Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion condu... See more...

Aliases for KCNJ4 Gene

Aliases for KCNJ4 Gene

  • Potassium Inwardly Rectifying Channel Subfamily J Member 4 2 3 5
  • HIRK2 2 3 4
  • HRK1 2 3 4
  • IRK3 2 3 4
  • HIR 2 3 4
  • Inward Rectifier Potassium Channel 4 3 4
  • Inward Rectifier K(+) Channel Kir2.3 3 4
  • Kir2.3 2 3
  • IRK-3 3 4
  • Potassium Inwardly-Rectifying Channel, Subfamily J, Member 4 2
  • Potassium Channel, Inwardly Rectifying Subfamily J, Member 4 3
  • Potassium Channel, Inwardly Rectifying Subfamily J Member 4 4
  • Potassium Voltage-Gated Channel Subfamily J Member 4 3
  • Hippocampal Inward Rectifier Potassium Channel 3
  • Hippocampal Inward Rectifier 4
  • KCNJ4 5

External Ids for KCNJ4 Gene

Previous GeneCards Identifiers for KCNJ4 Gene

  • GC22M035436
  • GC22M037065
  • GC22M037146
  • GC22M038822
  • GC22M021788

Summaries for KCNJ4 Gene

Entrez Gene Summary for KCNJ4 Gene

  • Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for KCNJ4 Gene

KCNJ4 (Potassium Inwardly Rectifying Channel Subfamily J Member 4) is a Protein Coding gene. Diseases associated with KCNJ4 include Andersen Cardiodysrhythmic Periodic Paralysis and Seizures, Sensorineural Deafness, Ataxia, Mental Retardation, And Electrolyte Imbalance. Among its related pathways are Inwardly rectifying K+ channels and Transmission across Chemical Synapses. Gene Ontology (GO) annotations related to this gene include PDZ domain binding and inward rectifier potassium channel activity. An important paralog of this gene is KCNJ12.

UniProtKB/Swiss-Prot Summary for KCNJ4 Gene

  • Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity).

Tocris Summary for KCNJ4 Gene

  • The inward-rectifier potassium channel family (also known as 2-TM channels) include the strong inward-rectifier channels (Kir2.x), the G-protein-activated inward-rectifier channels (Kir3.x) and the ATP-sensitive channels (Kir6.x), which combine with sulphonylurea receptors.

Gene Wiki entry for KCNJ4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KCNJ4 Gene

Genomics for KCNJ4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KCNJ4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KCNJ4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KCNJ4

Top Transcription factor binding sites by QIAGEN in the KCNJ4 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • c-Myc
  • Max1

Genomic Locations for KCNJ4 Gene

Genomic Locations for KCNJ4 Gene
chr22:38,426,327-38,455,199
(GRCh38/hg38)
Size:
28,873 bases
Orientation:
Minus strand
chr22:38,822,332-38,851,205
(GRCh37/hg19)
Size:
28,874 bases
Orientation:
Minus strand

Genomic View for KCNJ4 Gene

Genes around KCNJ4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KCNJ4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KCNJ4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KCNJ4 Gene

Proteins for KCNJ4 Gene

  • Protein details for KCNJ4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48050-KCNJ4_HUMAN
    Recommended name:
    Inward rectifier potassium channel 4
    Protein Accession:
    P48050
    Secondary Accessions:
    • Q14D44

    Protein attributes for KCNJ4 Gene

    Size:
    445 amino acids
    Molecular mass:
    49500 Da
    Quaternary structure:
    • Homomultimeric and heteromultimeric association with KCNJ2 and KCNJ12. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking (By similarity). Interacts with TAX1BP3. TAX1BP3 competes with LIN7 family members for KCNJ4 binding.

    Three dimensional structures from OCA and Proteopedia for KCNJ4 Gene

neXtProt entry for KCNJ4 Gene

Post-translational modifications for KCNJ4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for KCNJ4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KCNJ4 Gene

Domains & Families for KCNJ4 Gene

Gene Families for KCNJ4 Gene

Protein Domains for KCNJ4 Gene

InterPro:
Blocks:
  • Inward rectifier K+ channel superfamily signature
  • Kir2.3 inward rectifier K+ channel signature
ProtoNet:

Suggested Antigen Peptide Sequences for KCNJ4 Gene

GenScript: Design optimal peptide antigens:
  • Potassium channel, inwardly rectifying subfamily J member 4 (IRK4_HUMAN)
  • KCNJ4 protein (Q58F07_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P48050

UniProtKB/Swiss-Prot:

KCNJ4_HUMAN :
  • The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties.
  • Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ4 subfamily.
Domain:
  • The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties.
Family:
  • Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ4 subfamily.
genes like me logo Genes that share domains with KCNJ4: view

Function for KCNJ4 Gene

Molecular function for KCNJ4 Gene

UniProtKB/Swiss-Prot Function:
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity).
GENATLAS Biochemistry:
potassium non voltage-gated channel,inwardly rectifying,expressed in heart

Phenotypes From GWAS Catalog for KCNJ4 Gene

Gene Ontology (GO) - Molecular Function for KCNJ4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005242 inward rectifier potassium channel activity TAS,IBA 21873635
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005515 protein binding IPI 16855024
GO:0030165 PDZ domain binding IPI 16855024
genes like me logo Genes that share ontologies with KCNJ4: view
genes like me logo Genes that share phenotypes with KCNJ4: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNJ4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KCNJ4 Gene

Localization for KCNJ4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNJ4 Gene

Cell membrane. Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane. Multi-pass membrane protein. Cytoplasmic vesicle membrane. Note=TAX1BP3 binding promotes dissociation of KCNJ4 from LIN7 famaly members and KCNJ4 internalization. {ECO:0000250}.

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 KCNJ4 gene
Compartment Confidence
plasma membrane 5
extracellular 2
endoplasmic reticulum 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endosome 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for KCNJ4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0008076 voltage-gated potassium channel complex TAS 8051145
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0016323 basolateral plasma membrane IDA 16855024
genes like me logo Genes that share ontologies with KCNJ4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KCNJ4 Gene

Pathways & Interactions for KCNJ4 Gene

genes like me logo Genes that share pathways with KCNJ4: view

Pathways by source for KCNJ4 Gene

2 KEGG pathways for KCNJ4 Gene
1 Qiagen pathway for KCNJ4 Gene
  • Dopamine-DARPP32 Feedback onto cAMP Pathway

Gene Ontology (GO) - Biological Process for KCNJ4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport TAS 8051145
GO:0034220 ion transmembrane transport IEA --
GO:0034765 regulation of ion transmembrane transport IBA 21873635
GO:0061337 cardiac conduction TAS --
genes like me logo Genes that share ontologies with KCNJ4: view

No data available for SIGNOR curated interactions for KCNJ4 Gene

Drugs & Compounds for KCNJ4 Gene

(26) Drugs for KCNJ4 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Carvedilol Approved, Investigational Pharma Antagonist, Target, inhibitor 199
Dronedarone Approved Pharma Target, inhibitor 34
Ranolazine Approved, Investigational Pharma Target, inhibitor 85
Magnesium Approved, Experimental, Investigational Pharma 0
Glyburide Approved Pharma Channel blocker, Inhibitor, Inhibition Kir6 (KATP) channel blocker 127

(4) Additional Compounds for KCNJ4 Gene - From: IUPHAR and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
H<sup>+</sup> (extracellular)
Activator, Allosteric regulator, Inhibition, Gating inhibitor, Antagonist, Channel blocker, Potentiation
H<sup>+</sup> (intracellular)
Gating inhibitor, Antagonist

(5) Tocris Compounds for KCNJ4 Gene

Compound Action Cas Number
Glibenclamide Kir6 (KATP) channel blocker 10238-21-8
Minoxidil Kir6 channel (KATP) opener 38304-91-5
Nicorandil Kir6 (KATP) channel opener and NO donor 65141-46-0
P1075 Potent Kir6 (KATP) channel opener 60559-98-0
ZM 226600 Kir6 (KATP) channel opener 147695-92-9

(1) ApexBio Compounds for KCNJ4 Gene

Compound Action Cas Number
Cesium chloride Potassium channel blocker 7647-17-8
genes like me logo Genes that share compounds with KCNJ4: view

Drug Products

Transcripts for KCNJ4 Gene

mRNA/cDNA for KCNJ4 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNJ4

Alternative Splicing Database (ASD) splice patterns (SP) for KCNJ4 Gene

No ASD Table

Relevant External Links for KCNJ4 Gene

GeneLoc Exon Structure for
KCNJ4

Expression for KCNJ4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KCNJ4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KCNJ4 Gene

This gene is overexpressed in Brain - Cortex (x9.2), Brain - Frontal Cortex (BA9) (x7.7), Brain - Anterior cingulate cortex (BA24) (x5.9), Brain - Putamen (basal ganglia) (x5.2), and Brain - Nucleus accumbens (basal ganglia) (x5.0).

Protein differential expression in normal tissues from HIPED for KCNJ4 Gene

This gene is overexpressed in Frontal cortex (53.8) and Fetal heart (15.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KCNJ4 Gene



Protein tissue co-expression partners for KCNJ4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KCNJ4

SOURCE GeneReport for Unigene cluster for KCNJ4 Gene:

Hs.32505

mRNA Expression by UniProt/SwissProt for KCNJ4 Gene:

P48050-KCNJ4_HUMAN
Tissue specificity: Heart, skeletal muscle, and several different brain regions including the hippocampus.

Evidence on tissue expression from TISSUES for KCNJ4 Gene

  • Nervous system(4.6)
  • Muscle(2.6)
  • Heart(2.6)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with KCNJ4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for KCNJ4 Gene

Orthologs for KCNJ4 Gene

This gene was present in the common ancestor of animals.

Orthologs for KCNJ4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KCNJ4 30 31
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KCNJ4 30 31
  • 94.08 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia KCNJ4 31
  • 93 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KCNJ4 31
  • 91 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Kcnj4 30
  • 90.34 (n)
Mouse
(Mus musculus)
Mammalia Kcnj4 30 17 31
  • 89.56 (n)
OneToOne
Chicken
(Gallus gallus)
Aves CKIR2.3 31
  • 84 (a)
OneToOne
KCNJ4 30
  • 80.97 (n)
Lizard
(Anolis carolinensis)
Reptilia KCNJ4 31
  • 79 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia kcnj4 30
  • 71.55 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC100331864 30
  • 66.67 (n)
KCNJ4 31
  • 59 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Ir 32
  • 51 (a)
Irk2 32
  • 49 (a)
Irk3 32
  • 34 (a)
Worm
(Caenorhabditis elegans)
Secernentea irk-2 31 32
  • 39 (a)
ManyToMany
irk-1 31 32
  • 32 (a)
ManyToMany
Species where no ortholog for KCNJ4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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)

Evolution for KCNJ4 Gene

ENSEMBL:
Gene Tree for KCNJ4 (if available)
TreeFam:
Gene Tree for KCNJ4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KCNJ4: view image

Paralogs for KCNJ4 Gene

(16) SIMAP similar genes for KCNJ4 Gene using alignment to 2 proteins:

  • IRK4_HUMAN
  • Q58F07_HUMAN
genes like me logo Genes that share paralogs with KCNJ4: view

Variants for KCNJ4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KCNJ4 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
rs193920820 Uncertain Significance: Malignant tumor of prostate 38,427,547(-) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for KCNJ4 Gene

Structural Variations from Database of Genomic Variants (DGV) for KCNJ4 Gene

Variant ID Type Subtype PubMed ID
esv3647730 CNV loss 21293372
esv3647731 CNV loss 21293372
esv3647732 CNV gain 21293372
nsv1058338 CNV gain 25217958
nsv1060077 CNV gain 25217958
nsv817994 CNV gain 17921354
nsv819157 CNV gain 19587683
nsv834195 CNV loss 17160897

Variation tolerance for KCNJ4 Gene

Residual Variation Intolerance Score: 6.97% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.17; 3.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KCNJ4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
KCNJ4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KCNJ4 Gene

Disorders for KCNJ4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for KCNJ4 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search KCNJ4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KCNJ4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with KCNJ4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KCNJ4 Gene

Publications for KCNJ4 Gene

  1. Primary structure and characterization of a small-conductance inwardly rectifying potassium channel from human hippocampus. (PMID: 8016146) Périer F … Vandenberg CA (Proceedings of the National Academy of Sciences of the United States of America 1994) 2 3 4 23
  2. L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. (PMID: 20424473) Yokoyama K … Hosoya T (Nephron. Clinical practice 2010) 3 41
  3. Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1. (PMID: 19635485) Yan X … Long J (Journal of molecular biology 2009) 3 4
  4. Novel insights into the structural basis of pH-sensitivity in inward rectifier K+ channels Kir2.3. (PMID: 18453743) Ureche ON … Seebohm G (Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2008) 3 23
  5. Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. (PMID: 15958527) Fang Y … Levitan I (American journal of physiology. Cell physiology 2005) 3 23

Products for KCNJ4 Gene

Sources for KCNJ4 Gene