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    KCNN4 potassium calcium-activated channel subfamily N member 4 [ Homo sapiens (human) ]

    Gene ID: 3783, updated on 20-May-2024

    Summary

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    Official Symbol
    KCNN4provided by HGNC
    Official Full Name
    potassium calcium-activated channel subfamily N member 4provided by HGNC
    Primary source
    HGNC:HGNC:6293
    See related
    Ensembl:ENSG00000104783 MIM:602754; AllianceGenome:HGNC:6293
    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
    IK; IK1; SK4; DHS2; KCA4; hSK4; IKCA1; hKCa4; KCa3.1; hIKCa1
    Summary
    The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization, which promotes calcium influx. The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in salivary gland (RPKM 25.8), stomach (RPKM 13.6) and 10 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNN4 in Genome Data Viewer
    Location:
    19q13.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (43766533..43780973, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (46589266..46619926, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (44270685..44285125, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44220201-44220701 Neighboring gene immunity related GTPase cinema Neighboring gene SMG9 nonsense mediated mRNA decay factor Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10728 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14736 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10729 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:44268619-44268844 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14737 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14738 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14739 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:44270408-44270571 Neighboring gene CRISPRi-validated cis-regulatory element KCNN4 K1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44281957-44282457 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10730 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44283513-44284012 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14740 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10731 Neighboring gene CRISPRi-validated cis-regulatory element chr19.4589 Neighboring gene Sharpr-MPRA regulatory region 14970 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44288851-44289352 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:44289353-44289852 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14743 Neighboring gene LY6/PLAUR domain containing 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14744 Neighboring gene zinc finger protein 283

    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
    • 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. Pancreatic K(Ca)3.1 channels in health and disease. Soret B, et al. Biol Chem, 2023 Mar 28. PMID 36571487
    2. Downregulation of IL-8 and IL-10 by the Activation of Ca(2+)-Activated K(+) Channel K(Ca)3.1 in THP-1-Derived M(2) Macrophages. Ohya S, et al. Int J Mol Sci, 2022 Aug 3. PMID 35955737, Free PMC Article
    3. KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism. Fan J, et al. Int J Mol Sci, 2022 Jun 23. PMID 35805963, Free PMC Article
    4. Altered K(Ca)3.1 expression following burn injury and the therapeutic potential of TRAM-34 in post-burn hypertrophic scar formation. Seo CH, et al. Transl Res, 2021 Oct. PMID 33905948
    5. KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways. Xu P, et al. Cancer Biomark, 2021. PMID 33896824

    See all (164) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca[2+]-Dependent Activation of the Calcium-Gated Potassium SK4 Channel.
      Title: Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca(2+)-Dependent Activation of the Calcium-Gated Potassium SK4 Channel.
    2. Overexpression of KCNN4 channels in principal neurons produces an anti-seizure effect without reducing their coding ability.
      Title: Overexpression of KCNN4 channels in principal neurons produces an anti-seizure effect without reducing their coding ability.
    3. The Gardos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.
      Title: The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.
    4. A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.
      Title: A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.
    5. KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation.
      Title: KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation.
    6. Pancreatic KCa3.1 channels in health and disease.
      Title: Pancreatic K(Ca)3.1 channels in health and disease.
    7. Downregulation of IL-8 and IL-10 by the Activation of Ca(2+)-Activated K(+) Channel KCa3.1 in THP-1-Derived M2 Macrophages.
      Title: Downregulation of IL-8 and IL-10 by the Activation of Ca(2+)-Activated K(+) Channel K(Ca)3.1 in THP-1-Derived M(2) Macrophages.
    8. KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism.
      Title: KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism.
    9. KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways.
      Title: KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways.
    10. SK4 oncochannels regulate calcium entry and promote cell migration in KRAS-mutated colorectal cancer.
      Title: SK4 oncochannels regulate calcium entry and promote cell migration in KRAS-mutated colorectal cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (146)

    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

    Associated conditions

    Description Tests
    Dehydrated hereditary stomatocytosis 2
    MedGen: C4225242 OMIM: 616689 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium-activated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calmodulin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables intermediate conductance calcium-activated potassium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables potassium channel activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in calcium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cell volume homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in defense response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in establishment of localization in cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in immune system process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phospholipid translocation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of potassium ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in positive regulation of protein secretion IEA
    Inferred from Electronic Annotation
    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 saliva secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in stabilization of membrane potential IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in neuron projection IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in neuronal cell body IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of voltage-gated potassium channel complex IC
    Inferred by Curator
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    intermediate conductance calcium-activated potassium channel protein 4
    Names
    SKCa 4
    SKCa4
    intermediate-conductance Ca2+-activated K+ channel, KCa3.1
    potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 4
    potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4
    putative Gardos channel
    putative erythrocyte intermediate conductance calcium-activated potassium Gardos channel
    small conductance calcium-activated potassium channel 4

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_052672.1 RefSeqGene

      Range
      6167..20607
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1305

    mRNA and Protein(s)

    1. NM_002250.3 → NP_002241.1  intermediate conductance calcium-activated potassium channel protein 4

      See identical proteins and their annotated locations for NP_002241.1

      Status: REVIEWED

      Source sequence(s)
      AF022797, AF033021
      Consensus CDS
      CCDS12630.1
      UniProtKB/Swiss-Prot
      O15554, Q53XR4
      Related
      ENSP00000496939.1, ENST00000648319.1
      Conserved Domains (3) summary
      smart01053
      Location:304 → 376
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:15 → 122
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:237 → 290
      Ion_trans_2; Ion channel

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      43766533..43780973 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005258882.3 → XP_005258939.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X1

      Conserved Domains (3) summary
      smart01053
      Location:272 → 344
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:15 → 90
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:205 → 258
      Ion_trans_2; Ion channel

    2. XM_005258883.3 → XP_005258940.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X2

      Conserved Domains (2) summary
      smart01053
      Location:241 → 313
      CaMBD; Calmodulin binding domain
      pfam07885
      Location:174 → 227
      Ion_trans_2; Ion channel

    3. XM_047438794.1 → XP_047294750.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X4

      Related
      ENST00000648053.1

    4. XM_047438793.1 → XP_047294749.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X3

    RNA

    1. XR_935823.2 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      46589266..46619926 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320945.1 → XP_054176920.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X5

      UniProtKB/Swiss-Prot
      O15554, Q53XR4

    2. XM_054320944.1 → XP_054176919.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X5

      UniProtKB/Swiss-Prot
      O15554, Q53XR4

    3. XM_054320943.1 → XP_054176918.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X5

      UniProtKB/Swiss-Prot
      O15554, Q53XR4

    4. XM_054320946.1 → XP_054176921.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X1

    5. XM_054320947.1 → XP_054176922.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X2

    6. XM_054320949.1 → XP_054176924.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X4

    7. XM_054320948.1 → XP_054176923.1  intermediate conductance calcium-activated potassium channel protein 4 isoform X3

    RNA

    1. XR_008485146.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15554.1 GenPept UniProtKB/Swiss-Prot:O15554

    Gene LinkOut

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