KCNN2 Gene

HGNC Family	Ion channels
Name	potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 2
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. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The KCNN2 gene encodes the SK2 channel, a small‐conductance Ca²⁺‐activated K⁺ channel that plays a pivotal role in modulating cellular excitability and synaptic integration. In central neurons, SK2 channels are highly enriched in dendritic spines where they attenuate excitatory postsynaptic potentials and shape long‐term plasticity—mechanisms that underlie learning and memory—as demonstrated in hippocampal CA1 pyramidal neurons and Purkinje cells (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, activity‐dependent regulation of KCNN2 expression has been observed in sensory neurons, suggesting that SK2 channels contribute to the adaptation and survival of these cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside the central nervous system, SK2 channels are also critical. For example, in cochlear hair cells, these channels shape the response to cholinergic efferent feedback and are essential for the long‐term maintenance of synaptic contacts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in cardiac myocytes, SK2 channels functionally interact with proteins such as junctophilin-2 that facilitate proper membrane localization and channel activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", indicating roles in the regulation of excitability in heart tissue as well as in other excitable cells.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Importantly, rare deleterious variants in KCNN2 have been identified in patients with neurodevelopmental disorders characterized by cerebellar ataxia, tremor, and cognitive deficits; these clinical observations recapitulate abnormalities seen in rodent models with spontaneous KCNN2 mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Additionally, genetic association studies have implicated KCNN2 in the pathogenesis of vascular complications such as coronary artery aneurysms in Kawasaki disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of KCNN2-encoded SK2 channels in governing excitability, synaptic plasticity, and cell survival across diverse tissues, and they highlight how disruptions in SK2 function can contribute to neurological, sensory, and vascular pathologies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Duane Allen, Chris T Bond, Rafael Luján, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SK2-long isoform directs synaptic localization and function of SK2-containing channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.2832"}], "href": "https://doi.org/10.1038/nn.2832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21602822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21602822"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmen Ballesteros-Merino, Mike Lin, Wendy W Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental profile of SK2 channel expression and function in CA1 neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hippocampus (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hipo.20986"}], "href": "https://doi.org/10.1002/hipo.20986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22072564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22072564"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Adrian M Fischl, Paula M Heron, Arnold J Stromberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activity-dependent genes in mouse olfactory sensory neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chem Senses (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/chemse/bju015"}], "href": "https://doi.org/10.1093/chemse/bju015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24692514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24692514"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Vidya Murthy, Stéphane F Maison, Julián Taranda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcn.2008.08.011"}], "href": "https://doi.org/10.1016/j.mcn.2008.08.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18848895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18848895"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "H K Fan, T X Luo, W D Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional interaction of Junctophilin 2 with small- conductance Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " -activated potassium channel subtype 2(SK2) in mouse cardiac myocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Physiol (Oxf) (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/apha.12986"}], "href": "https://doi.org/10.1111/apha.12986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29055091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29055091"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fanny Mochel, Agnès Rastetter, Berten Ceulemans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awaa346"}], "href": "https://doi.org/10.1093/brain/awaa346"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33242881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33242881"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jae-Jung Kim, Young-Mi Park, Dankyu Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2013.43"}], "href": "https://doi.org/10.1038/jhg.2013.43"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23677057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23677057"}]}]}]}
Synonyms	KCA2.2, SKCA 2, SKCA2, SK2, HSK2
Proteins	KCNN2_HUMAN
NCBI Gene ID	3781
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNN2 has 5,923 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 119 datasets.

Click the + buttons to view associations for KCNN2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNN2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by KCNN2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KCNN2 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KCNN2 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 KCNN2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNN2 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 KCNN2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNN2 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 KCNN2 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 KCNN2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNN2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNN2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNN2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNN2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving KCNN2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KCNN2 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 KCNN2 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 KCNN2 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 KCNN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNN2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNN2 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 KCNN2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNN2 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 KCNN2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KCNN2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of KCNN2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.