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    KCNN2 potassium calcium-activated channel subfamily N member 2 [ Homo sapiens (human) ]

    Gene ID: 3781, updated on 28-Oct-2024

    Summary

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    Official Symbol
    KCNN2provided by HGNC
    Official Full Name
    potassium calcium-activated channel subfamily N member 2provided by HGNC
    Primary source
    HGNC:HGNC:6291
    See related
    Ensembl:ENSG00000080709 MIM:605879; AllianceGenome:HGNC:6291
    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
    SK2; hSK2; DYT34; SKCA2; KCa2.2; NEDMAB; SKCa 2
    Summary
    Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The protein encoded by this gene is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene is a member of the KCNN family of potassium channel genes. The encoded protein is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
    Expression
    Biased expression in adrenal (RPKM 4.9), liver (RPKM 3.5) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNN2 in Genome Data Viewer
    Location:
    5q22.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (114055978..114496496)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (114568913..115009369)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (113391675..113832193)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105379127 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:113111806-113112399 Neighboring gene uncharacterized LOC124901047 Neighboring gene NANOG hESC enhancer GRCh37_chr5:113182507-113183008 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:113270609-113270841 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:113374279-113374780 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr5:113374781-113375280 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:113459198-113459408 Neighboring gene NANOG hESC enhancer GRCh37_chr5:113590875-113591386 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:113613789-113614290 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:113614291-113614790 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:113643487-113644315 Neighboring gene RN7SK pseudogene 89 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:113695880-113696796 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16244 Neighboring gene NANOG hESC enhancer GRCh37_chr5:113724412-113724913 Neighboring gene uncharacterized LOC101927078 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22922 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:113880373-113880872 Neighboring gene long intergenic non-protein coding RNA 1957 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:114117551-114118374 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:114118375-114119196 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:114364005-114364746 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:114364747-114365486 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:114368052-114369251 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22923 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:114404076-114405275 Neighboring gene Sharpr-MPRA regulatory region 9285 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:114426221-114426720 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:114426721-114427222 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16245 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16246 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22925 Neighboring gene tripartite motif containing 36

    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. Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles. Chang PC, et al. J Am Heart Assoc, 2013 Jan 3. PMID 23525437, Free PMC Article
    2. SK2 encodes the apamin-sensitive Ca(2+)-activated K(+) channels in the human leukemic T cell line, Jurkat. Jäger H, et al. FEBS Lett, 2000 Mar 10. PMID 10713270
    3. Ca2+-activated K+ channels in human leukemic Jurkat T cells. Molecular cloning, biochemical and functional characterization. Desai R, et al. J Biol Chem, 2000 Dec 22. PMID 10991935
    4. A Novel KCNN2 Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis. d'Apolito M, et al. Genes (Basel), 2023 Jun 29. PMID 37510285, Free PMC Article
    5. Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders. Mochel F, et al. Brain, 2020 Dec 1. PMID 33242881

    See all (47) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A Novel KCNN2 Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis.
      Title: A Novel KCNN2 Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis.
    2. Loss-of-function KCa2.2 mutations abolish channel activity.
      Title: Loss-of-function K(Ca)2.2 mutations abolish channel activity.
    3. Preferential formation of human heteromeric SK2:SK3 channels limits homomeric SK channel assembly and function.
      Title: Preferential formation of human heteromeric SK2:SK3 channels limits homomeric SK channel assembly and function.
    4. KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia.
      Title: KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia.
    5. Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders.
      Title: Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders.
    6. HDAC2-dependent remodeling of KCa2.2 (KCNN2) and KCa2.3 (KCNN3) K(+) channels in atrial fibrillation with concomitant heart failure.
      Title: HDAC2-dependent remodeling of K(Ca)2.2 (KCNN2) and K(Ca)2.3 (KCNN3) K(+) channels in atrial fibrillation with concomitant heart failure.
    7. SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.
      Title: SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.
    8. Immuno-visualization of the subcellular localization of SK2 and SK3 subunits showed a high degree of colocalization, consistent with the formation of heteromeric SK2/SK3 channels.
      Title: Role of SK channel activation in determining the action potential configuration in freshly isolated human atrial myocytes from the SKArF study.
    9. Junctophilin 2, as junctional membrane complex (JMC) protein, is an important regulator of the cardiac SK channels
      Title: Functional interaction of Junctophilin 2 with small- conductance Ca(2+) -activated potassium channel subtype 2(SK2) in mouse cardiac myocytes.
    10. SK current is increased via the enhanced activation of CaMKII in patients with atrial fibrillation.
      Title: Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) Increases Small-Conductance Ca2+-Activated K+ Current in Patients with Chronic Atrial Fibrillation.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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
    Dystonia 34, myoclonic
    MedGen: C5676907 OMIM: 619724 GeneReviews: Not available
    		not available
    Neurodevelopmental disorder with or without variable movement or behavioral abnormalities
    MedGen: C5676908 OMIM: 619725 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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 alpha-actinin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 inward rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein domain specific binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables small conductance calcium-activated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables small conductance calcium-activated potassium channel activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in membrane repolarization during atrial cardiac muscle cell action potential ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    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 transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in potassium ion transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in potassium ion transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Z disc ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in dendritic spine IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    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
    		  

    General protein information

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    Preferred Names
    small conductance calcium-activated potassium channel protein 2
    Names
    apamin-sensitive small-conductance Ca2+-activated potassium channel
    potassium channel, calcium activated intermediate/small conductance subfamily N alpha, member 2
    potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2
    small conductance calcium-activated potassium channel 2

    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_001372233.1 → NP_001359162.1  small conductance calcium-activated potassium channel protein 2 isoform c

      Status: REVIEWED

      Source sequence(s)
      AC025761, AC094088, AC106789, AC109482, AC113364, KF459898
      Consensus CDS
      CCDS93760.1
      UniProtKB/TrEMBL
      A0A3F2YNY5
      Related
      ENSP00000427120.4, ENST00000512097.10
      Conserved Domains (3) summary
      pfam02888
      Location:690 → 762
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:402 → 509
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:597 → 676
      Ion_trans_2; Ion channel

    2. NM_021614.4 → NP_067627.3  small conductance calcium-activated potassium channel protein 2 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).
      Source sequence(s)
      AK289948, BC015371, BC117454, DC374170
      Consensus CDS
      CCDS4114.2
      UniProtKB/TrEMBL
      A0A669KBH3
      Related
      ENSP00000501239.1, ENST00000673685.1
      Conserved Domains (3) summary
      pfam02888
      Location:624 → 696
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:336 → 443
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:531 → 610
      Ion_trans_2; Ion channel

    3. NM_170775.3 → NP_740721.1  small conductance calcium-activated potassium channel protein 2 isoform b

      See identical proteins and their annotated locations for NP_740721.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region and initiates translation at a downstream start codon, compared to variant 1. Variants 2 and 3 encode the same isoform (b), which is shorter at the N-terminus compared to isoform a.
      Source sequence(s)
      AC109482, BC015371, BG477734
      Consensus CDS
      CCDS43352.1
      UniProtKB/Swiss-Prot
      Q9H2S1
      Related
      ENSP00000421439.1, ENST00000503706.5
      Conserved Domains (2) summary
      smart01053
      Location:64 → 139
      CaMBD; Calmodulin binding domain
      pfam07885
      Location:1 → 50
      Ion_trans_2; Ion channel

    RNA

    1. NR_103458.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate 5' exon structure and contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC109482, BC015371, BC040722, BG477734

    2. NR_174097.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC025761, AC109482, KF459898

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      114055978..114496496
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047417166.1 → XP_047273122.1  small conductance calcium-activated potassium channel protein 2 isoform X2

    2. XM_011543389.2 → XP_011541691.1  small conductance calcium-activated potassium channel protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011541691.1

      UniProtKB/TrEMBL
      A0A3F2YNY5
      Conserved Domains (3) summary
      pfam02888
      Location:690 → 762
      CaMBD; Calmodulin binding domain
      pfam03530
      Location:402 → 509
      SK_channel; Calcium-activated SK potassium channel
      pfam07885
      Location:597 → 676
      Ion_trans_2; Ion channel

    3. XM_017009457.2 → XP_016864946.1  small conductance calcium-activated potassium channel protein 2 isoform X3

      Conserved Domains (2) summary
      pfam02888
      Location:108 → 180
      CaMBD; Calmodulin binding domain
      pfam07885
      Location:40 → 94
      Ion_trans_2; Ion channel

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      114568913..115009369
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054352563.1 → XP_054208538.1  small conductance calcium-activated potassium channel protein 2 isoform X2

    2. XM_054352562.1 → XP_054208537.1  small conductance calcium-activated potassium channel protein 2 isoform X1

    3. XM_054352564.1 → XP_054208539.1  small conductance calcium-activated potassium channel protein 2 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001278204.2: Suppressed sequence

      Description
      NM_001278204.2: This RefSeq was removed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H2S1.2 GenPept UniProtKB/Swiss-Prot:Q9H2S1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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