KCNQ2

Chr 20AD

potassium voltage-gated channel subfamily Q member 2

Also known as: BFNC, DEE7, EBN, EBN1, ENB1, HNSPC, KCNA11, KV7.2

NCBI Gene: 3785ENSG00000075043UniProt: O43526

The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 7MIM #613720
AD
MyokymiaMIM #121200
AD
Seizures, benign neonatal, 1MIM #121200
AD
UniProtSeizures, benign familial neonatal 1
2581
ClinVar variants
144
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— KCNQ2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
144 Pathogenic / Likely Pathogenic· 208 VUS of 2581 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 1.000
Z-score 5.55
OE 0.05 (0.02–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.04Z-score
OE missense 0.52 (0.47–0.57)
286 obs / 553.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.47–0.57)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 2 / 39.8Missense obs/exp: 286 / 553.6Syn Z: -1.18

ClinVar Variant Classifications

2581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic50
VUS208
Likely Benign137
Benign3
Conflicting4
94
Pathogenic
50
Likely Pathogenic
208
VUS
137
Likely Benign
3
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
39
17
38
0
94
Likely Pathogenic
9
33
8
0
50
VUS
2
164
36
6
208
Likely Benign
0
1
57
79
137
Benign
0
0
3
0
3
Conflicting
—4
Total5021514285496

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KCNQ2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

KCNQ2-related epileptic encephalopathy

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

KCNQ2-related benign neonatal epilepsy

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 7

MIM #613720

Molecular basis of disorder known

Autosomal dominant

Myokymia

MIM #121200

Molecular basis of disorder known

Autosomal dominant

Seizures, benign neonatal, 1

MIM #121200

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.
Lindy AS et al.·Epilepsia
2018Cohort
Targeting Kv7 Potassium Channels for Epilepsy.
Perucca E et al.·CNS Drugs
2025Review
New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing.
Bruno LP et al.·Int J Mol Sci
2021Clinical trial
The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures.
Burgess R et al.·Ann Neurol
2019
Genetic determinants of global developmental delay and intellectual disability in Ukrainian children.
Shchubelka K et al.·J Neurodev Disord
2024
Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort.
Symonds JD et al.·Brain
2019Cohort
The epilepsy-autism phenotype associated with developmental and epileptic encephalopathies: New mechanism-based therapeutic options.
Specchio N et al.·Epilepsia
2025Review
Unraveling the genetic basis of epilepsy: Recent advances and implications for diagnosis and treatment.
Dwivedi R et al.·Brain Res
2024Review
Rates of Status Epilepticus and Sudden Unexplained Death in Epilepsy in People With Genetic Developmental and Epileptic Encephalopathies.
Donnan AM et al.·Neurology
2023
Ligand activation mechanisms of human KCNQ2 channel.
Ma D et al.·Nat Commun
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Coupling of functionality to trafficking of KCNQ2/3 potassium channels at the axon initial segment.
Yoshioka D et al.·Proc Natl Acad Sci U S A
2026Functional
Molecular dynamics of the pathogenic KCNQ2 variant G256W reveals mechanisms of channel dysfunction in epileptic encephalopathy.
Thompson EC et al.·J Biomol Struct Dyn
2026Functional
KCNQ2 downregulation in left stellate ganglion neurons exacerbates malignant ventricular arrhythmias after myocardial infarction.
Zhou MM et al.·J Mol Cell Cardiol
2026
Integrated genotype-phenotype function analysis reveals distinct pathogenic mechanisms for cognitive impairment in KCNQ2-related disorders.
Xiong J et al.·Epilepsia
2026Functional
Mislocalization of KCNQ2 Channels as a Pathogenic Mechanism in KCNQ2 Developmental and Epileptic Encephalopathy.
Springer K et al.·J Neurosci
2026Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Epileptic Encephalopathy

Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy

RECRUITING
NCT04802135Assistance Publique Hopitaux De MarseilleStarted 2021-03-06
Survey
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet

External Resources

Links to major genomics databases and tools