KCNE3

potassium voltage-gated channel subfamily E regulatory subunit 3, the group of Potassium voltage-gated channel regulatory subunits

Basic information

Region (hg38): 11:74454841-74467729

Links

ENSG00000175538 ∙ NCBI:10008 ∙ OMIM:604433 ∙ HGNC:6243 ∙ Uniprot:Q9Y6H6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome 6 (Limited), mode of inheritance: Unknown
• Brugada syndrome 6 (Disputed Evidence), mode of inheritance: AD
• Brugada syndrome 6 (Disputed Evidence), mode of inheritance: Unknown
• Brugada syndrome 6 (Limited), mode of inheritance: AD
• Brugada syndrome (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brugada syndrome 6	AD	Cardiovascular; Pharmacogenomic	Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	Cardiovascular	12414843; 14504341; 15037716; 15212652; 19122847; 19306396; 19606473; 20301690; 22397033; 22987075

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNE3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNE3 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				13	2	15
missense			47	1		48
nonsense			1			1
start loss			1			1
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			8	8	10	26
Total	0	0	61	22	12

Variants in KCNE3

This is a list of pathogenic ClinVar variants found in the KCNE3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-74455736-G-GT		Brugada syndrome	Likely benign (Jun 14, 2016)
11-74455736-G-GTT		Brugada syndrome	Likely benign (Jun 14, 2016)
11-74456155-AATATAT-A		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456155-A-AATATATATAT		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456155-A-AATATATATATATAT		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456328-T-TAAA		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456329-C-CAAA		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456329-C-CAAAA		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74456341-AAG-A		Brugada syndrome	Likely benign (Jun 14, 2016)
11-74457172-T-C			Benign (Jun 19, 2018)
11-74457214-C-T		Brugada syndrome	Uncertain significance (Jun 14, 2016)
11-74457235-G-A		not specified	Benign (Jan 08, 2024)
11-74457249-G-A			Likely benign (Jun 10, 2021)
11-74457254-A-G		Brugada syndrome 6	Uncertain significance (Oct 27, 2017)
11-74457260-T-C		Brugada syndrome 6 • Cardiovascular phenotype • Long QT syndrome	Uncertain significance (Mar 11, 2024)
11-74457266-C-T		Cardiovascular phenotype	Uncertain significance (Jun 17, 2024)
11-74457268-C-T		Brugada syndrome 6 • Brugada syndrome • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Mar 01, 2024)
11-74457269-G-A		Cardiovascular phenotype • Brugada syndrome 6	Uncertain significance (Jun 14, 2022)
11-74457277-A-C		Cardiovascular phenotype	Uncertain significance (Feb 27, 2024)
11-74457282-C-T		Cardiovascular phenotype	Likely benign (Aug 16, 2022)
11-74457284-CAT-C		Brugada syndrome 6	Uncertain significance (Nov 27, 2023)
11-74457285-A-G		Brugada syndrome 6 • Cardiovascular phenotype	Likely benign (Dec 14, 2022)
11-74457285-A-T		Brugada syndrome 6	Uncertain significance (Jul 05, 2022)
11-74457286-T-C		Cardiovascular phenotype	Uncertain significance (Dec 11, 2023)
11-74457287-G-A		Cardiovascular phenotype	Uncertain significance (Feb 16, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNE3	protein_coding	protein_coding	ENST00000310128	1	12889

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.468	0.450	125695	0	8	125703	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.238	62	67.5	0.918	0.00000422	668
Missense in Polyphen		19	23.551	0.80676		256
Synonymous	0.548	21	24.4	0.859	0.00000123	218
Loss of Function	1.19	0	1.65	0.00	6.88e-8	23

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000431	0.000431
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:12954870). Associated with KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated potassium channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells. Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship. {ECO:0000250|UniProtKB:Q9JJV7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:12954870}.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Antiarrhythmic Pathway, Pharmacodynamics;TYROBP Causal Network;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.219
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.310
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.821

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kcne3
• Phenotype: hearing/vestibular/ear 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); digestive/alimentary phenotype; immune system phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of ventricular cardiac muscle cell membrane repolarization;ventricular cardiac muscle cell action potential;membrane repolarization during action potential;regulation of heart rate by cardiac conduction;potassium ion export across plasma membrane;membrane repolarization during ventricular cardiac muscle cell action potential;positive regulation of voltage-gated calcium channel activity;negative regulation of delayed rectifier potassium channel activity;negative regulation of potassium ion export across plasma membrane;negative regulation of voltage-gated potassium channel activity;negative regulation of membrane repolarization during ventricular cardiac muscle cell action potential
• Cellular component: cytoplasm;plasma membrane;voltage-gated potassium channel complex;dendrite;vesicle;neuronal cell body membrane;perikaryon;membrane raft
• Molecular function: delayed rectifier potassium channel activity;protein binding;potassium channel regulator activity;ion channel binding;voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization