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

Summary

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

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_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Loss-of-function KCa2.2 mutations abolish channel activity.
Title: Loss-of-function K(Ca)2.2 mutations abolish channel activity.
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.
KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia.
Title: KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

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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

RH118957 (e-PCR)
- UniSTS:138242

NoName (e-PCR)
- UniSTS:486159

D5S2065 (e-PCR), detects polymorphism
- UniSTS:26179

NoName (e-PCR)
- UniSTS:492633

SHGC-142407 (e-PCR)
- UniSTS:171442

KCNN2_3214 (e-PCR)
- UniSTS:462292

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)

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
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
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

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
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

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

114055978..114496496

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060929.1 Alternate T2T-CHM13v2.0

Range

114568913..115009369

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054352563.1 → XP_054208538.1 small conductance calcium-activated potassium channel protein 2 isoform X2
XM_054352562.1 → XP_054208537.1 small conductance calcium-activated potassium channel protein 2 isoform X1
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

NM_001278204.2: Suppressed sequence

Description

NM_001278204.2: This RefSeq was removed because it is a nonsense-mediated mRNA decay (NMD) candidate.