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KCNC4 potassium voltage-gated channel subfamily C member 4 [ Homo sapiens (human) ]

Gene ID: 3749, updated on 2-Nov-2024

Summary

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Official Symbol
KCNC4provided by HGNC
Official Full Name
potassium voltage-gated channel subfamily C member 4provided by HGNC
Primary source
HGNC:HGNC:6236
See related
Ensembl:ENSG00000116396 MIM:176265; AllianceGenome:HGNC:6236
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KV3.4; C1orf30; KSHIIIC; HKSHIIIC
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 4.0), kidney (RPKM 3.0) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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See KCNC4 in Genome Data Viewer
Location:
1p13.3
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (110210314..110284080)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (110225284..110300705)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (110752936..110776666)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene solute carrier family 6 member 17 Neighboring gene SLC6A17 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110740169-110740669 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1462 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1169 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1170 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1171 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110754533-110755421 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1463 Neighboring gene KCNC4 divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110777544-110778044 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:110778045-110778545 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1172 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1465 Neighboring gene uncharacterized LOC124900436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1466 Neighboring gene RBM15 antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:110837163-110837321 Neighboring gene uncharacterized LOC124904276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1467 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1173 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1468 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:110882428-110883166 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:110883828-110884393 Neighboring gene RNA binding motif protein 15

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Expression of the voltage-gated potassium channel Kv3.4 in oral leucoplakias and oral squamous cell carcinomas. Fernández-Valle Á, et al. Histopathology, 2016 Jul. PMID 26648458
  2. Expression and clinical significance of the Kv3.4 potassium channel subunit in the development and progression of head and neck squamous cell carcinomas. Menéndez ST, et al. J Pathol, 2010 Aug. PMID 20593490
  3. Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons. Alexander TD, et al. J Neurosci, 2022 Nov 16. PMID 36198500, Free PMC Article
  4. Kv3.4, a key signalling molecule controlling the cell cycle and proliferation of human arterial smooth muscle cells. Leblanc N. Cardiovasc Res, 2010 Jun 1. PMID 20378681
  5. Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells. Miguel-Velado E, et al. Cardiovasc Res, 2010 Jun 1. PMID 20093253

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons.
    Title: Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons.
  2. PKCepsilon associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
    Title: PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
  3. HIF-1alpha regulates the invasion, migration and proliferation of oral cancer cells by regulating Kv3.4 expression.
    Title: HIF-1α Regulates Proliferation and Invasion of Oral Cancer Cells through Kv3.4 Channel.
  4. This study provides original evidence to demonstrate the early occurrence and high prevalence of abnormal Kv3.4 expression in oral leucoplakias. Our results support a role for Kv3.4 potassium channel in OSCC tumorigenesis rather than tumour progression and disease outcome.
    Title: Expression of the voltage-gated potassium channel Kv3.4 in oral leucoplakias and oral squamous cell carcinomas.
  5. These results suggest a novel peripheral mechanism of post-spinal cord injury pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions.
    Title: Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury.
  6. Ionizing radiation-induced G2/M arrest was preceded by activation of Kv3.4-like voltage-gated potassium channels.
    Title: Kv3.4 potassium channel-mediated electrosignaling controls cell cycle and survival of irradiated leukemia cells.
  7. these data suggest that Kv3.4 and Cav1.2 may act together to control Ca(2) -dependent electrical activity of pioneer axons and play important roles during axon pathfinding.
    Title: Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.
  8. Although all KV3 subunit transcripts are significantly expressed at embryonic age in whole mouse brain extracts, only KV3.1, KV3.2 and KV3.4 subunit transgenic proteins are present.
    Title: Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
  9. Kv3.4 channels exert a permissive role in the cell cycle progression of proliferating uterine vascular smooth cells.
    Title: Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells.
  10. Kv3.4 was overexpressed in early stages of Alzheimer disease and in advanced stages was present at high levels in neurodegenerative structures. This subunit regulates delayed-rectifier currents, primary determinants of spike repolarization in neurones
    Title: Up-regulation of the Kv3.4 potassium channel subunit in early stages of Alzheimer's disease.
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study of self-rated health.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126818

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables delayed rectifier potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables potassium channel activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables voltage-gated potassium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in action potential IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in chemical synaptic transmission TAS
Traceable Author Statement
more info
  
involved_in potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in potassium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein homooligomerization IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in axon terminus IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in dendrite membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in neuronal cell body membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
is_active_in postsynaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in presynaptic membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of voltage-gated potassium channel complex IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
voltage-gated potassium channel KCNC4
Names
K+ channel subunit
potassium channel, voltage gated Shaw related subfamily C, member 4
potassium voltage-gated channel, Shaw-related subfamily, member 4
voltage-gated potassium channel subunit KV3.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001039574.3 → NP_001034663.1  voltage-gated potassium channel KCNC4 isoform c

    See identical proteins and their annotated locations for NP_001034663.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site that results in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (c) has a shorter and distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AK310193, AL137790, BC025377, BX098184, CK823243, DA111555, DA404087
    Consensus CDS
    CCDS44193.1
    UniProtKB/Swiss-Prot
    Q03721
    Related
    ENSP00000393655.2, ENST00000438661.3
    Conserved Domains (5) summary
    smart00225
    Location:38 → 151
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:276 → 483
    Ion_trans; Ion transport protein
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam07885
    Location:426 → 480
    Ion_trans_2; Ion channel
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  2. NM_001377330.1 → NP_001364259.1  voltage-gated potassium channel KCNC4 isoform d

    Status: REVIEWED

    Source sequence(s)
    AL137790
    Consensus CDS
    CCDS91021.1
    UniProtKB/TrEMBL
    H7BZ66
    Related
    ENSP00000388029.3, ENST00000413138.7
    Conserved Domains (3) summary
    cd18415
    Location:35 → 158
    BTB_KCNC2_4; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC2 and KCNC4
    pfam00520
    Location:225 → 483
    Ion_trans; Ion transport protein
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  3. NM_001377331.1 → NP_001364260.1  voltage-gated potassium channel KCNC4 isoform e

    Status: REVIEWED

    Source sequence(s)
    AL137790
    Conserved Domains (2) summary
    cd18415
    Location:35 → 158
    BTB_KCNC2_4; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium voltage-gated channel subfamily C members KCNC2 and KCNC4
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  4. NM_004978.6 → NP_004969.2  voltage-gated potassium channel KCNC4 isoform a

    See identical proteins and their annotated locations for NP_004969.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).
    Source sequence(s)
    AK125567, AK310193, AL137790, BC025377, DA111555, DA404087, DA936036
    Consensus CDS
    CCDS821.1
    UniProtKB/Swiss-Prot
    Q03721, Q3MIM4, Q5TBI6
    Related
    ENSP00000358802.3, ENST00000369787.7
    Conserved Domains (5) summary
    smart00225
    Location:38 → 151
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:276 → 483
    Ion_trans; Ion transport protein
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam07885
    Location:426 → 480
    Ion_trans_2; Ion channel
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

RNA

  1. NR_036437.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate segment in the 3' region, compared to variant 1. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK310193, AL137790, BC025377, BM765446, DA111555, DA404087, DA902474, DA936036

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    110210314..110284080
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419679.1 → XP_047275635.1  voltage-gated potassium channel KCNC4 isoform X3

  2. XM_006710625.5 → XP_006710688.1  voltage-gated potassium channel KCNC4 isoform X1

    Conserved Domains (5) summary
    smart00225
    Location:38 → 151
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:276 → 483
    Ion_trans; Ion transport protein
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam07885
    Location:426 → 480
    Ion_trans_2; Ion channel
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  3. XM_011541401.4 → XP_011539703.1  voltage-gated potassium channel KCNC4 isoform X2

    Conserved Domains (5) summary
    smart00225
    Location:38 → 151
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam00520
    Location:276 → 483
    Ion_trans; Ion transport protein
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam07885
    Location:426 → 473
    Ion_trans_2; Ion channel
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  4. XM_047419680.1 → XP_047275636.1  voltage-gated potassium channel KCNC4 isoform X5

  5. XM_011541404.3 → XP_011539706.1  voltage-gated potassium channel KCNC4 isoform X4

    Conserved Domains (3) summary
    smart00225
    Location:38 → 151
    BTB; Broad-Complex, Tramtrack and Bric a brac
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

  6. XM_024446790.2 → XP_024302558.1  voltage-gated potassium channel KCNC4 isoform X6

    Conserved Domains (3) summary
    pfam00520
    Location:225 → 483
    Ion_trans; Ion transport protein
    pfam02214
    Location:38 → 143
    BTB_2; BTB/POZ domain
    pfam11404
    Location:1 → 29
    Potassium_chann; Potassium voltage-gated channel

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    110225284..110300705
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336437.1 → XP_054192412.1  voltage-gated potassium channel KCNC4 isoform X3

  2. XM_054336435.1 → XP_054192410.1  voltage-gated potassium channel KCNC4 isoform X1

  3. XM_054336436.1 → XP_054192411.1  voltage-gated potassium channel KCNC4 isoform X2

  4. XM_054336439.1 → XP_054192414.1  voltage-gated potassium channel KCNC4 isoform X5

  5. XM_054336438.1 → XP_054192413.1  voltage-gated potassium channel KCNC4 isoform X4

  6. XM_054336440.1 → XP_054192415.1  voltage-gated potassium channel KCNC4 isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_153763.2: Suppressed sequence

    Description
    NM_153763.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein, and the transcript appears to retain intronic sequence.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q03721.2 GenPept UniProtKB/Swiss-Prot:Q03721

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