KCNA3 Gene

HGNC Family	Ion channels
Name	potassium channel, voltage gated shaker related subfamily A, member 3
Description	Potassium 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, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNA3, which encodes the voltage‐gated potassium channel Kv1.3, plays a multifaceted role in regulating cellular excitability across several tissues. In T lymphocytes, Kv1.3 is a critical determinant of effector memory cell activation and proliferation by modulating Ca²⁺ signaling and contributing to immunological synapse formation. These functions are supported by observations that autoreactive, antigen‐specific T cells express high levels of Kv1.3 and that its blockade suppresses calcium oscillations, cytokine production, and proliferation—findings that underpin its potential as a therapeutic target in autoimmune disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its plasma membrane localization, Kv1.3 is functionally expressed in the inner mitochondrial membrane of lymphocytes, where it governs apoptotic processes by interacting with pro‐apoptotic proteins such as Bax. Its inhibition in this compartment impairs cytochrome c release and renders cells resistant to apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Kv1.3 also contributes to peripheral metabolic regulation. In adipose tissue and skeletal muscle, channel inhibition improves insulin sensitivity by promoting GLUT4 translocation, which has been linked to improved glucose uptake and favorable metabolic profiles in obesity and type II diabetes models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In innate immune cells such as macrophages, Kv1.3 forms heterotetramers with Kv1.5, and this molecular partnership modulates macrophage activation and proliferation, thereby influencing inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, Kv1.3 is implicated in neuronal function; in the olfactory system, for example, its deletion leads to enhanced odor detection and altered neuronal coding, indicating a broader role in regulating sensory perception."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the diverse roles of KCNA3/Kv1.3 in the regulation of T cell activity, apoptosis, metabolic homeostasis, and inflammatory as well as neuronal functions underscore its importance as a central modulator of cellular excitability. Its selective expression and pharmacological tractability render Kv1.3 an attractive therapeutic target for treating autoimmune, metabolic, and possibly neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christine Beeton, Heike Wulff, Nathan E Standifer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0605136103"}], "href": "https://doi.org/10.1073/pnas.0605136103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17088564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17088564"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "G Panyi, G Vámosi, Z Bacsó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0307421100"}], "href": "https://doi.org/10.1073/pnas.0307421100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14745040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14745040"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lina Hu, Michael Pennington, Qiong Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the functional properties of the voltage-gated potassium channel Kv1.3 in human CD4+ T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.179.7.4563"}], "href": "https://doi.org/10.4049/jimmunol.179.7.4563"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17878353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17878353"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Horea Rus, Carlos A Pardo, Lina Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0501770102"}], "href": "https://doi.org/10.1073/pnas.0501770102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16043714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16043714"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yunzhao R Ren, Fan Pan, Suhel Parvez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004009"}], "href": "https://doi.org/10.1371/journal.pone.0004009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19104661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19104661"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ildikò Szabò, Jurgen Bock, Andreas Jekle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel potassium channel in lymphocyte mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413548200"}], "href": "https://doi.org/10.1074/jbc.M413548200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15632141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15632141"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ildikò Szabó, Jürgen Bock, Heike Grassmé, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0804236105"}], "href": "https://doi.org/10.1073/pnas.0804236105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18818304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18818304"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Erich Gulbins, Nicola Sassi, Heike Grassmè, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Kv1.3 mitochondrial potassium channel in apoptotic signalling in lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbabio.2010.01.018"}], "href": "https://doi.org/10.1016/j.bbabio.2010.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20114030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20114030"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jianchao Xu, Peili Wang, Yanyan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0308450100"}], "href": "https://doi.org/10.1073/pnas.0308450100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14981264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14981264"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rubén Vicente, Artur Escalada, Mireia Coma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential voltage-dependent K+ channel responses during proliferation and activation in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304388200"}], "href": "https://doi.org/10.1074/jbc.M304388200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12923194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12923194"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Rubén Vicente, Artur Escalada, Nuria Villalonga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+ channel in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M605617200"}], "href": "https://doi.org/10.1074/jbc.M605617200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17038323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17038323"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Alessandra Cambi, Frank de Lange, Noortje M van Maarseveen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200306112"}], "href": "https://doi.org/10.1083/jcb.200306112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14709546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14709546"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Anne R Gocke, Lori A Lebson, Inna V Grishkan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kv1.3 deletion biases T cells toward an immunoregulatory phenotype and renders mice resistant to autoimmune encephalomyelitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1103095"}], "href": "https://doi.org/10.4049/jimmunol.1103095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22581856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22581856"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Mireia Pérez-Verdaguer, Jesusa Capera, Clara Serrano-Novillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The voltage-gated potassium channel Kv1.3 is a promising multitherapeutic target against human pathologies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Expert Opin Ther Targets (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1517/14728222.2016.1112792"}], "href": "https://doi.org/10.1517/14728222.2016.1112792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26634786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26634786"}]}]}]}
Synonyms	MK3, HLK3, HUKIII, KV1.3, HGK5, HPCN3
Proteins	KCNA3_HUMAN
NCBI Gene ID	3738
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNA3 has 7,246 functional associations with biological entities spanning 8 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) extracted from 113 datasets.

Click the + buttons to view associations for KCNA3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNA3 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 KCNA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNA3 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 KCNA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNA3 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 KCNA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KCNA3 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 KCNA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNA3 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 KCNA3 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 KCNA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNA3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNA3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNA3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 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 KCNA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNA3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNA3 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 KCNA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNA3 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 KCNA3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with KCNA3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KCNA3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.