KCNE3 Gene

HGNC Family	Potassium channel, voltage gated regulatory beta subunits
Name	potassium channel, voltage gated subfamily E regulatory beta subunit 3
Description	Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the kidney. A missense mutation in this gene is associated with hypokalemic periodic paralysis. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNE3 is an auxiliary subunit that plays a critical role in determining the gating and functional properties of its associated potassium‐conducting α subunits in both cardiac and epithelial tissues. When co‐assembled with KCNQ1, KCNE3 shifts the voltage sensor equilibrium toward its active state, thereby abolishing the intrinsic voltage dependence and producing constitutively active channels. This unique modulation has important physiological implications, as it underlies processes such as transepithelial ion transport in the intestine and airway, where the resulting KCNQ1–KCNE3 complexes are essential for Cl⁻ secretion and K⁺ recycling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and is summarized in broader reviews of KCNE regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the heart, KCNE3 can also interact with other pore‐forming α subunits. For instance, studies have demonstrated that when KCNE3 associates with components such as Kv4.3 or Kv11.1, mutations in KCNE3 (e.g., R99H or V17M) lead to a gain-of-function effect that increases current amplitudes. These alterations are implicated in arrhythmogenesis by enhancing the transient outward current (I(to)) or by accelerating repolarization, thereby predisposing mutation carriers to conditions like Brugada syndrome and atrial fibrillation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the biophysical level, KCNE3 exerts its modulatory effects by “unlocking” the voltage-sensing mechanism of KCNQ1. Detailed cysteine accessibility studies have shown that, in contrast to KCNE1, which stabilizes the S4 voltage sensor in its resting state, KCNE3 maintains the sensor in an accessible, active conformation even at hyperpolarized potentials."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In complementary experiments focused on cardiac electrophysiology, ectopic expression of KCNE3 has been shown to increase outward K⁺ currents and abbreviate action potential duration, thereby illustrating its potential to modify overall repolarization profiles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KCNE3 functions as a molecular switch that converts normally voltage-dependent channels into constitutively active forms. This property is critical for non-excitable epithelia where steady K⁺ conductance supports ion transport, yet it can also contribute to arrhythmogenic substrates in the heart when altered by mutation. The collective findings from genetic, electrophysiological, and molecular studies highlight the dual role of KCNE3 in both physiological ion transport and in the pathogenesis of cardiac arrhythmias."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Patricia Preston, Lena Wartosch, Dorothee Günzel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.047829"}], "href": "https://doi.org/10.1074/jbc.M109.047829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20051516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20051516"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Geoffrey W Abbott "}, {"type": "b", "children": [{"type": "t", "text": "KCNE1 and KCNE3: The yin and yang of voltage-gated K(+) channel regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.09.059"}], "href": "https://doi.org/10.1016/j.gene.2015.09.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26410412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26410412"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eva Delpón, Jonathan M Cordeiro, Lucía Núñez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Arrhythm Electrophysiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCEP.107.748103"}], "href": "https://doi.org/10.1161/CIRCEP.107.748103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19122847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19122847"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alicia Lundby, Lasse Steen Ravn, Jesper Hastrup Svendsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KCNE3 mutation V17M identified in a patient with lone atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000113746"}], "href": "https://doi.org/10.1159/000113746"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18209471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18209471"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Koichi Nakajo, Yoshihiro Kubo "}, {"type": "b", "children": [{"type": "t", "text": "KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1085/jgp.200709805"}], "href": "https://doi.org/10.1085/jgp.200709805"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17698596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17698596"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jessica M Rocheleau, William R Kobertz "}, {"type": "b", "children": [{"type": "t", "text": "KCNE peptides differently affect voltage sensor equilibrium and equilibration rates in KCNQ1 K+ channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1085/jgp.200709816"}], "href": "https://doi.org/10.1085/jgp.200709816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18079560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18079560"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Reza Mazhari, H Bradley Nuss, Antonis A Armoundas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI15062"}], "href": "https://doi.org/10.1172/JCI15062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11956246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11956246"}]}]}]}
Synonyms	MIRP2
Proteins	KCNE3_HUMAN
NCBI Gene ID	10008
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNE3 has 4,044 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for KCNE3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNE3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNE3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNE3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of KCNE3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KCNE3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of KCNE3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNE3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KCNE3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KCNE3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNE3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNE3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNE3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KCNE3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNE3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of KCNE3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with KCNE3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KCNE3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNE3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNE3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNE3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with KCNE3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNE3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNE3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNE3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNE3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KCNE3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNE3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving KCNE3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving KCNE3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCNE3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KCNE3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with KCNE3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with KCNE3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNE3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNE3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KCNE3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNE3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing KCNE3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with KCNE3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KCNE3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with KCNE3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.