Epilepsy, familial adult myoclonic, 5

Summary

Epilepsy, familial adult myoclonic, 5 (MONDO:0014167) is a disease caused by CNTN2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CNTN2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 829

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 5
Mondo ID	MONDO:0014167
OMIM	615400
DOID	DOID:0111691
UMLS	C3809374
MedGen	815704
GARD	0018086
Is cancer (heuristic)	no

Also known as: CNTN2 epilepsy, familial adult myoclonic · cortical myoclonic tremor with epilepsy, familial, 5 · epilepsy, familial adult myoclonic caused by mutation in CNTN2 · epilepsy, familial adult myoclonic, 5 · epilepsy, familial adult myoclonic, type 5 · epilepsy, myoclonic, familial adult, 5 · FAME5

Data availability: 829 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, 5

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

600 retrieved; paginated sample, class counts are floors:

328 likely benign, 223 uncertain significance, 18 pathogenic, 13 benign, 8 likely pathogenic, 7 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069884	NM_005076.5(CNTN2):c.2587C>T (p.Arg863Ter)	CNTN2	Pathogenic	criteria provided, single submitter
1367262	NM_005076.5(CNTN2):c.2773del (p.Ser925fs)	CNTN2	Pathogenic	criteria provided, single submitter
1406570	NM_005076.5(CNTN2):c.1180C>T (p.Gln394Ter)	CNTN2	Pathogenic	criteria provided, single submitter
1424788	NM_005076.5(CNTN2):c.2740C>T (p.Arg914Ter)	CNTN2	Pathogenic	criteria provided, single submitter
1456315	NM_005076.5(CNTN2):c.2697dup (p.Ser900fs)	CNTN2	Pathogenic	criteria provided, single submitter
1526248	NM_005076.5(CNTN2):c.1699G>T (p.Glu567Ter)	CNTN2	Pathogenic	criteria provided, single submitter
1939902	NM_005076.5(CNTN2):c.418C>T (p.Arg140Ter)	CNTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2111360	NM_005076.5(CNTN2):c.851G>A (p.Trp284Ter)	CNTN2	Pathogenic	criteria provided, single submitter
2190542	NM_005076.5(CNTN2):c.2193G>A (p.Trp731Ter)	CNTN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2425292	NC_000001.10:g.(?205022314)(205042893_?)del	CNTN2	Pathogenic	criteria provided, single submitter
2767108	NM_005076.5(CNTN2):c.1327dup (p.Arg443fs)	CNTN2	Pathogenic	criteria provided, single submitter
2808573	NM_005076.5(CNTN2):c.2081_2099del (p.Gly694fs)	CNTN2	Pathogenic	criteria provided, single submitter
2809835	NM_005076.5(CNTN2):c.124C>T (p.Gln42Ter)	CNTN2	Pathogenic	criteria provided, single submitter
2826422	NM_005076.5(CNTN2):c.766C>T (p.Gln256Ter)	CNTN2	Pathogenic	criteria provided, single submitter
2826844	NM_005076.5(CNTN2):c.2067_2068del (p.Ile690fs)	CNTN2	Pathogenic	criteria provided, single submitter
2888349	NM_005076.5(CNTN2):c.159_160delinsTT (p.Glu54Ter)	CNTN2	Pathogenic	criteria provided, single submitter
3233305	NM_005076.5(CNTN2):c.2874_2875del (p.Pro959fs)	CNTN2	Pathogenic	no assertion criteria provided
3638617	NM_005076.5(CNTN2):c.1884G>A (p.Trp628Ter)	CNTN2	Pathogenic	criteria provided, single submitter
3661528	NM_005076.5(CNTN2):c.1696A>T (p.Lys566Ter)	CNTN2	Pathogenic	criteria provided, single submitter
3701041	NM_005076.5(CNTN2):c.1711del (p.Asp571fs)	CNTN2	Pathogenic	criteria provided, single submitter
1068043	NM_005076.5(CNTN2):c.2731+1G>A	CNTN2	Likely pathogenic	criteria provided, single submitter
1468336	NM_005076.5(CNTN2):c.1695+2T>C	CNTN2	Likely pathogenic	criteria provided, single submitter
1484408	NM_005076.5(CNTN2):c.1240+1G>A	CNTN2	Likely pathogenic	criteria provided, single submitter
1515118	NM_005076.5(CNTN2):c.2126-1G>C	CNTN2	Likely pathogenic	criteria provided, single submitter
2096043	NM_005076.5(CNTN2):c.2197-2A>G	CNTN2	Likely pathogenic	criteria provided, single submitter
2127230	NM_005076.5(CNTN2):c.2544+1G>T	CNTN2	Likely pathogenic	criteria provided, single submitter
2697084	NM_005076.5(CNTN2):c.1696-2A>G	CNTN2	Likely pathogenic	criteria provided, single submitter
3247832	NC_000001.10:g.(?205034083)(205035624_?)del	CNTN2	Likely pathogenic	criteria provided, single submitter
1034153	NM_005076.5(CNTN2):c.2111G>A (p.Arg704Gln)	CNTN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1453751	NM_005076.5(CNTN2):c.1216G>A (p.Ala406Thr)	CNTN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CNTN2	Strong	Autosomal recessive	epilepsy, familial adult myoclonic, 5	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNTN2	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
CNTN2	HGNC:2172	ENSG00000184144	Q02246	Contactin-2	gencc,clinvar
ADIPOR1	HGNC:24040	ENSG00000159346	Q96A54	Adiponectin receptor protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
ADIPOR1	Adiponectin receptor protein 1	Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNTN2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
ADIPOR1	Other/Unknown	no		AdipoR/HlyIII-related

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
C1 segment of cervical spinal cord	1
corpus callosum	1
inferior vagus X ganglion	1
blood	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNTN2	190	broad	marker	inferior vagus X ganglion, C1 segment of cervical spinal cord, corpus callosum
ADIPOR1	286	ubiquitous	marker	blood, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADIPOR1	1,570
CNTN2	32

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNTN2	Q02246	5
ADIPOR1	Q96A54	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
NrCAM interactions	1	815.7×	0.003	CNTN2
AMPK inhibits chREBP transcriptional activation activity	1	713.8×	0.003	ADIPOR1
NCAM1 interactions	1	124.1×	0.011	CNTN2
L1CAM interactions	1	60.1×	0.017	CNTN2

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
establishment of protein localization to juxtaparanode region of axon	1	8426.0×	0.003	CNTN2
presynaptic membrane organization	1	8426.0×	0.003	CNTN2
regulation of astrocyte differentiation	1	2808.7×	0.003	CNTN2
positive regulation of adenosine receptor signaling pathway	1	2808.7×	0.003	CNTN2
clustering of voltage-gated potassium channels	1	2106.5×	0.003	CNTN2
protein localization to juxtaparanode region of axon	1	2106.5×	0.003	CNTN2
regulation of axon diameter	1	1685.2×	0.004	CNTN2
cerebral cortex GABAergic interneuron migration	1	1404.3×	0.004	CNTN2
G protein-coupled adenosine receptor signaling pathway	1	1203.7×	0.004	CNTN2
leptin-mediated signaling pathway	1	1203.7×	0.004	ADIPOR1
adiponectin-activated signaling pathway	1	1053.2×	0.004	ADIPOR1
reduction of food intake in response to dietary excess	1	842.6×	0.004	CNTN2
positive regulation of protein processing	1	601.9×	0.005	CNTN2
negative regulation of epithelial cell migration	1	526.6×	0.005	ADIPOR1
fatty acid oxidation	1	526.6×	0.005	ADIPOR1
dendrite self-avoidance	1	526.6×	0.005	CNTN2
central nervous system myelination	1	495.6×	0.005	CNTN2
axonal fasciculation	1	468.1×	0.005	CNTN2
negative regulation of receptor signaling pathway via JAK-STAT	1	443.5×	0.005	ADIPOR1
positive regulation of insulin receptor signaling pathway	1	421.3×	0.005	ADIPOR1
regulation of neuronal synaptic plasticity	1	337.0×	0.006	CNTN2
regulation of cell morphogenesis	1	312.1×	0.006	CNTN2
regulation of glucose metabolic process	1	280.9×	0.007	ADIPOR1
negative regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.007	ADIPOR1
adult walking behavior	1	247.8×	0.007	CNTN2
regulation of lipid metabolic process	1	216.1×	0.007	ADIPOR1
positive regulation of receptor signaling pathway via JAK-STAT	1	216.1×	0.007	ADIPOR1
negative regulation of epithelial to mesenchymal transition	1	205.5×	0.007	ADIPOR1
hormone-mediated signaling pathway	1	200.6×	0.007	ADIPOR1
receptor internalization	1	162.0×	0.009	CNTN2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CNTN2	0	0
ADIPOR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ADIPOR1	1	Binding:1

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

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	1	CNTN2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ADIPOR1

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)
CNTN2	0	—
ADIPOR1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.