Seizures, benign familial neonatal, 2

Summary

Seizures, benign familial neonatal, 2 (MONDO:0007366) is a disease caused by variants in KCNQ2 and KCNQ3, with 2 cohort genes.

At a glance

• Causal genes: KCNQ2 (GenCC Strong), KCNQ3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 315

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	seizures, benign familial neonatal, 2
Mondo ID	MONDO:0007366
OMIM	121201
UMLS	C1852581
MedGen	377707
GARD	0015054
Is cancer (heuristic)	no

Also known as: benign neonatal seizures caused by mutation in KCNQ3 · BFNS2 · KCNQ3 benign neonatal seizures · seizures, benign familial neonatal, 2 · seizures, benign familial neonatal, type 2 · seizures, benign neonatal, 2

Data availability: 315 ClinVar variants · 4 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 › epilepsy syndrome › neonatal epilepsy syndrome › benign neonatal seizures › seizures, benign familial neonatal, 2

Related subtypes (3): seizures, benign familial neonatal, 1, seizures, benign familial neonatal, autosomal recessive, seizures, benign familial neonatal, 3

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

315 retrieved; paginated sample, class counts are floors:

139 uncertain significance, 78 benign, 38 conflicting classifications of pathogenicity, 29 benign/likely benign, 8 likely pathogenic, 7 pathogenic, 7 likely benign, 6 pathogenic/likely pathogenic, 3 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
7388	NM_172107.4(KCNQ2):c.1662G>T (p.Lys554Asn)	KCNQ2	Pathogenic	criteria provided, single submitter
7389	NM_172107.4(KCNQ2):c.740C>G (p.Ser247Trp)	KCNQ2	Pathogenic	criteria provided, multiple submitters, no conflicts
1334436	NM_004519.4(KCNQ3):c.989G>T (p.Arg330Leu)	KCNQ3	Pathogenic	criteria provided, single submitter
205963	NM_004519.4(KCNQ3):c.688C>T (p.Arg230Cys)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21415	NM_004519.4(KCNQ3):c.925T>C (p.Trp309Arg)	KCNQ3	Pathogenic	no assertion criteria provided
21417	NM_004519.4(KCNQ3):c.988C>T (p.Arg330Cys)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424397	NM_004519.4(KCNQ3):c.689G>A (p.Arg230His)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
433110	NM_004519.4(KCNQ3):c.1142C>T (p.Ala381Val)	KCNQ3	Pathogenic	no assertion criteria provided
656938	NM_004519.4(KCNQ3):c.1090C>T (p.Arg364Cys)	KCNQ3	Pathogenic	criteria provided, single submitter
661030	NM_004519.4(KCNQ3):c.950T>C (p.Ile317Thr)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7392	NM_004519.4(KCNQ3):c.929G>T (p.Gly310Val)	KCNQ3	Pathogenic	no assertion criteria provided
852086	NM_004519.4(KCNQ3):c.989G>A (p.Arg330His)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
934997	NM_004519.4(KCNQ3):c.1091G>A (p.Arg364His)	KCNQ3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1319941	NM_004519.4(KCNQ3):c.1066G>A (p.Ala356Thr)	KCNQ3	Likely pathogenic	no assertion criteria provided
1334438	NM_004519.4(KCNQ3):c.835G>T (p.Val279Phe)	KCNQ3	Likely pathogenic	criteria provided, single submitter
2578394	NM_004519.4(KCNQ3):c.1120C>G (p.Pro374Ala)	KCNQ3	Likely pathogenic	criteria provided, single submitter
4056522	NM_004519.4(KCNQ3):c.778-2A>G	KCNQ3	Likely pathogenic	criteria provided, single submitter
420680	NM_004519.4(KCNQ3):c.923G>C (p.Trp308Ser)	KCNQ3	Likely pathogenic	criteria provided, single submitter
4538235	NM_004519.4(KCNQ3):c.928G>T (p.Gly310Cys)	KCNQ3	Likely pathogenic	criteria provided, single submitter
495233	NM_004519.4(KCNQ3):c.899T>C (p.Phe300Ser)	KCNQ3	Likely pathogenic	criteria provided, single submitter
998162	NM_004519.4(KCNQ3):c.104_105del (p.Ala35fs)	KCNQ3	Likely pathogenic	no assertion criteria provided
1036952	NM_004519.4(KCNQ3):c.508G>A (p.Glu170Lys)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1686662	NM_004519.4(KCNQ3):c.977C>T (p.Thr326Met)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193878	NM_004519.4(KCNQ3):c.1564G>A (p.Val522Ile)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194513	NM_004519.4(KCNQ3):c.1994C>T (p.Ser665Leu)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205961	NM_004519.4(KCNQ3):c.679C>T (p.Arg227Ter)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205969	NM_004519.4(KCNQ3):c.1216G>A (p.Val406Ile)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205970	NM_004519.4(KCNQ3):c.1226C>G (p.Pro409Arg)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205971	NM_004519.4(KCNQ3):c.1421C>T (p.Thr474Met)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
205972	NM_004519.4(KCNQ3):c.1507G>A (p.Gly503Arg)	KCNQ3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 9 · 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
KCNQ2	Definitive	Autosomal dominant	seizures, benign familial neonatal, 1	12
KCNQ3	Strong	Autosomal dominant	seizures, benign familial neonatal, 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNQ2	Orphanet:140927	Self-limited neonatal-infantile epilepsy
KCNQ2	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
KCNQ2	Orphanet:1949	Self-limited neonatal epilepsy
KCNQ2	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
KCNQ2	Orphanet:306	Self-limited infantile epilepsy
KCNQ2	Orphanet:439218	KCNQ2-related developmental and epileptic encephalopathy
KCNQ3	Orphanet:1949	Self-limited neonatal epilepsy
KCNQ3	Orphanet:306	Self-limited infantile epilepsy
KCNQ3	Orphanet:307	Juvenile 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
KCNQ2	HGNC:6296	ENSG00000075043	O43526	Potassium voltage-gated channel subfamily KQT member 2	gencc,clinvar
KCNQ3	HGNC:6297	ENSG00000184156	O43525	Potassium voltage-gated channel subfamily KQT member 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNQ2	Potassium voltage-gated channel subfamily KQT member 2	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.
KCNQ3	Potassium voltage-gated channel subfamily KQT member 3	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	2	111.5×	8e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNQ2	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ2, Ion_trans_dom
KCNQ3	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ3, Ion_trans_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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
Brodmann (1909) area 23	1
ganglionic eminence	1
lateral nuclear group of thalamus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNQ2	183	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
KCNQ3	180	broad	marker	ganglionic eminence, lateral nuclear group of thalamus, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNQ2	3,388
KCNQ3	2,665

Intra-cohort edges

A	B	Sources
KCNQ2	KCNQ3	biogrid_interaction, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNQ2	O43526	39
KCNQ3	O43525	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Interaction between L1 and Ankyrins	2	368.4×	6e-05	KCNQ2, KCNQ3
Voltage gated Potassium channels	2	243.0×	7e-05	KCNQ2, KCNQ3
Potassium Channels	2	134.3×	1e-04	KCNQ2, KCNQ3
L1CAM interactions	2	120.2×	1e-04	KCNQ2, KCNQ3
Axon guidance	2	45.1×	6e-04	KCNQ2, KCNQ3
Neuronal System	2	44.3×	6e-04	KCNQ2, KCNQ3
Nervous system development	2	42.9×	6e-04	KCNQ2, KCNQ3
Developmental Biology	2	14.5×	0.005	KCNQ2, KCNQ3

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
apoptosome assembly	1	8426.0×	0.001	KCNQ3
regulation of action potential firing threshold	1	8426.0×	0.001	KCNQ3
potassium ion transmembrane transport	2	135.9×	0.001	KCNQ2, KCNQ3
chemical synaptic transmission	2	77.3×	0.001	KCNQ2, KCNQ3
substantia propria of cornea development	1	4213.0×	0.001	KCNQ3
inhibitory chemical synaptic transmission	1	2808.7×	0.001	KCNQ3
action potential initiation	1	2808.7×	0.001	KCNQ3
psychomotor behavior	1	1685.2×	0.002	KCNQ3
mitochondrial depolarization	1	1203.7×	0.002	KCNQ3
membrane hyperpolarization	1	936.2×	0.003	KCNQ3
excitatory chemical synaptic transmission	1	648.1×	0.004	KCNQ3
neuron remodeling	1	601.9×	0.004	KCNQ3
nerve development	1	468.1×	0.004	KCNQ3
response to auditory stimulus	1	366.4×	0.005	KCNQ3
neuronal action potential	1	240.7×	0.007	KCNQ3
protein targeting	1	183.2×	0.009	KCNQ3
action potential	1	179.3×	0.009	KCNQ2
regulation of synaptic plasticity	1	129.6×	0.012	KCNQ3
cellular response to xenobiotic stimulus	1	120.4×	0.012	KCNQ3
cellular response to calcium ion	1	100.3×	0.013	KCNQ3
neuron apoptotic process	1	92.6×	0.014	KCNQ3
exocytosis	1	75.9×	0.016	KCNQ3
protein import into nucleus	1	72.0×	0.016	KCNQ3
sensory perception of sound	1	50.5×	0.022	KCNQ3
endocytosis	1	47.6×	0.023	KCNQ3
gene expression	1	39.9×	0.026	KCNQ3
nervous system development	1	23.0×	0.043	KCNQ2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
KCNQ2	FLUPIRTINE
KCNQ3	FLUPIRTINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNQ2	4	4
KCNQ3	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUPIRTINE	4	KCNQ2, KCNQ3
EZOGABINE	4	KCNQ2, KCNQ3
FLINDOKALNER	3	KCNQ2, KCNQ3
AZETUKALNER	3	KCNQ2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNQ2	145	Binding:136, Functional:7, ADMET:1, Toxicity:1
KCNQ3	97	Binding:91, Functional:4, ADMET:1, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KCNQ2	145

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

4 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)
FLUPIRTINE	4	KCNQ2, KCNQ3
EZOGABINE	4	KCNQ2, KCNQ3
FLINDOKALNER	3	KCNQ2, KCNQ3
AZETUKALNER	3	KCNQ2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	KCNQ2, KCNQ3
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.