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Aliases for KCNK4 Gene

Aliases for KCNK4 Gene

  • Potassium Two Pore Domain Channel Subfamily K Member 4 2 3 5
  • TWIK-Related Arachidonic Acid-Stimulated Potassium Channel Protein 3 4
  • Potassium Channel, Two Pore Domain Subfamily K, Member 4 2 3
  • Potassium Channel, Subfamily K, Member 4 2 3
  • Two Pore Potassium Channel KT4.1 3 4
  • Two Pore K(+) Channel KT4.1 3 4
  • TRAAK 3 4
  • Potassium Channel Subfamily K Member 4 3
  • Two Pore K+ Channel KT4.1 3
  • K2P4.1 Potassium Channel 3
  • K2p4.1 3
  • TRAAK1 3

External Ids for KCNK4 Gene

Previous GeneCards Identifiers for KCNK4 Gene

  • GC11P066574
  • GC11P065740
  • GC11P064309
  • GC11P063834
  • GC11P063815
  • GC11P064058
  • GC11P060386

Summaries for KCNK4 Gene

Entrez Gene Summary for KCNK4 Gene

  • 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]

GeneCards Summary for KCNK4 Gene

KCNK4 (Potassium Two Pore Domain Channel Subfamily K Member 4) is a Protein Coding gene. Diseases associated with KCNK4 include Dentin Sensitivity. Among its related pathways are Cardiac conduction and Neuropathic Pain-Signaling in Dorsal Horn Neurons. GO annotations related to this gene include ion channel activity and voltage-gated ion channel activity. An important paralog of this gene is KCNK10.

UniProtKB/Swiss-Prot for KCNK4 Gene

  • Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity).

Tocris Summary for KCNK4 Gene

Gene Wiki entry for KCNK4 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KCNK4 Gene

Genomics for KCNK4 Gene

Regulatory Elements for KCNK4 Gene

Enhancers for KCNK4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11G064237 1.4 ENCODE dbSUPER 14.6 -46.0 -45984 16.6 CREB3L1 MLX AGO1 DMAP1 FEZF1 YY1 ZNF143 ZNF263 SP3 NFYC ENSG00000257086 TRMT112 TRPT1 ZFPL1 PPP1R14B LOC102723878 VEGFB KCNK4 PLCB3 FERMT3
GH11G064267 1.4 ENCODE dbSUPER 12.8 -20.6 -20603 7.2 CREB3L1 AGO1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 MCM3 NFYC ZFPL1 TRMT112 PLCB3 POLA2 LOC102723878 TRPT1 ENSG00000257086 KCNK4 DNAJC4 ESRRA
GH11G064320 1.4 Ensembl ENCODE dbSUPER 12.2 +31.8 31818 5.3 HDAC1 KLF17 NFXL1 RAD21 ZNF366 EGR1 SCRT2 EGR2 ZNF263 ZBTB2 PLCB3 LOC102723878 ENSG00000257086 CATSPERZ ENSG00000207024 KCNK4-TEX40 KCNK4 BAD GPR137 TRMT112
GH11G064205 1.4 ENCODE dbSUPER 11.5 -83.7 -83707 4.4 HDGF PKNOX1 CREB3L1 ARNT AGO1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZFPL1 TRPT1 ENSG00000257086 PLCB3 TRMT112 GPR137 BAD KCNK4-TEX40 KCNK4 ENSG00000207024
GH11G064977 0.9 ENCODE 14.4 +686.5 686522 0.2 NFRKB ZSCAN9 ZNF335 TCF12 ZNF766 IKZF2 MIER1 GATAD2B MIER2 ELF1 KCNK4 OTUB1 CTSW MAJIN PIR50372
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around KCNK4 on UCSC Golden Path with GeneCards custom track

Genomic Location for KCNK4 Gene

Chromosome:
11
Start:
64,291,302 bp from pter
End:
64,300,031 bp from pter
Size:
8,730 bases
Orientation:
Plus strand

Genomic View for KCNK4 Gene

Genes around KCNK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KCNK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KCNK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KCNK4 Gene

Proteins for KCNK4 Gene

  • Protein details for KCNK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NYG8-KCNK4_HUMAN
    Recommended name:
    Potassium channel subfamily K member 4
    Protein Accession:
    Q9NYG8
    Secondary Accessions:
    • B5TJL1
    • Q96T94

    Protein attributes for KCNK4 Gene

    Size:
    393 amino acids
    Molecular mass:
    42704 Da
    Quaternary structure:
    • Homodimer; disulfide-linked.

    Three dimensional structures from OCA and Proteopedia for KCNK4 Gene

    Alternative splice isoforms for KCNK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KCNK4 Gene

Post-translational modifications for KCNK4 Gene

Other Protein References for KCNK4 Gene

No data available for DME Specific Peptides for KCNK4 Gene

Domains & Families for KCNK4 Gene

Gene Families for KCNK4 Gene

Suggested Antigen Peptide Sequences for KCNK4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9NYG8

UniProtKB/Swiss-Prot:

KCNK4_HUMAN :
  • Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix.
Domain:
  • Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix.
  • Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
genes like me logo Genes that share domains with KCNK4: view

Function for KCNK4 Gene

Molecular function for KCNK4 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by arachidonic acid.
UniProtKB/Swiss-Prot Function:
Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity).

Gene Ontology (GO) - Molecular Function for KCNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005267 potassium channel activity TAS,IDA 22282805
GO:0097604 temperature-gated cation channel activity ISS --
GO:0098782 mechanically-gated potassium channel activity IDA 22282805
genes like me logo Genes that share ontologies with KCNK4: view
genes like me logo Genes that share phenotypes with KCNK4: view

Animal Models for KCNK4 Gene

MGI Knock Outs for KCNK4:

Animal Model Products

  • Taconic Biosciences Mouse Models for KCNK4

CRISPR Products

miRNA for KCNK4 Gene

miRTarBase miRNAs that target KCNK4

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for KCNK4 Gene

Localization for KCNK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNK4 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KCNK4 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for KCNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane ISS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0034705 potassium channel complex IDA 22282805
genes like me logo Genes that share ontologies with KCNK4: view

Pathways & Interactions for KCNK4 Gene

genes like me logo Genes that share pathways with KCNK4: view

Gene Ontology (GO) - Biological Process for KCNK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport TAS 10767409
GO:0007613 memory IEA --
GO:0019233 sensory perception of pain ISS --
genes like me logo Genes that share ontologies with KCNK4: view

No data available for SIGNOR curated interactions for KCNK4 Gene

Drugs & Compounds for KCNK4 Gene

(6) Drugs for KCNK4 Gene - From: DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Riluzole Approved, Investigational Pharma Activator, blocker Sodium channel protein inhibitor 65
arachidonic acid Experimental Nutra Activator 30
BL 1249 Pharma Putative activator of potassium TREK-1, Putative K2P2.1 (TREK-1) channel opener 0
DMP 543 Pharma K+ channel blocker and potent ACh release enhancer 0
ML365 Pharma Potent and selective TASK-1 channel blocker 0

(2) Additional Compounds for KCNK4 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
PK-THPP
1332454-07-5
Spadin
1270083-24-3

(5) Tocris Compounds for KCNK4 Gene

Compound Action Cas Number
BL 1249 Putative K2P2.1 (TREK-1) channel opener 18200-13-0
DMP 543 K+ channel blocker and potent ACh release enhancer 160588-45-4
ML 365 Potent and selective TASK-1 channel blocker 947914-18-3
PK-THPP Potent TASK-3 channel blocker 1332454-07-5
Spadin Potent TREK-1 channel blocker 1270083-24-3
genes like me logo Genes that share compounds with KCNK4: view

Transcripts for KCNK4 Gene

Unigene Clusters for KCNK4 Gene

Potassium channel, subfamily K, member 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for KCNK4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c · 2d · 2e ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10a · 10b · 10c · 10d ^ 11a · 11b ^
SP1: - - - - -
SP2: - - - - - - - -
SP3: - - - - - - -
SP4: - -
SP5: -
SP6: - - - - - -
SP7: - -
SP8: - - - - - - - - - - - -
SP9: - - - - - - - - -
SP10:
SP11: - - - -

ExUns: 12 ^ 13 ^ 14
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for KCNK4 Gene

GeneLoc Exon Structure for
KCNK4
ECgene alternative splicing isoforms for
KCNK4

Expression for KCNK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for KCNK4 Gene

mRNA differential expression in normal tissues according to GTEx for KCNK4 Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x6.4), Brain - Amygdala (x6.1), Brain - Hippocampus (x6.1), Brain - Cortex (x6.0), Brain - Anterior cingulate cortex (BA24) (x5.4), Brain - Caudate (basal ganglia) (x4.9), Brain - Frontal Cortex (BA9) (x4.8), and Brain - Putamen (basal ganglia) (x4.7).

Protein differential expression in normal tissues from HIPED for KCNK4 Gene

This gene is overexpressed in Urine (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for KCNK4 Gene



Protein tissue co-expression partners for KCNK4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of KCNK4 Gene:

KCNK4

SOURCE GeneReport for Unigene cluster for KCNK4 Gene:

Hs.647233

Evidence on tissue expression from TISSUES for KCNK4 Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with KCNK4: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for KCNK4 Gene

Orthologs for KCNK4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KCNK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KCNK4 34 35
  • 99.58 (n)
dog
(Canis familiaris)
Mammalia KCNK4 34 35
  • 88.83 (n)
cow
(Bos Taurus)
Mammalia KCNK4 34 35
  • 88.35 (n)
mouse
(Mus musculus)
Mammalia Kcnk4 34 16 35
  • 81.51 (n)
rat
(Rattus norvegicus)
Mammalia Kcnk4 34
  • 80.7 (n)
oppossum
(Monodelphis domestica)
Mammalia KCNK4 35
  • 38 (a)
OneToOne
chicken
(Gallus gallus)
Aves -- 35
  • 32 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 35 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia kcnk4 34
  • 60.14 (n)
zebrafish
(Danio rerio)
Actinopterygii BX465841.1 35
  • 36 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6929 35
  • 32 (a)
ManyToMany
-- 35
  • 28 (a)
ManyToMany
Species where no ortholog for KCNK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for KCNK4 Gene

ENSEMBL:
Gene Tree for KCNK4 (if available)
TreeFam:
Gene Tree for KCNK4 (if available)

Paralogs for KCNK4 Gene

Paralogs for KCNK4 Gene

(6) SIMAP similar genes for KCNK4 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with KCNK4: view

Variants for KCNK4 Gene

Sequence variations from dbSNP and Humsavar for KCNK4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs1000079532 -- 64,293,184(+) GCGAC(A/C)AGGAG intron-variant, nc-transcript-variant, reference, missense
rs1000451236 -- 64,293,623(+) TGAGA(C/T)GGAGT intron-variant
rs1000676012 -- 64,292,303(+) ACCCC(C/G)GCCCC intron-variant
rs1000811738 -- 64,292,137(+) GCGGG(A/G)CGGCG intron-variant
rs1001526080 -- 64,294,355(+) TCTAC(C/T)AAAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for KCNK4 Gene

Variant ID Type Subtype PubMed ID
dgv1963n54 CNV loss 21841781
esv3626658 CNV loss 21293372
nsv357 CNV insertion 18451855
nsv469961 CNV loss 18288195
nsv832186 CNV loss 17160897
nsv951010 CNV deletion 24416366

Variation tolerance for KCNK4 Gene

Residual Variation Intolerance Score: 51.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.94; 83.93% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for KCNK4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
KCNK4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KCNK4 Gene

Disorders for KCNK4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for KCNK4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
dentin sensitivity
  • sensitive dentin
- elite association - COSMIC cancer census association via MalaCards
Search KCNK4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for KCNK4

Genetic Association Database (GAD)
KCNK4
Human Genome Epidemiology (HuGE) Navigator
KCNK4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
KCNK4
genes like me logo Genes that share disorders with KCNK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KCNK4 Gene

Publications for KCNK4 Gene

  1. Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two- pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression. (PMID: 12191490) Ozaita A. … Vega-Saenz de Miera E. (Brain Res. Mol. Brain Res. 2002) 3 4 22 64
  2. Cloning and expression of human TRAAK, a polyunsaturated fatty acids- activated and mechano-sensitive K(+) channel. (PMID: 10767409) Lesage F. … Lazdunski M. (FEBS Lett. 2000) 2 3 4 64
  3. Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels. (PMID: 25500157) Lolicato M. … Minor D.L. Jr. (Neuron 2014) 3 4 64
  4. Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel. (PMID: 23341632) Brohawn S.G. … MacKinnon R. (Proc. Natl. Acad. Sci. U.S.A. 2013) 3 4 64
  5. Crystal structure of the human K2P TRAAK, a lipid- and mechano- sensitive K+ ion channel. (PMID: 22282805) Brohawn S.G. … MacKinnon R. (Science 2012) 3 4 64

Products for KCNK4 Gene

Sources for KCNK4 Gene

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