Epilepsy, familial adult myoclonic, 1

Summary

Epilepsy, familial adult myoclonic, 1 (MONDO:0010985) is a disease caused by SAMD12 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SAMD12 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, familial adult myoclonic, 1
Mondo ID	MONDO:0010985
MeSH	C563399
OMIM	601068
DOID	DOID:0111690
UMLS	C1832841
MedGen	371424
GARD	0018082
Is cancer (heuristic)	no

Also known as: FAME1

Data availability: 6 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, 1

Related subtypes (7): 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, 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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
560216	SAMD12, 5-BP INS, TTTCA(n) REPEAT EXPANSION, IVS4	SAMD12	Pathogenic	no assertion criteria provided
800660	NC_000008.10:g.119379055_119379157TGAAA[100_?]TAAAA[40_?]	SAMD12	Pathogenic	no assertion criteria provided
872917	NC_000008.10:g.119379055_119379157TGAAA[149]TAAAA[446]	SAMD12	Pathogenic	no assertion criteria provided
474466	NM_005076.5(CNTN2):c.1695G>A (p.Val565=)	CNTN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1696749	NM_207506.3(SAMD12):c.13+16544C>A	SAMD12	Uncertain significance	criteria provided, single submitter
3067929	NM_207506.3(SAMD12):c.362G>T (p.Arg121Leu)	SAMD12	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
SAMD12	Strong	Autosomal dominant	epilepsy, familial adult myoclonic, 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SAMD12	Orphanet:86814	Familial adult myoclonic epilepsy
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
SAMD12	HGNC:31750	ENSG00000177570	Q8N8I0	Sterile alpha motif domain-containing protein 12	gencc,clinvar
CNTN2	HGNC:2172	ENSG00000184144	Q02246	Contactin-2	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.

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)
SAMD12	Other/Unknown	no		SAM, SAM/pointed_sf, Aveugle-like_SAM_dom
CNTN2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom

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
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
C1 segment of cervical spinal cord	1
corpus callosum	1
inferior vagus X ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SAMD12	167	ubiquitous	marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell
CNTN2	190	broad	marker	inferior vagus X ganglion, C1 segment of cervical spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SAMD12	590
CNTN2	32

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNTN2	Q02246	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SAMD12	Q8N8I0	72.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
NrCAM interactions	1	1631.4×	0.002	CNTN2
NCAM1 interactions	1	248.3×	0.006	CNTN2
L1CAM interactions	1	120.2×	0.008	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×	0.002	CNTN2
presynaptic membrane organization	1	8426.0×	0.002	CNTN2
regulation of astrocyte differentiation	1	2808.7×	0.002	CNTN2
positive regulation of adenosine receptor signaling pathway	1	2808.7×	0.002	CNTN2
clustering of voltage-gated potassium channels	1	2106.5×	0.002	CNTN2
protein localization to juxtaparanode region of axon	1	2106.5×	0.002	CNTN2
regulation of axon diameter	1	1685.2×	0.002	CNTN2
cerebral cortex GABAergic interneuron migration	1	1404.3×	0.003	CNTN2
G protein-coupled adenosine receptor signaling pathway	1	1203.7×	0.003	CNTN2
reduction of food intake in response to dietary excess	1	842.6×	0.003	CNTN2
positive regulation of protein processing	1	601.9×	0.004	CNTN2
dendrite self-avoidance	1	526.6×	0.004	CNTN2
central nervous system myelination	1	495.6×	0.004	CNTN2
axonal fasciculation	1	468.1×	0.004	CNTN2
regulation of neuronal synaptic plasticity	1	337.0×	0.006	CNTN2
regulation of cell morphogenesis	1	312.1×	0.006	CNTN2
adult walking behavior	1	247.8×	0.007	CNTN2
receptor internalization	1	162.0×	0.010	CNTN2
learning	1	140.4×	0.010	CNTN2
synapse organization	1	140.4×	0.010	CNTN2
negative regulation of neuron differentiation	1	135.9×	0.010	CNTN2
fat cell differentiation	1	90.6×	0.014	CNTN2
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.014	SAMD12
protein processing	1	85.1×	0.014	CNTN2
establishment of localization in cell	1	80.2×	0.014	CNTN2
homophilic cell-cell adhesion	1	70.2×	0.016	CNTN2
microtubule cytoskeleton organization	1	60.6×	0.018	CNTN2
axon guidance	1	45.3×	0.023	CNTN2
cell adhesion	1	18.7×	0.053	CNTN2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
SAMD12	0	0
CNTN2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SAMD12

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)
SAMD12	0	—
CNTN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.