KCNC4 Gene

HGNC Family	Ion channels
Name	potassium channel, voltage gated Shaw related subfamily C, member 4
Description	The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. It generates atypical voltage-dependent transient current that may be important for neuronal excitability. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The KCNC4 gene encodes the Kv3.4 subunit of fast voltage‐gated potassium channels that play a critical role in regulating membrane excitability in both neurons and muscle. Kv3.4 channels activate rapidly and inactivate in a voltage‐dependent manner to shape action potential repolarization and control firing frequency. In the central nervous system, Kv3.4 channels are involved in defining the duration and repetitive firing properties of neurons, processes that underlie effective synaptic signaling. Dysregulation of Kv3.4 activity has been linked to neurodegenerative conditions; for example, increased Kv3.4 expression in Alzheimer’s disease may alter spike repolarization and contribute to aberrant synaptic transmission, while β‐amyloid peptides can up‐regulate Kv3.4 transcript and current levels via NF‐κB‐dependent pathways leading to enhanced neuronal vulnerability, effects that can be mitigated by specific channel inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, in peripheral sensory neurons, altered Kv3.4 channel expression and impaired inactivation dynamics have been implicated in the development of chronic pain following spinal cord injury, as reduced plasma membrane levels of Kv3.4 compromise proper action potential repolarization and promote repetitive firing in nociceptors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In skeletal muscle, Kv3.4 forms heteromeric complexes with accessory subunits such as MiRP2, which modulate channel kinetics and confer sensitivity to intracellular signals including pH changes and phosphorylation events; these interactions are linked to the pathogenesis of periodic paralysis by altering the muscle cell’s excitability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies demonstrate that KCNC4/Kv3.4 serves as a key regulator of electrical signaling in excitable tissues, with its tight control of activation/inactivation kinetics being essential for normal neuronal function and muscle excitability. Disruptions in Kv3.4 expression or modulation can contribute to neurodegeneration, aberrant pain signaling, and muscle pathologies, highlighting its therapeutic potential in several disease contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ester Angulo, Véronique Noé, Vicent Casadó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of the Kv3.4 potassium channel subunit in early stages of Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2004.02771.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2004.02771.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15485486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15485486"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A Pannaccione, F Boscia, A Scorziello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.107.034868"}], "href": "https://doi.org/10.1124/mol.107.034868"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17495071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17495071"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David M Ritter, Benjamin M Zemel, Tamara J Hala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1594-14.2015"}], "href": "https://doi.org/10.1523/JNEUROSCI.1594-14.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25609640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25609640"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Geoffrey W Abbott, Margaret H Butler, Steve A N Goldstein "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.05-5070com"}], "href": "https://doi.org/10.1096/fj.05-5070com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449802"}]}]}]}
Synonyms	C1ORF30, HKSHIIIC, KSHIIIC, KV3.4
Proteins	KCNC4_HUMAN
NCBI Gene ID	3749
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KCNC4 has 5,444 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for KCNC4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 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 KCNC4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KCNC4 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 KCNC4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KCNC4 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 KCNC4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KCNC4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KCNC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KCNC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing KCNC4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing KCNC4 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KCNC4 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 KCNC4 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 KCNC4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KCNC4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KCNC4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KCNC4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KCNC4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with KCNC4 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 KCNC4 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 KCNC4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KCNC4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KCNC4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KCNC4 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 KCNC4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of KCNC4 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 KCNC4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with KCNC4 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 KCNC4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with KCNC4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing KCNC4 from the GeneSigDB Published Gene Signatures dataset.