×	0.009	STX1B
Postsynaptic nicotinic acetylcholine receptors	1	163.1×	0.009	CHRNA1
Transmission across Chemical Synapses	2	30.4×	0.009	CACNB4, CHRNA1
Axon guidance	2	18.1×	0.009	CACNB4, CACNA1G
Neuronal System	2	17.7×	0.009	CACNB4, CHRNA1
Nervous system development	2	17.2×	0.009	CACNB4, CACNA1G
Developmental Biology	3	8.7×	0.009	CACNB4, CACNA1G, STX1B
Bacterial Infection Pathways	1	67.2×	0.021	STX1B
GABA receptor activation	1	63.4×	0.021	GABRA1
Signaling by ERBB4	1	54.4×	0.022	GABRA1
Smooth Muscle Contraction	1	53.1×	0.022	CACNA1G
Neurotransmitter receptors and postsynaptic signal transmission	1	20.0×	0.056	CHRNA1
Muscle contraction	1	15.4×	0.069	CACNA1G
Infectious disease	1	5.0×	0.194	STX1B
Disease	1	2.6×	0.328	STX1B

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
gamma-aminobutyric acid signaling pathway	2	135.9×	0.004	CACNB4, GABRA1
neuromuscular junction development	2	131.7×	0.004	CACNB4, CHRNA1
SA node cell to atrial cardiac muscle cell signaling	1	2106.5×	0.005	CACNA1G
AV node cell to bundle of His cell signaling	1	2106.5×	0.005	CACNA1G
regulation of deadenylation-dependent decapping of nuclear-transcribed mRNA	1	2106.5×	0.005	CAPRIN1
negative regulation of synaptic vesicle recycling	1	2106.5×	0.005	STX1B
positive regulation of spontaneous neurotransmitter secretion	1	2106.5×	0.005	STX1B
negative regulation of macropinocytosis	1	2106.5×	0.005	STX1B
regulation of membrane potential	2	57.7×	0.005	CACNA1G, CHRNA1
calcium ion transmembrane transport	2	52.7×	0.006	CACNB4, CACNA1G
response to nickel cation	1	1053.2×	0.008	CACNA1G
gamma-aminobutyric acid secretion	1	526.6×	0.011	CACNB4
cAMP metabolic process	1	526.6×	0.011	CACNB4
calcium ion-regulated exocytosis of neurotransmitter	1	526.6×	0.011	STX1B
regulation of synaptic activity	1	526.6×	0.011	STX1B
AV node cell action potential	1	526.6×	0.011	CACNA1G
positive regulation of stress granule assembly	1	421.3×	0.011	CAPRIN1
membrane depolarization during AV node cell action potential	1	421.3×	0.011	CACNA1G
membrane depolarization during SA node cell action potential	1	421.3×	0.011	CACNA1G
skeletal muscle tissue growth	1	351.1×	0.011	CHRNA1
musculoskeletal movement	1	351.1×	0.011	CHRNA1
spontaneous neurotransmitter secretion	1	351.1×	0.011	STX1B
SA node cell action potential	1	351.1×	0.011	CACNA1G
positive regulation of protein localization to nucleolus	1	351.1×	0.011	CACNB4
sinoatrial node development	1	263.3×	0.013	CACNA1G
intracellular mRNA localization	1	263.3×	0.013	CAPRIN1
Peyer’s patch development	1	263.3×	0.013	CACNB4
positive regulation of neurotransmitter secretion	1	234.1×	0.013	STX1B
regulation of atrial cardiac muscle cell membrane depolarization	1	234.1×	0.013	CACNA1G
chemical synaptic transmission	2	19.3×	0.013	CACNB4, CACNA1G

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Stiripentol	Approved (phase 4)

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
CACNB4	NIMODIPINE
GABRA1	DIAZEPAM
CILK1	MOMELOTINIB
CACNA1G	NIMODIPINE
CHRNA1	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GABRA1	60	4
CILK1	24	4
CHRNA1	12	4
CACNA1G	8	4
CACNB4	2	4
EFHC1	0	0
STX1B	0	0
CAPRIN1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNA1G, CACNB4
TACRINE	4	CACNA1G, CACNB4
DIAZEPAM	4	GABRA1
FLUNITRAZEPAM	4	GABRA1
ESZOPICLONE	4	GABRA1
FLUMAZENIL	4	GABRA1
TRIAZOLAM	4	GABRA1
ALPRAZOLAM	4	GABRA1
ETOMIDATE	4	GABRA1
ZOLPIDEM	4	GABRA1
ENZALUTAMIDE	4	GABRA1
LIOTHYRONINE	4	GABRA1
GANAXOLONE	4	GABRA1
BREXANOLONE	4	GABRA1
APALUTAMIDE	4	GABRA1
CLONAZEPAM	4	GABRA1
LINDANE	4	GABRA1
CHLORDIAZEPOXIDE	4	GABRA1
PROPOFOL	4	GABRA1
ZALEPLON	4	GABRA1
STIRIPENTOL	4	GABRA1
ZURANOLONE	4	GABRA1
CANDESARTAN CILEXETIL	4	GABRA1
SIMVASTATIN	4	GABRA1
EPINASTINE	4	GABRA1
GLAFENINE	4	GABRA1
TIPRANAVIR	4	GABRA1
BENPERIDOL	4	GABRA1
ASENAPINE	4	GABRA1
TROGLITAZONE	4	GABRA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GABRA1	842	Binding:701, Functional:124, ADMET:13, Toxicity:4
CHRNA1	157	Binding:107, Functional:47, ADMET:2, Toxicity:1
CILK1	119	Binding:119
CACNA1G	105	Binding:91, Functional:11, ADMET:2, Toxicity:1
CACNB4	13	Binding:13
CAPRIN1	2	Binding:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GABRA1	842
CILK1	119
CACNA1G	105
CHRNA1	157

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)
NIMODIPINE	4	CACNA1G, CACNB4
TACRINE	4	CACNA1G, CACNB4
DIAZEPAM	4	GABRA1
FLUNITRAZEPAM	4	GABRA1
ESZOPICLONE	4	GABRA1
FLUMAZENIL	4	GABRA1
TRIAZOLAM	4	GABRA1
ALPRAZOLAM	4	GABRA1
ETOMIDATE	4	GABRA1
ZOLPIDEM	4	GABRA1
ENZALUTAMIDE	4	GABRA1
LIOTHYRONINE	4	GABRA1
GANAXOLONE	4	GABRA1
BREXANOLONE	4	GABRA1
APALUTAMIDE	4	GABRA1
CLONAZEPAM	4	GABRA1
LINDANE	4	GABRA1
CHLORDIAZEPOXIDE	4	GABRA1
PROPOFOL	4	GABRA1
ZALEPLON	4	GABRA1
STIRIPENTOL	4	GABRA1
ZURANOLONE	4	GABRA1
CANDESARTAN CILEXETIL	4	GABRA1
SIMVASTATIN	4	GABRA1
EPINASTINE	4	GABRA1
GLAFENINE	4	GABRA1
TIPRANAVIR	4	GABRA1
BENPERIDOL	4	GABRA1
ASENAPINE	4	GABRA1
TROGLITAZONE	4	GABRA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	CACNB4, GABRA1, CILK1, CACNA1G, CHRNA1
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	EFHC1, STX1B, CAPRIN1

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)
EFHC1	0	CACNB4
STX1B	0	—
CAPRIN1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06153186	PHASE2	TERMINATED	Flunarizine for Treatment Resistant Absence Epilepsy
NCT03400371	Not specified	RECRUITING	Biology of Juvenile Myoclonic Epilepsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUNARIZINE HYDROCHLORIDE	2	1