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

Summary

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: mouse all
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Genomic context

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_000019.10 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 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?

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.
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.
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.
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.
KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation.
Title: KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation.
Pancreatic KCa3.1 channels in health and disease.
Title: Pancreatic K(Ca)3.1 channels in health and disease.
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.
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.
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.
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	Compare labs

EBI GWAS Catalog

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

RH47242 (e-PCR)
- UniSTS:15114

SHGC-33130 (e-PCR)
- UniSTS:76577

D19S217 (e-PCR), detects polymorphism
- UniSTS:23953

D19S217 (e-PCR), detects polymorphism
- UniSTS:5269

D19S217 (e-PCR), detects polymorphism
- UniSTS:54513

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

NG_052672.1 RefSeqGene

Range

6167..20607

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1305

mRNA and Protein(s)

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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

43766533..43780973 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Related

ENST00000648053.1
XM_047438793.1 → XP_047294749.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X3

RNA

XR_935823.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

46589266..46619926 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

O15554, Q53XR4
XM_054320944.1 → XP_054176919.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X5

UniProtKB/Swiss-Prot

O15554, Q53XR4
XM_054320943.1 → XP_054176918.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X5

UniProtKB/Swiss-Prot

O15554, Q53XR4
XM_054320946.1 → XP_054176921.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X1
XM_054320947.1 → XP_054176922.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X2
XM_054320949.1 → XP_054176924.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X4
XM_054320948.1 → XP_054176923.1 intermediate conductance calcium-activated potassium channel protein 4 isoform X3