Autosomal dominant nocturnal frontal lobe epilepsy 3

Summary

Autosomal dominant nocturnal frontal lobe epilepsy 3 (MONDO:0011545) is a disease caused by CHRNB2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CHRNB2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant nocturnal frontal lobe epilepsy 3
Mondo ID	MONDO:0011545
MeSH	C565334
OMIM	605375
DOID	DOID:0060684
UMLS	C1854335
MedGen	344263
GARD	0015380
Is cancer (heuristic)	no

Also known as: autosomal dominant nocturnal frontal lobe epilepsy caused by mutation in CHRNB2 · autosomal dominant nocturnal frontal lobe epilepsy type 3 · CHRNB2 autosomal dominant nocturnal frontal lobe epilepsy · ENFL3 · epilepsy, nocturnal frontal lobe, 3 · epilepsy, nocturnal frontal lobe, type 3

Data availability: 41 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › focal epilepsy › familial partial epilepsy › familial sleep-related hypermotor epilepsy › autosomal dominant nocturnal frontal lobe epilepsy 3

Related subtypes (4): autosomal dominant nocturnal frontal lobe epilepsy 1, autosomal dominant nocturnal frontal lobe epilepsy 2, autosomal dominant nocturnal frontal lobe epilepsy 4, autosomal dominant nocturnal frontal lobe epilepsy 5

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

41 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 6 benign/likely benign, 6 conflicting classifications of pathogenicity, 2 likely pathogenic, 2 pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1707538	NM_000748.3(CHRNB2):c.859G>T (p.Val287Leu)	CHRNB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17495	NM_000748.3(CHRNB2):c.859G>C (p.Val287Leu)	CHRNB2	Pathogenic	criteria provided, multiple submitters, no conflicts
17496	NM_000748.3(CHRNB2):c.859G>A (p.Val287Met)	CHRNB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1030889	NM_000748.3(CHRNB2):c.845T>A (p.Leu282His)	CHRNB2	Likely pathogenic	criteria provided, single submitter
3061958	NM_000748.3(CHRNB2):c.256-1G>A	CHRNB2	Likely pathogenic	criteria provided, single submitter
158330	NM_000748.3(CHRNB2):c.1191G>C (p.Gln397His)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197695	NM_000748.3(CHRNB2):c.1046T>C (p.Met349Thr)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205066	NM_000748.3(CHRNB2):c.329A>C (p.Lys110Thr)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205069	NM_000748.3(CHRNB2):c.640G>A (p.Glu214Lys)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205077	NM_000748.3(CHRNB2):c.360CAA[1] (p.Asn122del)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
420432	NM_000748.3(CHRNB2):c.122G>A (p.Arg41His)	CHRNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1912617	NM_000748.3(CHRNB2):c.1111_1118del (p.Glu371fs)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
205062	NM_000748.3(CHRNB2):c.140G>A (p.Arg47His)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
205065	NM_000748.3(CHRNB2):c.317G>A (p.Arg106Gln)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
205078	NM_000748.3(CHRNB2):c.1129TTC[1] (p.Phe378del)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440037	NM_000748.3(CHRNB2):c.1333C>G (p.Gln445Glu)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2688781	NM_000748.3(CHRNB2):c.65G>A (p.Gly22Glu)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3250449	NM_000748.3(CHRNB2):c.821T>A (p.Leu274Gln)	CHRNB2	Uncertain significance	criteria provided, single submitter
373511	NM_000748.3(CHRNB2):c.373G>A (p.Gly125Ser)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3895490	NM_000748.3(CHRNB2):c.848T>A (p.Ile283Asn)	CHRNB2	Uncertain significance	criteria provided, single submitter
392288	NM_000748.3(CHRNB2):c.1320C>A (p.Ser440Arg)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
423390	NM_000748.3(CHRNB2):c.1291G>C (p.Val431Leu)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
430409	NM_000748.3(CHRNB2):c.1338+3G>T	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4530637	NM_000748.3(CHRNB2):c.635G>A (p.Arg212His)	CHRNB2	Uncertain significance	criteria provided, single submitter
543531	NM_000748.3(CHRNB2):c.734del (p.Cys245fs)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
566514	NM_000748.3(CHRNB2):c.106C>T (p.Leu36Phe)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
578261	NM_000748.3(CHRNB2):c.1319G>A (p.Ser440Asn)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
585666	NM_000748.3(CHRNB2):c.515A>G (p.Lys172Arg)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
641814	NM_000748.3(CHRNB2):c.1103G>T (p.Arg368Leu)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts
840970	NM_000748.3(CHRNB2):c.919C>A (p.Leu307Ile)	CHRNB2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
CHRNB2	Strong	Autosomal dominant	autosomal dominant nocturnal frontal lobe epilepsy 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRNB2	Orphanet:98784	Sleep-related hypermotor 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
CHRNB2	HGNC:1962	ENSG00000160716	P17787	Neuronal acetylcholine receptor subunit beta-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRNB2	Neuronal acetylcholine receptor subunit beta-2	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…

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)
CHRNB2	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel

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
cervix squamous epithelium	1
tongue squamous epithelium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRNB2	208	broad	yes	tongue squamous epithelium, cervix squamous epithelium, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRNB2	1,547

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHRNB2	P17787	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	1	1631.4×	0.002	CHRNB2
Highly calcium permeable nicotinic acetylcholine receptors	1	1268.9×	0.002	CHRNB2
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	1	1038.2×	0.002	CHRNB2
Presynaptic nicotinic acetylcholine receptors	1	951.7×	0.002	CHRNB2
Acetylcholine binding and downstream events	1	815.7×	0.002	CHRNB2
Postsynaptic nicotinic acetylcholine receptors	1	815.7×	0.002	CHRNB2
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.013	CHRNB2
Transmission across Chemical Synapses	1	76.1×	0.015	CHRNB2
Neuronal System	1	44.3×	0.023	CHRNB2

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
lateral geniculate nucleus development	1	16852.0×	0.002	CHRNB2
regulation of circadian sleep/wake cycle, REM sleep	1	8426.0×	0.002	CHRNB2
vestibulocochlear nerve development	1	5617.3×	0.002	CHRNB2
regulation of synaptic transmission, dopaminergic	1	4213.0×	0.002	CHRNB2
negative regulation of action potential	1	4213.0×	0.002	CHRNB2
synaptic transmission involved in micturition	1	4213.0×	0.002	CHRNB2
optic nerve morphogenesis	1	3370.4×	0.002	CHRNB2
response to acetylcholine	1	2106.5×	0.002	CHRNB2
central nervous system projection neuron axonogenesis	1	1872.4×	0.002	CHRNB2
behavioral response to nicotine	1	1872.4×	0.002	CHRNB2
positive regulation of dopamine secretion	1	1685.2×	0.002	CHRNB2
regulation of dopamine metabolic process	1	1685.2×	0.002	CHRNB2
regulation of dopamine secretion	1	1203.7×	0.002	CHRNB2
nervous system process	1	1203.7×	0.002	CHRNB2
smooth muscle contraction	1	802.5×	0.003	CHRNB2
synaptic transmission, cholinergic	1	802.5×	0.003	CHRNB2
regulation of dendrite morphogenesis	1	732.7×	0.003	CHRNB2
regulation of synapse assembly	1	702.2×	0.003	CHRNB2
acetylcholine receptor signaling pathway	1	624.1×	0.003	CHRNB2
response to cocaine	1	581.1×	0.004	CHRNB2
membrane depolarization	1	510.7×	0.004	CHRNB2
associative learning	1	481.5×	0.004	CHRNB2
B cell activation	1	455.5×	0.004	CHRNB2
response to nicotine	1	421.3×	0.004	CHRNB2
sensory perception of pain	1	374.5×	0.004	CHRNB2
positive regulation of B cell proliferation	1	343.9×	0.005	CHRNB2
visual learning	1	306.4×	0.005	CHRNB2
cognition	1	285.6×	0.005	CHRNB2
learning	1	280.9×	0.005	CHRNB2
social behavior	1	271.8×	0.005	CHRNB2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
CHRNB2	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNB2	26	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARENICLINE	4	CHRNB2
MECAMYLAMINE	4	CHRNB2
GRANISETRON	4	CHRNB2
NICOTINE	4	CHRNB2
ONDANSETRON	4	CHRNB2
TROPISETRON	4	CHRNB2
ACETYLCHOLINE	4	CHRNB2
BUPROPION	4	CHRNB2
CARBAMOYLCHOLINE	4	CHRNB2
DEXMECAMYLAMINE	3	CHRNB2
CYTISINICLINE	3	CHRNB2
ALTINICLINE	2	CHRNB2
RADAFAXINE	2	CHRNB2
LOBELINE	2	CHRNB2
STILONIUM IODIDE	2	CHRNB2
BRADANICLINE	2	CHRNB2
POZANICLINE	2	CHRNB2
RIVANICLINE	2	CHRNB2
GTS-21	2	CHRNB2
ISPRONICLINE	2	CHRNB2
AZD0328	2	CHRNB2
AZD1446	2	CHRNB2
SOFINICLINE	2	CHRNB2
TEBANICLINE	2	CHRNB2
TC-2216	1	CHRNB2
NORNICOTINE	1	CHRNB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRNB2	696	Binding:567, Functional:127, Toxicity:1, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CHRNB2	696

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

26 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)
VARENICLINE	4	CHRNB2
MECAMYLAMINE	4	CHRNB2
GRANISETRON	4	CHRNB2
NICOTINE	4	CHRNB2
ONDANSETRON	4	CHRNB2
TROPISETRON	4	CHRNB2
ACETYLCHOLINE	4	CHRNB2
BUPROPION	4	CHRNB2
CARBAMOYLCHOLINE	4	CHRNB2
DEXMECAMYLAMINE	3	CHRNB2
CYTISINICLINE	3	CHRNB2
ALTINICLINE	2	CHRNB2
RADAFAXINE	2	CHRNB2
LOBELINE	2	CHRNB2
STILONIUM IODIDE	2	CHRNB2
BRADANICLINE	2	CHRNB2
POZANICLINE	2	CHRNB2
RIVANICLINE	2	CHRNB2
GTS-21	2	CHRNB2
ISPRONICLINE	2	CHRNB2
AZD0328	2	CHRNB2
AZD1446	2	CHRNB2
SOFINICLINE	2	CHRNB2
TEBANICLINE	2	CHRNB2
TC-2216	1	CHRNB2
NORNICOTINE	1	CHRNB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHRNB2
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.