KCNQ3

potassium voltage-gated channel subfamily Q member 3, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 8:132120858-132481095

Previous symbols: [ "EBN2" ]

Links

ENSG00000184156 ∙ NCBI:3786 ∙ OMIM:602232 ∙ HGNC:6297 ∙ Uniprot:O43525 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• seizures, benign familial neonatal, 2 (Moderate), mode of inheritance: AD
• benign neonatal seizures (Supportive), mode of inheritance: AD
• benign familial infantile epilepsy (Supportive), mode of inheritance: AD
• seizures, benign familial neonatal, 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Seizures, benign familial neonatal, 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	1859177; 8102508; 9425900; 20437616; 22612257

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNQ3 gene.

• Benign neonatal seizures (809 variants)
• not provided (331 variants)
• Seizures, benign familial neonatal, 2 (288 variants)
• Inborn genetic diseases (98 variants)
• Benign Neonatal Epilepsy (94 variants)
• not specified (93 variants)
• KCNQ3-related condition (6 variants)
• Intellectual disability (6 variants)
• Childhood epilepsy with centrotemporal spikes (3 variants)
• Seizure (2 variants)
• Severe neurodevelopmental delay (1 variants)
• Intellectual disability;Seizure (1 variants)
• Developmental disorder (1 variants)
• See cases (1 variants)
• Autism spectrum disorder (1 variants)
• Lennox-Gastaut syndrome;Intellectual disability;Benign neonatal seizures (1 variants)
• Autistic behavior (1 variants)
• Seizures, benign familial infantile, 5 (1 variants)
• Intellectual disability, severe (1 variants)
• Early Infantile Epileptic Encephalopathy, Autosomal Dominant;Early Infantile Epileptic Encephalopathy, Autosomal Recessive;Benign neonatal seizures (1 variants)
• KCNQ3-related developmental disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNQ3 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			11	209	6	226
missense	6	19	376	18	1	420
nonsense	6		7			13
start loss			1			1
frameshift	8		12			20
inframe indel			21			21
splice donor/acceptor (+/-2bp)		2				2
splice region		1	19	29		49
non coding			104	135	122	361
Total	20	21	532	362	129

Highest pathogenic variant AF is 0.00000658

Variants in KCNQ3

This is a list of pathogenic ClinVar variants found in the KCNQ3 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-132121114-C-T		Seizures, benign familial neonatal, 2 • Benign Neonatal Epilepsy	Benign (Jan 13, 2018)
8-132121160-C-T		Seizures, benign familial neonatal, 2	Uncertain significance (Jan 12, 2018)
8-132121281-G-GA		Benign neonatal seizures • Benign Neonatal Epilepsy	Uncertain significance (Jun 14, 2016)
8-132121339-C-G		Seizures, benign familial neonatal, 2	Uncertain significance (Jan 12, 2018)
8-132121540-A-T		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign/Likely benign (Jan 13, 2018)
8-132121573-T-C		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign/Likely benign (Jan 12, 2018)
8-132121750-A-C		Benign Neonatal Epilepsy • Seizures, benign familial neonatal, 2	Uncertain significance (Jan 12, 2018)
8-132121756-G-A		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign (Jan 13, 2018)
8-132121758-G-C		Benign neonatal seizures • Seizures, benign familial neonatal, 2	Benign/Likely benign (Jan 13, 2018)
8-132121798-G-T		Seizures, benign familial neonatal, 2 • Benign Neonatal Epilepsy	Benign/Likely benign (Jan 13, 2018)
8-132121801-C-T		Seizures, benign familial neonatal, 2	Benign (Mar 06, 2018)
8-132121849-C-G		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign/Likely benign (Jan 13, 2018)
8-132121854-C-A		Seizures, benign familial neonatal, 2	Uncertain significance (Jan 13, 2018)
8-132121891-A-C		Benign neonatal seizures • Seizures, benign familial neonatal, 2	Benign (Jan 13, 2018)
8-132121931-T-C		Seizures, benign familial neonatal, 2 • Benign Neonatal Epilepsy	Conflicting classifications of pathogenicity (Jan 12, 2018)
8-132122019-G-C		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Uncertain significance (Jan 13, 2018)
8-132122041-G-A		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign (Jan 13, 2018)
8-132122048-C-T		Seizures, benign familial neonatal, 2 • Benign Neonatal Epilepsy	Benign/Likely benign (Jan 12, 2018)
8-132122058-C-T		Seizures, benign familial neonatal, 2	Uncertain significance (Jan 13, 2018)
8-132122102-G-C		Seizures, benign familial neonatal, 2	Uncertain significance (Jan 12, 2018)
8-132122119-T-C		Benign neonatal seizures • Seizures, benign familial neonatal, 2	Benign (Jan 13, 2018)
8-132122131-C-T		Benign neonatal seizures • Seizures, benign familial neonatal, 2	Benign (Jan 13, 2018)
8-132122132-G-A		Seizures, benign familial neonatal, 2	Benign (Jan 12, 2018)
8-132122143-G-A		Benign neonatal seizures • Seizures, benign familial neonatal, 2	Benign (Jan 13, 2018)
8-132122167-A-C		Seizures, benign familial neonatal, 2 • Benign neonatal seizures	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNQ3	protein_coding	protein_coding	ENST00000388996	15	360093

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.801	0.199	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	350	477	0.734	0.0000291	5604
Missense in Polyphen		109	209.28	0.52083		2433
Synonymous	0.409	193	200	0.963	0.0000129	1796
Loss of Function	4.74	8	40.5	0.197	0.00000251	451

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000272	0.0000264
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with KCNQ2 or KCNQ5 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. {ECO:0000269|PubMed:11159685, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:16319223, ECO:0000269|PubMed:9872318}.
• Disease: DISEASE: Seizures, benign familial neonatal 2 (BFNS2) [MIM:121201]: 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. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. {ECO:0000269|PubMed:10852552, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:9425900, ECO:0000269|PubMed:9872318}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in KCNQ3 may be involved in epileptic disorders. These are characterized by paroxysmal transient disturbances of the electrical activity of the brain that may be manifested as episodic impairment or loss of consciousness, abnormal motor phenomena, psychic or sensory disturbances, or perturbation of the autonomic nervous system. {ECO:0000269|PubMed:22612257}.
• Pathway: Cholinergic synapse - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;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: 0.109

Intolerance Scores

• loftool: 0.0830
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.82

Haploinsufficiency Scores

• pHI: 0.771
• hipred: Y
• hipred_score: 0.850
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.806

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcnq3
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Zebrafish Information Network

• Gene name: kcnq3
• Affected structure: transmission of nerve impulse
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: chemical synaptic transmission;regulation of ion transmembrane transport;membrane hyperpolarization;potassium ion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;voltage-gated potassium channel complex;cell surface;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