Epilepsy, familial adult myoclonic, 7

Summary

Epilepsy, familial adult myoclonic, 7 (MONDO:0054847) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 7
Mondo ID	MONDO:0054847
OMIM	618075
DOID	DOID:0111694
UMLS	C4748080
MedGen	1648435
GARD	0025987
Is cancer (heuristic)	no

Also known as: FAME7

Data availability: 12 ClinVar variants · 1 GenCC gene-disease record.

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, 7

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, benign adult familial myoclonic epilepsy, epilepsy, familial adult myoclonic, 6

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:

6 uncertain significance, 5 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
559389	RAPGEF2, 5-BP INS, TTTCA(n) REPEAT EXPANSION	RAPGEF2	Pathogenic	no assertion criteria provided
3065187	NM_001394067.2(RAPGEF2):c.53C>T (p.Pro18Leu)	LOC129993307	Uncertain significance	criteria provided, single submitter
3064560	NM_001394067.2(RAPGEF2):c.4975G>A (p.Ala1659Thr)	RAPGEF2	Uncertain significance	criteria provided, single submitter
3590437	NM_001394067.2(RAPGEF2):c.1761C>T (p.Gly587=)	RAPGEF2	Uncertain significance	criteria provided, single submitter
3590438	NM_001394067.2(RAPGEF2):c.2885G>A (p.Cys962Tyr)	RAPGEF2	Uncertain significance	criteria provided, single submitter
982725	NM_001394067.2(RAPGEF2):c.4958-8A>G	RAPGEF2	Uncertain significance	criteria provided, single submitter
996945	NM_001394067.2(RAPGEF2):c.819G>C (p.Glu273Asp)	RAPGEF2	Uncertain significance	criteria provided, single submitter
1327937	NM_001394067.2(RAPGEF2):c.282-12C>A	RAPGEF2	Benign	criteria provided, multiple submitters, no conflicts
1327938	NM_001394067.2(RAPGEF2):c.1303-68TG[16]	RAPGEF2	Benign	criteria provided, single submitter
1327939	NM_001394067.2(RAPGEF2):c.1303-68TG[17]	RAPGEF2	Benign	criteria provided, single submitter
1327940	NM_001394067.2(RAPGEF2):c.3713-10del	RAPGEF2	Benign	criteria provided, single submitter
1327941	NM_001394067.2(RAPGEF2):c.4923C>T (p.Pro1641=)	RAPGEF2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
RAPGEF2	Limited	Autosomal dominant	epilepsy, familial adult myoclonic, 7	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAPGEF2	Orphanet:86814	Familial adult myoclonic epilepsy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAPGEF2	HGNC:16854	ENSG00000109756	Q9Y4G8	Rap guanine nucleotide exchange factor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAPGEF2	Rap guanine nucleotide exchange factor 2	Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAPGEF2	Scaffold/PPI	no		RA_dom, cNMP-bd_dom, Ras-like_Gua-exchang_fac_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAPGEF2	297	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAPGEF2	1,467

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAPGEF2	Q9Y4G8	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MAPK1/MAPK3 signaling	1	131.3×	0.019	RAPGEF2
MAPK family signaling cascades	1	102.9×	0.019	RAPGEF2
RAF/MAP kinase cascade	1	61.1×	0.022	RAPGEF2
Signal Transduction	1	10.2×	0.098	RAPGEF2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cAMP-dependent protein kinase activity	1	8426.0×	0.002	RAPGEF2
positive regulation of dendritic cell apoptotic process	1	4213.0×	0.002	RAPGEF2
brain-derived neurotrophic factor receptor signaling pathway	1	3370.4×	0.002	RAPGEF2
positive regulation of microvillus assembly	1	3370.4×	0.002	RAPGEF2
forebrain neuron development	1	2407.4×	0.002	RAPGEF2
negative regulation of melanin biosynthetic process	1	2407.4×	0.002	RAPGEF2
regulation of cell junction assembly	1	2407.4×	0.002	RAPGEF2
cellular response to cGMP	1	2106.5×	0.002	RAPGEF2
microvillus assembly	1	1872.4×	0.002	RAPGEF2
positive regulation of protein binding	1	1872.4×	0.002	RAPGEF2
negative regulation of dendrite morphogenesis	1	1872.4×	0.002	RAPGEF2
Rap protein signal transduction	1	1685.2×	0.002	RAPGEF2
establishment of endothelial intestinal barrier	1	1404.3×	0.002	RAPGEF2
nerve growth factor signaling pathway	1	1296.3×	0.002	RAPGEF2
positive regulation of vasculogenesis	1	1296.3×	0.002	RAPGEF2
adenylate cyclase-activating adrenergic receptor signaling pathway	1	1203.7×	0.002	RAPGEF2
positive regulation of neuron migration	1	991.3×	0.002	RAPGEF2
ventricular system development	1	842.6×	0.003	RAPGEF2
establishment of endothelial barrier	1	766.0×	0.003	RAPGEF2
positive regulation of protein kinase activity	1	674.1×	0.003	RAPGEF2
cellular response to nerve growth factor stimulus	1	468.1×	0.004	RAPGEF2
blood vessel development	1	374.5×	0.005	RAPGEF2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	337.0×	0.005	RAPGEF2
cellular response to cAMP	1	290.6×	0.005	RAPGEF2
positive regulation of GTPase activity	1	276.3×	0.006	RAPGEF2
regulation of synaptic plasticity	1	259.3×	0.006	RAPGEF2
Ras protein signal transduction	1	205.5×	0.007	RAPGEF2
small GTPase-mediated signal transduction	1	183.2×	0.007	RAPGEF2
neuropeptide signaling pathway	1	172.0×	0.008	RAPGEF2
MAPK cascade	1	153.2×	0.008	RAPGEF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAPGEF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	RAPGEF2

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)
RAPGEF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.