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

    Gene ID: 3749, updated on 28-Oct-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)

    Genotypes

    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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