Myoclonic epilepsy

Summary

Myoclonic epilepsy (MONDO:0100577) is a disease (an umbrella term covering 7 Mondo subtypes) with 4 cohort genes and 1 clinical trial.

At a glance

• Umbrella term: 7 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 4
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonic epilepsy
Mondo ID	MONDO:0100577
UMLS	C0014550
MedGen	4988
GARD	0027276
Is cancer (heuristic)	no

Also known as: myoclonic epilepsy syndrome

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 7 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 › myoclonic epilepsy

Related subtypes (7): adolescence-adult electroclinical syndrome, benign focal seizures of adolescence, neonatal epilepsy syndrome, infantile epilepsy syndrome, childhood-onset epilepsy syndrome, neonatal/infantile epilepsy syndrome, variable age epilepsy syndrome

Subtypes (7): epilepsy, familial adult myoclonic, myoclonic epilepsy, Hartung type, juvenile myoclonic epilepsy, familial infantile myoclonic epilepsy, myoclonic epilepsy in non-progressive encephalopathies, progressive myoclonus epilepsy, myoclonic epilepsy in infancy

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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
204982	NM_000742.4(CHRNA2):c.202C>T (p.Arg68Trp)	CHRNA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1325551	NM_198859.4(PRICKLE2):c.1706G>A (p.Arg569Gln)	PRICKLE2	Uncertain significance	criteria provided, single submitter
1341805	NM_198859.4(PRICKLE2):c.2246C>T (p.Pro749Leu)	PRICKLE2-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
560660	NM_001165963.4(SCN1A):c.1889G>C (p.Arg630Pro)	SCN1A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
CHRNA2	Orphanet:98784	Sleep-related hypermotor epilepsy
PRICKLE2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
PRICKLE2	Orphanet:402082	Progressive myoclonic epilepsy type 5

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	clinvar
CHRNA2	HGNC:1956	ENSG00000120903	Q15822	Neuronal acetylcholine receptor subunit alpha-2	clinvar
PRICKLE2	HGNC:20340	ENSG00000163637	Q7Z3G6	Prickle-like protein 2	clinvar
PRICKLE2-AS1	HGNC:40916	ENSG00000241572		PRICKLE2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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…
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.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · 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	27.9×	0.106
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
CHRNA2	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
PRICKLE2	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
PRICKLE2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
primary visual cortex	1
cervix squamous epithelium	1
gingival epithelium	1
primordial germ cell in gonad	1
cauda epididymis	1
colonic epithelium	1
oviduct epithelium	1
ganglionic eminence	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
CHRNA2	143	tissue_specific	yes	cervix squamous epithelium, primordial germ cell in gonad, gingival epithelium
PRICKLE2	233	ubiquitous	marker	oviduct epithelium, cauda epididymis, colonic epithelium
PRICKLE2-AS1	86		yes	male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN1A	2,287
PRICKLE2	1,151
CHRNA2	982
PRICKLE2-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN1A	P35498	1
CHRNA2	Q15822	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRICKLE2	Q7Z3G6	56.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 4 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Highly calcium permeable nicotinic acetylcholine receptors	1	634.4×	0.008	CHRNA2
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	519.1×	0.008	CHRNA2
Presynaptic nicotinic acetylcholine receptors	1	475.8×	0.008	CHRNA2
Acetylcholine binding and downstream events	1	407.9×	0.008	CHRNA2
Postsynaptic nicotinic acetylcholine receptors	1	407.9×	0.008	CHRNA2
Interaction between L1 and Ankyrins	1	184.2×	0.013	SCN1A
Phase 0 - rapid depolarisation	1	173.0×	0.013	SCN1A
L1CAM interactions	1	60.1×	0.032	SCN1A
Cardiac conduction	1	54.4×	0.032	SCN1A
Neurotransmitter receptors and postsynaptic signal transmission	1	50.1×	0.032	CHRNA2
Muscle contraction	1	38.6×	0.035	SCN1A
Transmission across Chemical Synapses	1	38.1×	0.035	CHRNA2
Axon guidance	1	22.6×	0.049	SCN1A
Neuronal System	1	22.1×	0.049	CHRNA2
Nervous system development	1	21.5×	0.049	SCN1A
Developmental Biology	1	7.2×	0.134	SCN1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
modulation of inhibitory postsynaptic potential	1	5617.3×	0.005	CHRNA2
protein localization to axon	1	1123.5×	0.010	PRICKLE2
cellular response to nicotine	1	702.2×	0.010	CHRNA2
membrane depolarization during action potential	1	561.7×	0.010	SCN1A
neuronal action potential propagation	1	468.1×	0.010	SCN1A
detection of mechanical stimulus involved in sensory perception of pain	1	374.5×	0.010	SCN1A
neuromuscular process controlling posture	1	351.1×	0.010	SCN1A
nerve development	1	312.1×	0.010	SCN1A
synaptic transmission, cholinergic	1	267.5×	0.010	CHRNA2
blastocyst formation	1	255.3×	0.010	PRICKLE2
cardiac muscle cell action potential involved in contraction	1	234.1×	0.010	SCN1A
acetylcholine receptor signaling pathway	1	208.1×	0.010	CHRNA2
neuromuscular synaptic transmission	1	200.6×	0.010	CHRNA2
membrane depolarization	1	170.2×	0.010	CHRNA2
adult walking behavior	1	165.2×	0.010	SCN1A
neuronal action potential	1	160.5×	0.010	SCN1A
Wnt signaling pathway, planar cell polarity pathway	1	151.8×	0.010	PRICKLE2
presynaptic modulation of chemical synaptic transmission	1	151.8×	0.010	CHRNA2
determination of adult lifespan	1	144.0×	0.010	SCN1A
response to nicotine	1	140.4×	0.010	CHRNA2
sodium ion transport	1	90.6×	0.014	SCN1A
regulation of synaptic plasticity	1	86.4×	0.014	CHRNA2
monoatomic ion transmembrane transport	1	69.3×	0.017	CHRNA2
sodium ion transmembrane transport	1	67.7×	0.017	SCN1A
establishment of localization in cell	1	53.5×	0.020	SCN1A
monoatomic ion transport	1	52.0×	0.020	CHRNA2
signal transduction	1	5.3×	0.176	CHRNA2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 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
SCN1A	MEXILETINE HYDROCHLORIDE
CHRNA2	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
CHRNA2	4	4
PRICKLE2	0	0
PRICKLE2-AS1	0	0

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
CHRNA2	40	Binding:37, Functional:2, ADMET:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SCN1A	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	SCN1A, CHRNA2
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	2	PRICKLE2, PRICKLE2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRICKLE2	0	—
PRICKLE2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00006191	Not specified	COMPLETED	Effect of Levetiracetam on Brain Excitability