KCNK4 potassium two pore domain channel subfamily K member 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNK4provided by HGNC
Official Full Name: potassium two pore domain channel subfamily K member 4provided by HGNC
Primary source: HGNC:HGNC:6279
See related: Ensembl:ENSG00000182450 MIM:605720; AllianceGenome:HGNC:6279
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: FHEIG; TRAAK; K2p4.1; TRAAK1
Summary: This gene encodes a member of the TWIK-related arachidonic acid-stimulated two pore potassium channel subfamily. The encoded protein homodimerizes and functions as an outwardly rectifying channel. This channel is regulated by polyunsaturated fatty acids, temperature and mechanical deformation of the lipid membrane. This protein is expressed primarily in neural tissues and may be involved in regulating the noxious input threshold in dorsal root ganglia neurons. Alternate splicing results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream testis expressed 40 (TEX40) gene, as represented in GeneID: 106780802. [provided by RefSeq, Nov 2015]
Expression: Biased expression in brain (RPKM 1.0), placenta (RPKM 0.2) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (64291302..64300031)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (64281266..64289999)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (64058774..64067503)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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 recurrent KCNK4 variant in a dominant pedigree with hypertrichosis and gingival fibromatosis syndrome: Variable phenotypic expressivity and insights on patients' dental management.
Title: A recurrent KCNK4 variant in a dominant pedigree with hypertrichosis and gingival fibromatosis syndrome: Variable phenotypic expressivity and insights on patients' dental management.
Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
Title: Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
Physical basis for distinct basal and mechanically gated activity of the human K(+) channel TRAAK.
Title: Physical basis for distinct basal and mechanically gated activity of the human K(+) channel TRAAK.
Selective regulation of human TRAAK channels by biologically active phospholipids.
Title: Selective regulation of human TRAAK channels by biologically active phospholipids.
TRAAK, TREK1 and TREK2 are robustly mechanosensitive K+-selective channels of the K2P family and are modulated by chemical and physical stimuli including lipids, lysolipids, arachidonic acid and other polyunsaturated fatty acids.
Title: Decreased expression of TRAAK channels in Hirschsprung's disease: a possible cause of postoperative dysmotility.
The pleiotropic effect of dysregulated KCNK4 function.
Title: Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome.
Functional alanine-mutagenesis screens of TASK-1 and TRAAK were used to build an in silico model of the TASK-1 cap.
Title: Functional mutagenesis screens reveal the 'cap structure' formation in disulfide-bridge free TASK channels.
KCNK4 promoter methylation is associated with Breast Cancer.
Title: Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study.
How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2.
Title: How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2.
findings uncover a unique aspect of potassium channel modulation, indicate a means for how the channel C-terminal cytoplasmic domain affects the C-type gate, and suggest how lipids and bilayer inner leaflet deformations gate the channel.
Title: Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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
Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome MedGen: C5193066 OMIM: 618381 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Readthrough KCNK4-CATSPERZ

Readthrough gene: KCNK4-CATSPERZ, Included gene: CATSPERZ

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables mechanosensitive potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables outward rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium ion leak channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables temperature-gated cation channel activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cellular response to alkaline pH	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to fatty acid	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to mechanical stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to temperature stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of mechanical stimulus involved in sensory perception of touch	ISS Inferred from Sequence or Structural Similarity more info
involved_in memory	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 sensory perception of pain	ISS Inferred from Sequence or Structural Similarity more info
involved_in sensory perception of temperature stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in stabilization of membrane potential	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: potassium channel subfamily K member 4

Names: K2P4.1 potassium channel; TWIK-related arachidonic acid-stimulated potassium channel protein; potassium channel, subfamily K, member 4; potassium channel, two pore domain subfamily K, member 4; two pore K(+) channel KT4.1; two pore K+ channel KT4.1; two pore potassium channel KT4.1

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_001317090.2 → NP_001304019.1 potassium channel subfamily K member 4

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 2. Both variants 2 and 4 encode the same protein.

Source sequence(s)

AP001453, BC110327

Consensus CDS

CCDS8067.1

UniProtKB/Swiss-Prot

B5TJL1, Q96T94, Q9NYG8

UniProtKB/TrEMBL

Q2YDA1

Related

ENSP00000378033.2, ENST00000394525.6

Conserved Domains (1) summary

pfam07885
Location:88 → 142

Ion_trans_2; Ion channel
NM_033310.3 → NP_201567.1 potassium channel subfamily K member 4

See identical proteins and their annotated locations for NP_201567.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the functional protein.

Source sequence(s)

AF259500, AP001453, BC067791, BC110327, DB273064

Consensus CDS

CCDS8067.1

UniProtKB/Swiss-Prot

B5TJL1, Q96T94, Q9NYG8

UniProtKB/TrEMBL

Q2YDA1

Related

ENSP00000402797.2, ENST00000422670.7

Conserved Domains (1) summary

pfam07885
Location:88 → 142

Ion_trans_2; Ion channel

RNA

NR_133660.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate 5' most exon, lacks an internal exon and uses an alternate splice site in an internal exon compared to variant 2. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AP001453, BC067791

Related

ENST00000538767.1
NR_133661.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate 5' most exon and uses an alternate splice site in an internal exon compared to variant 2. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AP001453, BC033577

Related

ENST00000541349.5