Epilepsy, familial adult myoclonic, 2

Summary

Epilepsy, familial adult myoclonic, 2 (MONDO:0011930) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 2
Mondo ID	MONDO:0011930
MeSH	C564313
OMIM	607876
DOID	DOID:0111692
UMLS	C1842852
MedGen	375031
GARD	0018083
Is cancer (heuristic)	no

Also known as: ADRA2B epilepsy, familial adult myoclonic · epilepsy, familial adult myoclonic caused by mutation in ADRA2B · epilepsy, familial adult myoclonic, 2 · epilepsy, familial adult myoclonic, type 2 · FAME2

Data availability: 12 ClinVar variants · 2 GenCC gene-disease records.

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 › epilepsy, familial adult myoclonic, 2

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

12 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
635132	NM_020151.3(STARD7):c.291-1572_291-1518ATTTT[376]ATTTC[274]	STARD7	Pathogenic	no assertion criteria provided
694447	NC_000002.12:g.96197067AAAAT[(n)]/AAATG[(n)]	STARD7	Pathogenic	no assertion criteria provided
191117	NM_000682.7(ADRA2B):c.664C>T (p.Arg222Ter)	ADRA2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029933	NM_000682.7(ADRA2B):c.274G>A (p.Asp92Asn)	ADRA2B	Uncertain significance	criteria provided, single submitter
1032452	NM_000682.7(ADRA2B):c.649G>A (p.Glu217Lys)	ADRA2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
192366	NM_000682.7(ADRA2B):c.675_686delinsGTTTGGCAG (p.His225_Leu229delinsGlnPheGlyArg)	ADRA2B	Uncertain significance	no assertion criteria provided
992750	NM_000682.7(ADRA2B):c.898_899insGGGAAGAGG (p.Glu299_Glu300insGlyGluGlu)	ADRA2B	Uncertain significance	criteria provided, single submitter
1696639	NM_020151.4(STARD7):c.175G>T (p.Gly59Cys)	LOC129934328	Uncertain significance	criteria provided, single submitter
1342562	NM_020151.4(STARD7):c.361C>T (p.Pro121Ser)	STARD7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1701639	NM_020151.4(STARD7):c.418C>T (p.Arg140Cys)	STARD7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2346566	NM_020151.4(STARD7):c.899G>A (p.Arg300His)	STARD7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436504	NM_020151.4(STARD7):c.542A>G (p.Asn181Ser)	STARD7	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
ADRA2B	Supportive	Autosomal dominant	benign adult familial myoclonic epilepsy	4
STARD7	Limited	Autosomal dominant	epilepsy, familial adult myoclonic, 2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADRA2B	Orphanet:86814	Familial adult myoclonic epilepsy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STARD7	HGNC:18063	ENSG00000084090	Q9NQZ5	StAR-related lipid transfer protein 7, mitochondrial	gencc,clinvar
ADRA2B	HGNC:282	ENSG00000274286	P18089	Alpha-2B adrenergic receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STARD7	StAR-related lipid transfer protein 7, mitochondrial	May play a protective role in mucosal tissues by preventing exaggerated allergic responses.
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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STARD7	Other/Unknown	no		START_lipid-bd_dom, START-like_dom_sf, START_STARD7
ADRA2B	GPCR	yes		ADRA2B_rcpt, GPCR_Rhodpsn, ADR_fam

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
medial globus pallidus	1
oocyte	1
secondary oocyte	1
apex of heart	1
gastrocnemius	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STARD7	295	ubiquitous	marker	secondary oocyte, oocyte, medial globus pallidus
ADRA2B	147	broad	marker	apex of heart, tendon of biceps brachii, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STARD7	1,184
ADRA2B	962

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADRA2B	P18089	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STARD7	Q9NQZ5	75.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 2 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
Adrenaline signalling through Alpha-2 adrenergic receptor	1	1903.3×	0.012	ADRA2B
Metabolism of cofactors	1	951.7×	0.012	STARD7
Adrenoceptors	1	634.4×	0.012	ADRA2B
Ubiquinol biosynthesis	1	439.2×	0.013	STARD7
Platelet Aggregation (Plug Formation)	1	219.6×	0.017	ADRA2B
Synthesis of PC	1	203.9×	0.017	STARD7
Amine ligand-binding receptors	1	173.0×	0.017	ADRA2B
Glycerophospholipid biosynthesis	1	167.9×	0.017	STARD7
G alpha (z) signalling events	1	116.5×	0.022	ADRA2B
Phospholipid metabolism	1	100.2×	0.023	STARD7
Metabolism of vitamins and cofactors	1	58.3×	0.033	STARD7
Mitochondrial protein degradation	1	57.1×	0.033	STARD7
Platelet activation, signaling and aggregation	1	52.9×	0.033	ADRA2B
Class A/1 (Rhodopsin-like receptors)	1	37.1×	0.044	ADRA2B
GPCR ligand binding	1	32.1×	0.047	ADRA2B
GPCR downstream signalling	1	21.7×	0.065	ADRA2B
Signaling by GPCR	1	20.0×	0.065	ADRA2B
G alpha (i) signalling events	1	19.5×	0.065	ADRA2B
Hemostasis	1	18.0×	0.066	ADRA2B
Metabolism of lipids	1	15.8×	0.072	STARD7
Metabolism of proteins	1	6.2×	0.170	STARD7
Metabolism	1	5.8×	0.172	STARD7
Signal Transduction	1	5.1×	0.187	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
myeloid dendritic cell activation	1	2808.7×	0.003	STARD7
regulation of vascular associated smooth muscle contraction	1	1685.2×	0.003	ADRA2B
negative regulation of epinephrine secretion	1	1685.2×	0.003	ADRA2B
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	1	1685.2×	0.003	ADRA2B
negative regulation of norepinephrine secretion	1	1404.3×	0.003	ADRA2B
positive regulation of uterine smooth muscle contraction	1	1053.2×	0.003	ADRA2B
type 2 immune response	1	936.2×	0.003	STARD7
adrenergic receptor signaling pathway	1	936.2×	0.003	ADRA2B
mucociliary clearance	1	648.1×	0.004	STARD7
positive regulation of blood pressure	1	526.6×	0.004	ADRA2B
ubiquinone biosynthetic process	1	468.1×	0.004	STARD7
establishment of skin barrier	1	227.7×	0.008	STARD7
platelet activation	1	133.8×	0.013	ADRA2B
epidermal growth factor receptor signaling pathway	1	123.9×	0.013	ADRA2B
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	109.4×	0.013	ADRA2B
female pregnancy	1	105.3×	0.013	ADRA2B
positive regulation of neuron differentiation	1	99.1×	0.013	ADRA2B
positive regulation of MAPK cascade	1	40.3×	0.029	ADRA2B
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.029	ADRA2B
cell-cell signaling	1	34.8×	0.031	ADRA2B
inflammatory response	1	18.9×	0.054	STARD7
G protein-coupled receptor signaling pathway	1	18.1×	0.054	ADRA2B

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
STARD7	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): 0.

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

Symbol	Assays	Type breakdown
ADRA2B	596	Binding:466, Functional:123, ADMET:5, Unclassified:2
STARD7	3	Binding:3

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: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	STARD7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STARD7	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.