KCNN3 Gene

HGNC Family	Ion channels
Name	potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 3
Description	Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The KCNN3 gene encodes the small‐conductance Ca<sup>2+</sup>–activated K<sup>+</sup> channel 3 (SK3), which plays diverse roles in regulating cell excitability and membrane repolarization across several tissues. In the heart, genetic variants within KCNN3 have been linked to atrial fibrillation by affecting atrial repolarization processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the urinary bladder, SK3 channels expressed in smooth muscle cells contribute to the regulation of contractility and non‐voiding contractions, indicating their importance in controlling bladder function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Within the central nervous system, SK3 exhibits a distinct distribution pattern – being predominantly present in phylogenetically older brain regions such as the basal ganglia and brainstem – where it helps modulate neuronal excitability. Furthermore, increased SK3 expression in the hippocampus has been associated with impaired synaptic plasticity and deficits in learning and memory."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, SK3 functions as a key component in the regulation of cell migration. It achieves this through the formation of a lipid raft–associated complex with calcium channels (such as Orai1), which facilitates constitutive Ca<sup>2+</sup> entry and, consequently, supports migratory behavior and metastatic dissemination – notably in bone metastases and colon cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KCNN3/SK3 channels are multifunctional proteins that regulate electrical activity and cellular excitability in the heart, vasculature, brain, and cancer cells. Their activity is integral not only to physiological repolarization and signal modulation but also to pathophysiological processes such as arrhythmogenesis and tumor cell migration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Patrick T Ellinor, Kathryn L Lunetta, Nicole L Glazer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants in KCNN3 are associated with lone atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.537"}], "href": "https://doi.org/10.1038/ng.537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20173747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20173747"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gerald M Herrera, Maria J Pozo, Peter Zvara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urinary bladder instability induced by selective suppression of the murine small conductance calcium-activated potassium (SK3) channel."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2003.045914"}], "href": "https://doi.org/10.1113/jphysiol.2003.045914"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12813145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12813145"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Claudia A Sailer, Walter A Kaufmann, Josef Marksteiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Neurosci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcn.2004.03.002"}], "href": "https://doi.org/10.1016/j.mcn.2004.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15234350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15234350"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas Blank, Ingrid Nijholt, Min-Jeong Kye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small-conductance, Ca2+-activated K+ channel SK3 generates age-related memory and LTP deficits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1101"}], "href": "https://doi.org/10.1038/nn1101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12883553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12883553"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aurélie Chantôme, Marie Potier-Cartereau, Lucie Clarysse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pivotal role of the lipid Raft SK3-Orai1 complex in human cancer cell migration and bone metastases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-4572"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-4572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23774210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23774210"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Maxime Guéguinou, Thomas Harnois, David Crottes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.8786"}], "href": "https://doi.org/10.18632/oncotarget.8786"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27102434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27102434"}]}]}]}
Synonyms	SK3, SKCA3, KCA2.3, HSK3
Proteins	KCNN3_HUMAN
NCBI Gene ID	3782
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNN3 has 6,333 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 123 datasets.

Click the + buttons to view associations for KCNN3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNN3 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 KCNN3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNN3 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 KCNN3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNN3 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 KCNN3 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 KCNN3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNN3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNN3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNN3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KCNN3 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 KCNN3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 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 KCNN3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNN3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNN3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNN3 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 KCNN3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNN3 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 KCNN3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with KCNN3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.