Epilepsy, idiopathic generalized, susceptibility to, 11

Summary

Epilepsy, idiopathic generalized, susceptibility to, 11 (MONDO:0011875) is a disease caused by CLCN2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CLCN2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 175

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epilepsy, idiopathic generalized, susceptibility to, 11
Mondo ID	MONDO:0011875
OMIM	607628
DOID	DOID:0111312
UMLS	C2750893
MedGen	416407
Is cancer (heuristic)	no

Also known as: CLCN2 generalised epilepsy · CLCN2 generalized epilepsy · EIG11 · epilepsy, idiopathic generalized, susceptibility to, 11 · epilepsy, idiopathic generalized, susceptibility to, type 11 · generalised epilepsy caused by mutation in CLCN2 · generalized epilepsy caused by mutation in CLCN2 · susceptibility to idiopathic generalised epilepsy 11

Data availability: 175 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › epilepsy, juvenile absence, susceptibility to › epilepsy, idiopathic generalized, susceptibility to, 11

Related subtypes (1): epilepsy, juvenile absence, susceptibility to, 1

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

175 retrieved; paginated sample, class counts are floors:

122 uncertain significance, 18 conflicting classifications of pathogenicity, 13 likely benign, 8 benign/likely benign, 7 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
100629	NM_004366.6(CLCN2):c.1709G>A (p.Trp570Ter)	CLCN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1279936	NM_004366.6(CLCN2):c.668_672del (p.Leu223fs)	CLCN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217788	NM_004366.6(CLCN2):c.1143del (p.Gly382fs)	CLCN2	Pathogenic	criteria provided, multiple submitters, no conflicts
2724374	NM_004366.6(CLCN2):c.1828C>T (p.Arg610Ter)	CLCN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
441164	NM_004366.6(CLCN2):c.515G>A (p.Arg172Gln)	CLCN2	Pathogenic	criteria provided, multiple submitters, no conflicts
1194517	NM_004366.6(CLCN2):c.898+1G>A	CLCN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300131	NM_004366.6(CLCN2):c.1550C>T (p.Thr517Met)	CLCN2	Likely pathogenic	criteria provided, single submitter
217785	NM_004366.6(CLCN2):c.925C>T (p.Arg309Ter)	CLCN2	Likely pathogenic	criteria provided, single submitter
3589028	NM_004366.6(CLCN2):c.1069del (p.Arg357fs)	CLCN2	Likely pathogenic	criteria provided, single submitter
3589053	NM_004366.6(CLCN2):c.221-2A>G	CLCN2	Likely pathogenic	criteria provided, single submitter
3589056	NM_004366.6(CLCN2):c.194del (p.Gly65fs)	CLCN2	Likely pathogenic	criteria provided, single submitter
3589059	NM_004366.6(CLCN2):c.64-1G>A	CLCN2	Likely pathogenic	criteria provided, single submitter
1106292	NM_004366.6(CLCN2):c.1067A>G (p.Asn356Ser)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1315588	NM_004366.6(CLCN2):c.1969A>C (p.Thr657Pro)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1394236	NM_004366.6(CLCN2):c.2174G>A (p.Arg725Gln)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1621558	NM_004366.6(CLCN2):c.2657G>A (p.Arg886Gln)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1958391	NM_004366.6(CLCN2):c.63+4A>G	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1959620	NM_004366.6(CLCN2):c.220+15G>A	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2040196	NM_004366.6(CLCN2):c.773-9C>G	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2040248	NM_004366.6(CLCN2):c.2425A>G (p.Ile809Val)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2082041	NM_004366.6(CLCN2):c.2197C>T (p.Pro733Ser)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2174239	NM_004366.6(CLCN2):c.2399G>A (p.Arg800Gln)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217771	NM_004366.6(CLCN2):c.246C>G (p.Phe82Leu)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217773	NM_004366.6(CLCN2):c.1856-3C>T	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217794	NM_004366.6(CLCN2):c.1795G>A (p.Asp599Asn)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3589003	NM_004366.6(CLCN2):c.1932C>T (p.Arg644=)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3589035	NM_004366.6(CLCN2):c.819G>T (p.Arg273=)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772363	NM_004366.6(CLCN2):c.1141C>G (p.Pro381Ala)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9038	NM_004366.6(CLCN2):c.704G>A (p.Arg235Gln)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9039	NM_004366.6(CLCN2):c.1730G>A (p.Arg577Gln)	CLCN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
CLCN2	Strong	Autosomal dominant	epilepsy, idiopathic generalized, susceptibility to, 11	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLCN2	Orphanet:307	Juvenile myoclonic epilepsy
CLCN2	Orphanet:363540	Leukoencephalopathy with mild cerebellar ataxia and white matter edema
CLCN2	Orphanet:404	Familial hyperaldosteronism type II

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
CLCN2	HGNC:2020	ENSG00000114859	P51788	Chloride channel protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLCN2	Chloride channel protein 2	Voltage-gated and osmosensitive chloride channel.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLCN2	Other/Unknown	no		ClC, Cl-channel-2, Cl-channel_core

Expression context

Cohort genes with no expression data: 0.

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
mucosa of transverse colon	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLCN2	181	broad	yes	mucosa of transverse colon, tibial nerve, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLCN2	1,250

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLCN2	P51788	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Stimuli-sensing channels	1	135.9×	0.007	CLCN2

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
regulation of aldosterone biosynthetic process	1	16852.0×	5e-04	CLCN2
cell differentiation involved in salivary gland development	1	8426.0×	5e-04	CLCN2
regulation of membrane depolarization during action potential	1	8426.0×	5e-04	CLCN2
stabilization of membrane potential	1	5617.3×	5e-04	CLCN2
acinar cell differentiation	1	3370.4×	7e-04	CLCN2
cellular hypotonic response	1	1404.3×	0.001	CLCN2
regulation of resting membrane potential	1	1296.3×	0.001	CLCN2
phagocytosis, engulfment	1	674.1×	0.002	CLCN2
positive regulation of oligodendrocyte differentiation	1	674.1×	0.002	CLCN2
chloride transport	1	455.5×	0.003	CLCN2
retina development in camera-type eye	1	255.3×	0.004	CLCN2
lung development	1	198.3×	0.005	CLCN2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CLCN2	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
CLCN2	1	Binding:1

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	CLCN2

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)
CLCN2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.