KCND3 Gene

HGNC Family	Ion channels
Name	potassium channel, voltage gated Shal related subfamily D, member 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCND3 encodes the pore‐forming subunit Kv4.3, which is a key component of the transient outward potassium current (I<sub>to</sub>). In cardiac myocytes, I<sub>to</sub> critically contributes to the early repolarization phase of the action potential and thus helps determine the shape and duration of the cardiac action potential. Several studies have demonstrated that malfunction of KCND3‐encoded Kv4.3 impacts cardiac excitability and predisposes to arrhythmias. For example, gain‐of‐function mutations in KCND3 that increase I<sub>to</sub> density have been implicated in Brugada syndrome and early‐onset lone atrial fibrillation, where enhanced outward potassium current leads to abnormal repolarization and loss of the action potential dome (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, loss‐of‐function or mistrafficking of Kv4.3—as a consequence of mutations that impair proper membrane targeting—has been associated with neurodegenerative disorders such as spinocerebellar ataxia types 19/22, where impaired Kv4.3 function disrupts neuronal excitability (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, KCND3‐encoded channels are subject to complex regulation by a variety of accessory subunits—including KCNE3, KChIP2, and DPPX—that modulate channel trafficking, gating kinetics, and current amplitude. Notably, interactions between mutant forms of these accessory proteins and Kv4.3 can further alter I<sub>to</sub> properties and thus contribute to disease phenotypes (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KCND3 plays an essential role in both cardiac and neuronal excitability by encoding the Kv4.3 subunit responsible for generating I<sub>to</sub>. Its proper function is crucial for normal repolarization in the heart and for maintaining neuronal firing properties, while mutations that alter Kv4.3 function or its interaction with regulatory proteins can lead to arrhythmogenic syndromes or neurodegenerative disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "John R Giudicessi, Dan Ye, David J Tester, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Rhythm (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hrthm.2011.02.021"}], "href": "https://doi.org/10.1016/j.hrthm.2011.02.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21349352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21349352"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Morten Salling Olesen, Lena Refsgaard, Anders Gaarsdal Holst, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel KCND3 gain-of-function mutation associated with early-onset of persistent lone atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvt028"}], "href": "https://doi.org/10.1093/cvr/cvt028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23400760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23400760"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yi-Chung Lee, Alexandra Durr, Karen Majczenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in KCND3 cause spinocerebellar ataxia type 22."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.23701"}], "href": "https://doi.org/10.1002/ana.23701"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23280837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23280837"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anna Duarri, Justyna Jezierska, Michiel Fokkens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.23700"}], "href": "https://doi.org/10.1002/ana.23700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23280838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23280838"}]}, {"type": "r", "ref": 5, "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": 6, "children": [{"type": "t", "text": "Dan Hu, Hector Barajas-Martínez, Argelia Medeiros-Domingo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Rhythm (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hrthm.2011.12.006"}], "href": "https://doi.org/10.1016/j.hrthm.2011.12.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22155597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22155597"}]}]}]}
Synonyms	SCA19, KCND3S, KV4.3, SCA22, KCND3L, BRGDA9, KSHIVB
Proteins	KCND3_HUMAN
NCBI Gene ID	3752
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCND3 has 5,931 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 125 datasets.

Click the + buttons to view associations for KCND3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCND3 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 KCND3 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 KCND3 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 KCND3 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 KCND3 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 KCND3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KCND3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KCND3 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 KCND3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of KCND3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCND3 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 KCND3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KCND3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCND3 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 KCND3 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 KCND3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KCND3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KCND3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCND3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCND3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCND3 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 KCND3 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 KCND3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCND3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCND3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCND3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KCND3 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 KCND3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving KCND3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving KCND3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCND3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KCND3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KCND3 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 KCND3 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 KCND3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCND3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCND3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCND3 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 KCND3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCND3 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 KCND3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.