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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 Hepatic ABC Transporters and Activation of cAMP-Dependent PKA. Gene Ontology (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

Additional gene information 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

GeneHancer (GH) Regulatory Elements for KCNK4 Gene

Promoters and enhancers for KCNK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J064290 Promoter/Enhancer 1.1 EPDnew Ensembl 650.7 +0.9 856 2.6 CTCF MXI1 SUZ12 DPF2 SP1 ZFHX2 POLR2A ZNF24 BCL6 ZBTB26 ENSG00000257069 KCNK4 CATSPERZ TRMT112 GC11P064297
GH11J064205 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 11.5 -83.7 -83707 4.4 HDGF PKNOX1 SMAD1 ARNT YY1 POLR2B ZNF766 ZNF143 ZNF592 SMARCA4 FERMT3 TRPT1 ZFPL1 PLCB3 SF1 TRMT112 ENSG00000257086 GPR137 BAD ENSG00000257069
GH11J064267 Promoter/Enhancer 1.8 Ensembl ENCODE dbSUPER 12.9 -20.6 -20602 7.2 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 MCM3 SP3 NFYC GPR137 ZFPL1 SF1 POLA2 PLCB3 ENSG00000257086 TRMT112 DNAJC4 FAU LOC102723878
GH11J064347 Promoter/Enhancer 1.3 EPDnew ENCODE 11.5 +57.1 57079 1.9 BCOR ZNF768 KLF1 JUN MAX ZMYM3 CEBPG POLR2A FOXK2 PATZ1 CCDC88B LOC102723878 MIR1237 TRMT112 PRDX5 ESRRA CATSPERZ ENSG00000207024 ENSG00000257069 KCNK4
GH11J064320 Enhancer 1 Ensembl ENCODE dbSUPER 12.2 +31.8 31818 5.3 MTA2 ZBTB2 CBFA2T3 NFXL1 DPF2 ZIC2 ZKSCAN1 EGR1 POLR2A HDAC2 PLCB3 LOC102723878 CATSPERZ ENSG00000207024 ENSG00000257069 KCNK4 BAD GPR137 ENSG00000257086 TRMT112
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KCNK4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the KCNK4 gene promoter:
  • CREB
  • c-Jun
  • deltaCREB
  • ATF-2

Genomic Locations for KCNK4 Gene

Genomic Locations for KCNK4 Gene
chr11:64,291,302-64,300,031
(GRCh38/hg38)
Size:
8,730 bases
Orientation:
Plus strand
chr11:64,058,774-64,067,503
(GRCh37/hg19)
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

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Voltage-gated ion channels

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 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).
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by arachidonic acid.

Phenotypes From GWAS Catalog for KCNK4 Gene

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:0022841 potassium ion leak channel activity IBA --
GO:0097604 temperature-gated cation channel activity ISS --
GO:0098782 mechanosensitived 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

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNK4

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

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KCNK4 Gene

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:0006811 ion transport IEA --
GO:0006813 potassium ion transport TAS 10767409
GO:0007613 memory IEA --
GO:0019233 sensory perception of pain ISS --
GO:0030322 stabilization of membrane potential IBA --
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

(5) 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 69
arachidonic acid Experimental Nutra Activator, Inhibitor, Agonist, Activation, Potentiation 33
Cesium chloride Pharma Potassium channel blocker, Potassium channel blocker; neuroprotective 0
YS-035 hydrochloride Pharma Inhibits K+ outward/pacemaker current 0

(2) Tocris Compounds for KCNK4 Gene

Compound Action Cas Number
Cesium chloride Potassium channel blocker; neuroprotective 7647-17-8
YS-035 hydrochloride Inhibits K+ outward/pacemaker current 89805-39-0
genes like me logo Genes that share compounds with KCNK4: view

Transcripts for KCNK4 Gene

mRNA/cDNA for KCNK4 Gene

Unigene Clusters for KCNK4 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNK4

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 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

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 33
  • 99.58 (n)
OneToOne
dog
(Canis familiaris)
Mammalia KCNK4 34 33
  • 88.83 (n)
OneToOne
cow
(Bos Taurus)
Mammalia KCNK4 34 33
  • 88.35 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Kcnk4 16 34 33
  • 81.51 (n)
rat
(Rattus norvegicus)
Mammalia Kcnk4 33
  • 80.7 (n)
oppossum
(Monodelphis domestica)
Mammalia KCNK4 34
  • 38 (a)
OneToOne
chicken
(Gallus gallus)
Aves -- 34
  • 32 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 35 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia kcnk4 33
  • 60.14 (n)
zebrafish
(Danio rerio)
Actinopterygii BX465841.1 34
  • 36 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6929 34
  • 32 (a)
ManyToMany
-- 34
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for KCNK4: view image

Paralogs for KCNK4 Gene

Paralogs for KCNK4 Gene

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

  • KCNK4_HUMAN
  • A3KMH3_HUMAN
  • F5GYE0_HUMAN
  • F5GZ20_HUMAN
  • Q2YDA1_HUMAN
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 Variation AA Info Type
rs1000079532 -- 64,293,184(+) C/A coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs1000451236 -- 64,293,623(+) C/T intron_variant
rs1000676012 -- 64,292,303(+) C/G intron_variant
rs1000811738 -- 64,292,137(+) G/A intron_variant
rs1001526080 -- 64,294,355(+) T/C 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)

Additional Variant Information for KCNK4 Gene

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

SNP Genotyping and Copy Number Assay Products

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

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

Additional Disease Information for KCNK4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 research. Molecular brain research 2002) 3 4 22 58
  2. Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel. (PMID: 10767409) Lesage F … Lazdunski M (FEBS letters 2000) 2 3 4 58
  3. Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels. (PMID: 25500157) Lolicato M … Minor DL (Neuron 2014) 3 4 58
  4. Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel. (PMID: 23341632) Brohawn SG … MacKinnon R (Proceedings of the National Academy of Sciences of the United States of America 2013) 3 4 58
  5. Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel. (PMID: 22282805) Brohawn SG … MacKinnon R (Science (New York, N.Y.) 2012) 3 4 58

Products for KCNK4 Gene

Sources for KCNK4 Gene

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