KCNQ2

potassium voltage-gated channel subfamily Q member 2, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 20:63400208-63472677

Previous symbols: [ "EBN", "EBN1" ]

Links

ENSG00000075043 ∙ NCBI:3785 ∙ OMIM:602235 ∙ HGNC:6296 ∙ Uniprot:O43526 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• seizures, benign familial neonatal, 1 (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 7 (Definitive), mode of inheritance: AD
• benign neonatal seizures (Supportive), mode of inheritance: AD
• benign familial infantile epilepsy (Supportive), mode of inheritance: AD
• benign familial neonatal-infantile seizures (Supportive), mode of inheritance: AD
• malignant migrating partial seizures of infancy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 7 (Supportive), mode of inheritance: AD
• seizures, benign familial neonatal, 2 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 7 (Strong), mode of inheritance: AD
• neonatal-onset developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
• neonatal encephalopathy with non-epileptic myoclonus (Definitive), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epileptic encephalopathy, early infantile, 7	AD	Neurologic	Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology	Neurologic	7980108; 9430594; 9425895; 11572947; 12742592; 15249611; 16235065; 16966552; 17675531; 17872363; 19822871; 22169383; 22275249; 22884718; 22926866; 28331464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNQ2 gene.

• Early infantile epileptic encephalopathy with suppression bursts (236 variants)
• not provided (109 variants)
• Developmental and epileptic encephalopathy, 7 (56 variants)
• Seizures, benign familial neonatal, 1 (54 variants)
• Complex neurodevelopmental disorder (23 variants)
• KCNQ2-related disorder (12 variants)
• Inborn genetic diseases (12 variants)
• Seizures, benign familial neonatal, 1;Developmental and epileptic encephalopathy, 7 (8 variants)
• Seizure (8 variants)
• Epileptic encephalopathy (4 variants)
• Seizures, benign familial neonatal, 1, and/or myokymia (2 variants)
• Seizures, benign familial neonatal, 2 (2 variants)
• Autosomal recessive congenital ichthyosis 10 (1 variants)
• Neonatal encephalopathy (1 variants)
• Seizure;Generalized hypotonia (1 variants)
• See cases (1 variants)
• Developmental and epileptic encephalopathy, 7;Seizures, benign familial neonatal, 1 (1 variants)
• Intellectual disability (1 variants)
• Febrile seizures, familial, 8 (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• Severe intellectual deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNQ2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	11	332	14	358
missense	119	188	458	15	4	784
nonsense	49	5	1			55
start loss	3	2				5
frameshift	140	23	1			164
inframe indel	5	5	14			24
splice donor/acceptor (+/-2bp)	18	32	4			54
splice region	2	2	37	45	3	89
non coding	1	1	3	196	102	303
Total	335	257	492	543	120

Highest pathogenic variant AF is 0.00000657

Variants in KCNQ2

This is a list of pathogenic ClinVar variants found in the KCNQ2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-63400679-T-C			Likely benign (Nov 01, 2022)
20-63400682-C-A		not specified	Benign (Jul 15, 2024)
20-63400695-C-T			Likely benign (May 01, 2023)
20-63400714-G-A			Likely benign (Jan 01, 2023)
20-63400729-G-A			Benign (Oct 01, 2022)
20-63400740-G-C			Likely benign (Jun 01, 2023)
20-63406349-G-A			Benign (Jun 19, 2018)
20-63406396-G-A			Benign (Jun 14, 2018)
20-63406615-G-A			Benign (May 20, 2021)
20-63406621-G-T			Benign (Jun 17, 2021)
20-63406638-G-A			Likely benign (Jul 15, 2020)
20-63406640-C-T		not specified • Inborn genetic diseases • KCNQ2-related disorder	Benign/Likely benign (Nov 01, 2024)
20-63406641-G-A			Likely benign (Jan 15, 2020)
20-63406645-C-T			Likely benign (Dec 01, 2022)
20-63406647-C-G		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Mar 02, 2023)
20-63406650-C-A		not specified • Early infantile epileptic encephalopathy with suppression bursts • Developmental and epileptic encephalopathy, 7 • Seizures, benign familial neonatal, 1	Benign/Likely benign (Jan 31, 2024)
20-63406651-C-T		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
20-63406652-T-C		Early infantile epileptic encephalopathy with suppression bursts • Inborn genetic diseases	Uncertain significance (Dec 01, 2023)
20-63406653-G-GGGCCC		Seizures, benign familial neonatal, 1	Pathogenic (Mar 31, 2016)
20-63406655-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Aug 25, 2022)
20-63406655-GC-G		Early infantile epileptic encephalopathy with suppression bursts	Pathogenic (Nov 19, 2022)
20-63406656-C-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Sep 27, 2022)
20-63406658-C-T		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Nov 12, 2023)
20-63406659-G-A		not specified • Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 23, 2023)
20-63406659-G-GGCCCA		Seizures, benign familial neonatal, 1 • Inborn genetic diseases • Early infantile epileptic encephalopathy with suppression bursts	Pathogenic/Likely pathogenic (Feb 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNQ2	protein_coding	protein_coding	ENST00000359125	17	66452

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000167	125740	0	4	125744	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.04	286	554	0.517	0.0000396	5568
Missense in Polyphen		81	238.29	0.33993		2238
Synonymous	-1.18	285	261	1.09	0.0000213	1793
Loss of Function	5.55	2	39.8	0.0503	0.00000197	445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000639	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000268	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine (PubMed:9836639, PubMed:11572947, PubMed:14534157, PubMed:12742592, PubMed:17872363). As the native M-channel, the potassium channel composed of KCNQ2 and KCNQ3 is also suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10684873). {ECO:0000269|PubMed:10684873, ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:17872363, ECO:0000269|PubMed:25740509, ECO:0000269|PubMed:9836639}.
• Disease: DISEASE: Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia. {ECO:0000269|PubMed:11175290, ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:9425895}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 7 (EIEE7) [MIM:613720]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. {ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:25740509, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cholinergic synapse - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Splicing factor NOVA regulated synaptic proteins;Developmental Biology;ion channels and their functional role in vascular endothelium;Neuronal System;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.00282
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.86

Haploinsufficiency Scores

• pHI: 0.491
• hipred: Y
• hipred_score: 0.875
• ghis: 0.647

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnq2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;nervous system development;regulation of ion transmembrane transport;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;integral component of membrane;node of Ranvier;axon initial segment
• Molecular function: voltage-gated potassium channel activity;delayed rectifier potassium channel activity;protein binding;calmodulin binding;ankyrin binding