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

Gene ID: 3781, updated on 5-Mar-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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Location:
5q22.3
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (114055978..114496496)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (114568913..115009369)
105.20220307 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
  • 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. Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders. Mochel F, et al. Brain, 2020 Dec 1. PMID 33242881
  2. SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases. Sun J, et al. Biochim Biophys Acta Mol Cell Res, 2020 Dec. PMID 32860835, Free PMC Article
  3. KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia. Balint B, et al. Eur J Neurol, 2020 Aug. PMID 32212350
  4. KCNN2 polymorphisms and cardiac tachyarrhythmias. Yu CC, et al. Medicine (Baltimore), 2016 Jul. PMID 27442679, Free PMC Article
  5. Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain. Willis M, et al. Brain Struct Funct, 2017 Mar. PMID 27357310, Free PMC Article

See all (44) 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 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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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.

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_2023_10

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

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