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

Gene ID: 3783, updated on 14-Nov-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; hIK1; 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
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (43766533..43780973, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (46589266..46619926, complement)
RS_2024_09 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 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. KCa3.1-Dependent Hyperpolarization Enhances Intracellular Ca2+ Signaling Induced by fMLF in Differentiated U937 Cells. Penna A, et al. PLoS One, 2015. PMID 26418693, Free PMC Article
  2. Role of the potassium channel KCa3.1 in diabetic nephropathy. Huang C, et al. Clin Sci (Lond), 2014 Oct. PMID 24963668
  3. KCNN4 gene variant is associated with ileal Crohn's Disease in the Australian and New Zealand population. Simms LA, et al. Am J Gastroenterol, 2010 Oct. PMID 20407432
  4. An investigation of the occurrence and properties of the mitochondrial intermediate-conductance Ca2+-activated K+ channel mtKCa3.1. Sassi N, et al. Biochim Biophys Acta, 2010 Jun-Jul. PMID 20036632
  5. KCa3.1: a new player in progressive kidney disease. Huang C, et al. Curr Opin Nephrol Hypertens, 2015 Jan. PMID 25415613

See all (172) 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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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
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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)

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 calmodulin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables intermediate conductance calcium-activated potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables intermediate conductance calcium-activated potassium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables potassium channel activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
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 macropinocytosis IDA
Inferred from Direct Assay
more info
 PubMed 
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 transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in potassium ion transport TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein homotetramerization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of calcium ion import across plasma membrane IDA
Inferred from Direct Assay
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 ruffle membrane IDA
Inferred from Direct Assay
more info
 PubMed 
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
gardos channel
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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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_2024_08

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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