Benign adult familial myoclonic epilepsy

Summary

Benign adult familial myoclonic epilepsy (MONDO:0019448) is a disease with 6 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Japan) [Orphanet-validated]
• Cohort genes: 6
• ClinVar variants: 1
• Phenotypes (HPO): 8

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2.8	Japan	Validated

Signs & symptoms

Clinical features (HPO)

8 HPO clinical features (Orphanet curated; top 8 by frequency):

HPO ID	Term	Frequency
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0002353	EEG abnormality	Very frequent (80-99%)
HP:0002378	Hand tremor	Very frequent (80-99%)
HP:0002197	Generalized-onset seizure	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0100576	Amaurosis fugax	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	benign adult familial myoclonic epilepsy
Mondo ID	MONDO:0019448
Orphanet	86814
ICD-11	1036649329
SNOMED CT	717225001
UMLS	C4273988
MedGen	908684
GARD	0016758
Is cancer (heuristic)	no

Also known as: ADCME · autosomal dominant cortical myoclonus and epilepsy · BAFME · benign adult familial myoclonus epilepsy · FAME · familial adult myoclonic epilepsy · familial cortical myoclonic tremor and epilepsy · FCMTE

Data availability: 1 ClinVar variant · 6 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › epilepsy, familial adult myoclonic › benign adult familial myoclonic epilepsy

Related subtypes (7): epilepsy, familial adult myoclonic, 1, epilepsy, familial adult myoclonic, 2, epilepsy, familial adult myoclonic, 3, epilepsy, familial adult myoclonic, 4, epilepsy, familial adult myoclonic, 5, epilepsy, familial adult myoclonic, 6, epilepsy, familial adult myoclonic, 7

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3780809	NM_018023.5(YEATS2):c.571del (p.Glu191fs)	YEATS2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 8 · 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
CNTN2	Strong	Autosomal recessive	epilepsy, familial adult myoclonic, 5	3
SAMD12	Strong	Autosomal dominant	epilepsy, familial adult myoclonic, 1	3
ADRA2B	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy	4
CTNND2	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy	3
MARCHF6	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy
YEATS2	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YEATS2	Orphanet:86814	Familial adult myoclonic epilepsy
CNTN2	Orphanet:86814	Familial adult myoclonic epilepsy
CTNND2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CTNND2	Orphanet:281	Monosomy 5p syndrome
CTNND2	Orphanet:86814	Familial adult myoclonic epilepsy
ADRA2B	Orphanet:86814	Familial adult myoclonic epilepsy
MARCHF6	Orphanet:86814	Familial adult myoclonic epilepsy
SAMD12	Orphanet:86814	Familial adult myoclonic epilepsy

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
YEATS2	HGNC:25489	ENSG00000163872	Q9ULM3	YEATS domain-containing protein 2	gencc,clinvar
CNTN2	HGNC:2172	ENSG00000184144	Q02246	Contactin-2	gencc
CTNND2	HGNC:2516	ENSG00000169862	Q9UQB3	Catenin delta-2	gencc
ADRA2B	HGNC:282	ENSG00000274286	P18089	Alpha-2B adrenergic receptor	gencc
MARCHF6	HGNC:30550	ENSG00000145495	O60337	E3 ubiquitin-protein ligase MARCHF6	gencc
SAMD12	HGNC:31750	ENSG00000177570	Q8N8I0	Sterile alpha motif domain-containing protein 12	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YEATS2	YEATS domain-containing protein 2	Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.
CNTN2	Contactin-2	In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region.
CTNND2	Catenin delta-2	Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses.
ADRA2B	Alpha-2B adrenergic receptor	Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression.
MARCHF6	E3 ubiquitin-protein ligase MARCHF6	Endoplasmic reticulum membrane-associated E3 ubiquitin ligase that plays a critical role in mitigating endoplasmic reticulum stress, the regulation of cholesterol and lipid homeostasis, and ferroptosis.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · 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
Antibody/Immunoglobulin	1	4.9×	0.452
GPCR	1	4.0×	0.452
Transcription factor	1	1.4×	0.719
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
YEATS2	Other/Unknown	no		YEATS, YEAST_sf, YEATS2_3HBD
CNTN2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
CTNND2	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold
ADRA2B	GPCR	yes		ADRA2B_rcpt, GPCR_Rhodpsn, ADR_fam
MARCHF6	Transcription factor	no	2.3.2.27	Znf_RING-CH, Znf_RING/FYVE/PHD, MARCHF6-like_C
SAMD12	Other/Unknown	no		SAM, SAM/pointed_sf, Aveugle-like_SAM_dom

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	2
buccal mucosa cell	1
ganglionic eminence	1
C1 segment of cervical spinal cord	1
corpus callosum	1
inferior vagus X ganglion	1
amygdala	1
cortical plate	1
prefrontal cortex	1
apex of heart	1
gastrocnemius	1
tendon of biceps brachii	1
Brodmann (1909) area 23	1
gluteal muscle	1
bone marrow cell	1
colonic epithelium	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
YEATS2	283	ubiquitous	marker	buccal mucosa cell, endothelial cell, ganglionic eminence
CNTN2	190	broad	marker	inferior vagus X ganglion, C1 segment of cervical spinal cord, corpus callosum
CTNND2	213	broad	marker	cortical plate, prefrontal cortex, amygdala
ADRA2B	147	broad	marker	apex of heart, tendon of biceps brachii, gastrocnemius
MARCHF6	302	ubiquitous	marker	Brodmann (1909) area 23, endothelial cell, gluteal muscle
SAMD12	167	ubiquitous	marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YEATS2	2,548
CTNND2	2,437
MARCHF6	1,609
ADRA2B	962
SAMD12	590
CNTN2	32

Intra-cohort edges

A	B	Sources
CTNND2	SAMD12	string_interaction
MARCHF6	SAMD12	string_interaction
SAMD12	YEATS2	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
YEATS2	Q9ULM3	5
CNTN2	Q02246	5
ADRA2B	P18089	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MARCHF6	O60337	78.23
SAMD12	Q8N8I0	72.09
CTNND2	Q9UQB3	58.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Adrenaline signalling through Alpha-2 adrenergic receptor	1	951.7×	0.025	ADRA2B
NrCAM interactions	1	407.9×	0.025	CNTN2
Adrenoceptors	1	317.2×	0.025	ADRA2B
Calnexin/calreticulin cycle	1	178.4×	0.032	MARCHF6
ER Quality Control Compartment (ERQC)	1	135.9×	0.032	MARCHF6
Platelet Aggregation (Plug Formation)	1	109.8×	0.032	ADRA2B
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	105.7×	0.032	MARCHF6
Amine ligand-binding receptors	1	86.5×	0.035	ADRA2B
Formation of WDR5-containing histone-modifying complexes	1	66.4×	0.037	YEATS2
NCAM1 interactions	1	62.1×	0.037	CNTN2
G alpha (z) signalling events	1	58.3×	0.037	ADRA2B
L1CAM interactions	1	30.1×	0.066	CNTN2
Platelet activation, signaling and aggregation	1	26.4×	0.069	ADRA2B
HATs acetylate histones	1	19.8×	0.085	YEATS2
Class A/1 (Rhodopsin-like receptors)	1	18.5×	0.085	ADRA2B
GPCR ligand binding	1	16.0×	0.091	ADRA2B
Asparagine N-linked glycosylation	1	15.0×	0.092	MARCHF6
GPCR downstream signalling	1	10.9×	0.119	ADRA2B
Signaling by GPCR	1	10.0×	0.119	ADRA2B
G alpha (i) signalling events	1	9.7×	0.119	ADRA2B
Hemostasis	1	9.0×	0.122	ADRA2B
Post-translational protein modification	1	4.8×	0.210	MARCHF6
Metabolism of proteins	1	3.1×	0.299	MARCHF6
Signal Transduction	1	2.5×	0.339	ADRA2B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
establishment of protein localization to juxtaparanode region of axon	1	2808.7×	0.008	CNTN2
presynaptic membrane organization	1	2808.7×	0.008	CNTN2
synapse organization	2	93.6×	0.008	CNTN2, CTNND2
regulation of astrocyte differentiation	1	936.2×	0.010	CNTN2
positive regulation of adenosine receptor signaling pathway	1	936.2×	0.010	CNTN2
clustering of voltage-gated potassium channels	1	702.2×	0.010	CNTN2
protein localization to juxtaparanode region of axon	1	702.2×	0.010	CNTN2
regulation of vascular associated smooth muscle contraction	1	561.7×	0.010	ADRA2B
regulation of axon diameter	1	561.7×	0.010	CNTN2
negative regulation of epinephrine secretion	1	561.7×	0.010	ADRA2B
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	1	561.7×	0.010	ADRA2B
negative regulation of norepinephrine secretion	1	468.1×	0.011	ADRA2B
cerebral cortex GABAergic interneuron migration	1	468.1×	0.011	CNTN2
G protein-coupled adenosine receptor signaling pathway	1	401.2×	0.011	CNTN2
negative regulation of cholesterol biosynthetic process	1	401.2×	0.011	MARCHF6
positive regulation of uterine smooth muscle contraction	1	351.1×	0.011	ADRA2B
adrenergic receptor signaling pathway	1	312.1×	0.012	ADRA2B
reduction of food intake in response to dietary excess	1	280.9×	0.013	CNTN2
positive regulation of protein processing	1	200.6×	0.016	CNTN2
endoplasmic reticulum mannose trimming	1	200.6×	0.016	MARCHF6
positive regulation of blood pressure	1	175.5×	0.017	ADRA2B
dendrite self-avoidance	1	175.5×	0.017	CNTN2
central nervous system myelination	1	165.2×	0.017	CNTN2
axonal fasciculation	1	156.0×	0.017	CNTN2
dendritic spine morphogenesis	1	147.8×	0.017	CTNND2
proteasomal protein catabolic process	1	127.7×	0.019	MARCHF6
regulation of cell division	1	127.7×	0.019	YEATS2
regulation of neuronal synaptic plasticity	1	112.3×	0.020	CNTN2
regulation of cell morphogenesis	1	104.0×	0.021	CNTN2
cell adhesion	2	12.5×	0.021	CNTN2, CTNND2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 6 evidence-associated genes (33%) 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
ADRA2B	BEPRIDIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADRA2B	316	4
YEATS2	0	0
CNTN2	0	0
CTNND2	0	0
MARCHF6	0	0
SAMD12	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	ADRA2B
CANDESARTAN CILEXETIL	4	ADRA2B
CLOTRIMAZOLE	4	ADRA2B
SIMVASTATIN	4	ADRA2B
METHYSERGIDE	4	ADRA2B
TIZANIDINE	4	ADRA2B
SUVOREXANT	4	ADRA2B
ACETOPHENAZINE	4	ADRA2B
IMIPRAMINE	4	ADRA2B
DROPERIDOL	4	ADRA2B
RIMONABANT	4	ADRA2B
ARIPIPRAZOLE	4	ADRA2B
AMOXAPINE	4	ADRA2B
IDARUBICIN	4	ADRA2B
PONATINIB	4	ADRA2B
DESLORATADINE	4	ADRA2B
AFATINIB	4	ADRA2B
DULOXETINE	4	ADRA2B
CELECOXIB	4	ADRA2B
DIETHYLPROPION	4	ADRA2B
DIMENHYDRINATE	4	ADRA2B
NEFAZODONE HYDROCHLORIDE	4	ADRA2B
DIHYDROERGOTAMINE MESYLATE	4	ADRA2B
AZELASTINE HYDROCHLORIDE	4	ADRA2B
THIOTHIXENE	4	ADRA2B
BENZTHIAZIDE	4	ADRA2B
CABERGOLINE	4	ADRA2B
BENZTROPINE	4	ADRA2B
PROPIOMAZINE	4	ADRA2B
DAPIPRAZOLE	4	ADRA2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ADRA2B	596	Binding:466, Functional:123, ADMET:5, Unclassified:2
YEATS2	11	Binding:11

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MARCHF6	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ADRA2B	596

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	ADRA2B
CANDESARTAN CILEXETIL	4	ADRA2B
CLOTRIMAZOLE	4	ADRA2B
SIMVASTATIN	4	ADRA2B
METHYSERGIDE	4	ADRA2B
TIZANIDINE	4	ADRA2B
SUVOREXANT	4	ADRA2B
ACETOPHENAZINE	4	ADRA2B
IMIPRAMINE	4	ADRA2B
DROPERIDOL	4	ADRA2B
RIMONABANT	4	ADRA2B
ARIPIPRAZOLE	4	ADRA2B
AMOXAPINE	4	ADRA2B
IDARUBICIN	4	ADRA2B
PONATINIB	4	ADRA2B
DESLORATADINE	4	ADRA2B
AFATINIB	4	ADRA2B
DULOXETINE	4	ADRA2B
CELECOXIB	4	ADRA2B
DIETHYLPROPION	4	ADRA2B
DIMENHYDRINATE	4	ADRA2B
NEFAZODONE HYDROCHLORIDE	4	ADRA2B
DIHYDROERGOTAMINE MESYLATE	4	ADRA2B
AZELASTINE HYDROCHLORIDE	4	ADRA2B
THIOTHIXENE	4	ADRA2B
BENZTHIAZIDE	4	ADRA2B
CABERGOLINE	4	ADRA2B
BENZTROPINE	4	ADRA2B
PROPIOMAZINE	4	ADRA2B
DAPIPRAZOLE	4	ADRA2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ADRA2B
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CNTN2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	YEATS2, CTNND2, MARCHF6, SAMD12

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
YEATS2	11	—
CNTN2	0	—
CTNND2	0	—
MARCHF6	0	—
SAMD12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.