Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of... See more...

Aliases for KCNE4 Gene

Aliases for KCNE4 Gene

  • Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4 2 3 5
  • Potassium Channel, Voltage Gated Subfamily E Regulatory Beta Subunit 4 2 3
  • Potassium Voltage-Gated Channel, Isk-Related Family, Member 4 2 3
  • Potassium Voltage-Gated Channel Subfamily E Member 4 3 4
  • Minimum Potassium Ion Channel-Related Peptide 3 3 4
  • Potassium Channel Subunit Beta MiRP3 3 4
  • Cardiac Voltage-Gated Potassium Channel Accessory Subunit 4 3
  • MINK-Related Peptide 3 3
  • MinK-Related Peptide 3 4
  • MIRP3 3
  • KCNE4 5
  • MiRP3 2

External Ids for KCNE4 Gene

Previous GeneCards Identifiers for KCNE4 Gene

  • GC02P221939
  • GC02P222637
  • GC02P223880
  • GC02P224119
  • GC02P223742
  • GC02P223625
  • GC02P215768

Summaries for KCNE4 Gene

Entrez Gene Summary for KCNE4 Gene

  • Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a type I membrane protein, and a beta subunit that assembles with a potassium channel alpha-subunit to modulate the gating kinetics and enhance stability of the multimeric complex. This gene is prominently expressed in the embryo and in adult uterus. [provided by RefSeq, Jul 2008]

GeneCards Summary for KCNE4 Gene

KCNE4 (Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 4) is a Protein Coding gene. Diseases associated with KCNE4 include Cataract 31, Multiple Types and Deafness, Autosomal Recessive 98. Among its related pathways are Antiarrhythmic Pathway, Pharmacodynamics and Dopamine-DARPP32 Feedback onto cAMP Pathway. Gene Ontology (GO) annotations related to this gene include voltage-gated potassium channel activity.

UniProtKB/Swiss-Prot Summary for KCNE4 Gene

  • Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. May associate with KCNQ1/KVLTQ1 and inhibit potassium current.

Tocris Summary for KCNE4 Gene

  • Voltage-gated potassium channels (KV) belong to the 6-TM family of potassium channel that also comprises the Ca2+-activated Slo (actually 7-TM) and the Ca2+-activated SK subfamilies. The alpha-subunits contain a single pore-forming region and combine to form tetramers.

Gene Wiki entry for KCNE4 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KCNE4 Gene

Genomics for KCNE4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KCNE4 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
GH02J223050 Promoter/Enhancer 1.6 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 8.7 +2.7 2688 7.6 NFATC3 TAL1 RXRA ZFP91 ZNF316 JUND PRDM10 EHMT2 ZBTB33 TCF12 HSALNG0022569 ACSL3-AS1 ACSL3 KCNE4 MRPL44 SCG2
GH02J223099 Enhancer 1 Ensembl ENCODE dbSUPER 11.1 +49.1 49104 3 CTCF REST SMC3 RAD21 EP400 ZNF652 ZNF148 ESRRA L3MBTL2 SP1 HSALNG0022572 KCNE4 HSALNG0022571 SCG2
GH02J223026 Enhancer 0.8 Ensembl ENCODE 12.1 -24.8 -24754 1.7 CUX1 FOXA2 MAFF ZNF316 NFE2 NFE2L2 MAFK FOXA1 JUND MAFG HSALNG0022564 KCNE4 HSALNG0022568 ACSL3
GH02J223009 Enhancer 0.5 Ensembl ENCODE 10.8 -41.3 -41252 1.9 CEBPB FOS KCNE4 piR-61289-040 HSALNG0022564 HSALNG0022565 ACSL3
GH02J223723 Enhancer 1.1 ENCODE CraniofacialAtlas 5.1 +674.0 673982 4 TBP MNT IKZF1 SMAD5 CTCF BRCA1 CEBPB SIN3A REST NFATC3 HSALNG0022600 lnc-AP1S3-1 piR-57845-007 KCNE4 HSALNG0022599 AP1S3 SCG2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KCNE4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KCNE4

Top Transcription factor binding sites by QIAGEN in the KCNE4 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • GR
  • GR-alpha
  • GR-beta
  • Nkx3-1 v4

Genomic Locations for KCNE4 Gene

Latest Assembly
chr2:223,051,814-223,198,399
(GRCh38/hg38)
Size:
146,586 bases
Orientation:
Plus strand

Previous Assembly
chr2:223,916,908-223,920,355
(GRCh37/hg19 by Entrez Gene)
Size:
3,448 bases
Orientation:
Plus strand

chr2:223,916,532-224,063,117
(GRCh37/hg19 by Ensembl)
Size:
146,586 bases
Orientation:
Plus strand

Genomic View for KCNE4 Gene

Genes around KCNE4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KCNE4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KCNE4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KCNE4 Gene

Proteins for KCNE4 Gene

  • Protein details for KCNE4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WWG9-KCNE4_HUMAN
    Recommended name:
    Potassium voltage-gated channel subfamily E member 4
    Protein Accession:
    Q8WWG9
    Secondary Accessions:
    • B7Z275
    • Q53SM4
    • Q96CC4

    Protein attributes for KCNE4 Gene

    Size:
    221 amino acids
    Molecular mass:
    23806 Da
    Quaternary structure:
    • Interacts with KCNQ1; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity.
    SequenceCaution:
    • Sequence=AAH14429.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL49979.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

neXtProt entry for KCNE4 Gene

Post-translational modifications for KCNE4 Gene

  • Glycosylation at Asn9
  • Modification sites at PhosphoSitePlus

Other Protein References for KCNE4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KCNE4 Gene

Domains & Families for KCNE4 Gene

Gene Families for KCNE4 Gene

Protein Domains for KCNE4 Gene

InterPro:
Blocks:
  • KCNE voltage-gated K+ channel beta subunit family signature
ProtoNet:

Suggested Antigen Peptide Sequences for KCNE4 Gene

GenScript: Design optimal peptide antigens:
  • Potassium voltage-gated channel subfamily E member (A5H1P5_HUMAN)
  • Potassium channel subunit beta MiRP3 (KCNE4_HUMAN)
  • Potassium voltage-gated channel subfamily E member (Q2N1I0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8WWG9

UniProtKB/Swiss-Prot:

KCNE4_HUMAN :
  • Belongs to the potassium channel KCNE family.
Family:
  • Belongs to the potassium channel KCNE family.
genes like me logo Genes that share domains with KCNE4: view

Function for KCNE4 Gene

Molecular function for KCNE4 Gene

UniProtKB/Swiss-Prot Function:
Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. May associate with KCNQ1/KVLTQ1 and inhibit potassium current.

Phenotypes From GWAS Catalog for KCNE4 Gene

Gene Ontology (GO) - Molecular Function for KCNE4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005249 voltage-gated potassium channel activity IEA --
GO:0005251 contributes_to delayed rectifier potassium channel activity IBA 21873635
GO:0005267 potassium channel activity IEA --
GO:0005515 protein binding IPI 19687231
genes like me logo Genes that share ontologies with KCNE4: view
genes like me logo Genes that share phenotypes with KCNE4: view

Animal Models for research

  • Taconic Biosciences Mouse Models for KCNE4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNE4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KCNE4 Gene

Localization for KCNE4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNE4 Gene

Membrane. Single-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 KCNE4 gene
Compartment Confidence
plasma membrane 3
extracellular 2
nucleus 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubules (2)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KCNE4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008076 colocalizes_with voltage-gated potassium channel complex IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0016324 apical plasma membrane IEA --
genes like me logo Genes that share ontologies with KCNE4: view

Pathways & Interactions for KCNE4 Gene

genes like me logo Genes that share pathways with KCNE4: view

Pathways by source for KCNE4 Gene

1 Qiagen pathway for KCNE4 Gene
  • Dopamine-DARPP32 Feedback onto cAMP Pathway

Gene Ontology (GO) - Biological Process for KCNE4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0034765 regulation of ion transmembrane transport IEA --
GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization IBA 21873635
GO:0071805 potassium ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with KCNE4: view

No data available for SIGNOR curated interactions for KCNE4 Gene

Drugs & Compounds for KCNE4 Gene

(6) Drugs for KCNE4 Gene - From: DrugBank and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Enflurane Approved, Investigational, Vet_approved Pharma Target, inhibitor, activator 2
Miconazole Approved, Investigational, Vet_approved Pharma Target, inhibitor 3138
Promethazine Approved, Investigational Pharma Target, inducer 492
Chromanol 293B Pharma IKs blocker. Also blocks ICFTR 0
Flupirtine maleate Pharma KV7 channel activator 0

(1) Additional Compounds for KCNE4 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Kaliotoxin
145199-73-1

(4) Tocris Compounds for KCNE4 Gene

Compound Action Cas Number
Chromanol 293B IKs blocker. Also blocks ICFTR 163163-23-3
Flupirtine maleate KV7 channel activator 75507-68-5
Kaliotoxin KV and KCa blocker 145199-73-1
MaxiPost Potassium channel modulator; exerts subtype-specific effects 187523-35-9
genes like me logo Genes that share compounds with KCNE4: view

Transcripts for KCNE4 Gene

mRNA/cDNA for KCNE4 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNE4

Alternative Splicing Database (ASD) splice patterns (SP) for KCNE4 Gene

No ASD Table

Relevant External Links for KCNE4 Gene

GeneLoc Exon Structure for
KCNE4

Expression for KCNE4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KCNE4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KCNE4 Gene

This gene is overexpressed in Artery - Tibial (x4.4).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KCNE4

SOURCE GeneReport for Unigene cluster for KCNE4 Gene:

Hs.348522

mRNA Expression by UniProt/SwissProt for KCNE4 Gene:

Q8WWG9-KCNE4_HUMAN
Tissue specificity: Predominantly expressed in embryo and adult uterus. Low expression found in kidney, small intestine, lung and heart.

Evidence on tissue expression from TISSUES for KCNE4 Gene

  • Heart(4.4)
  • Nervous system(4.4)
  • Kidney(4.3)
  • Lung(4.1)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with KCNE4: view

Primer products for research

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for KCNE4 Gene

Orthologs for KCNE4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KCNE4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KCNE4 30 31
  • 99.1 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KCNE4 30 31
  • 88.1 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Kcne4 30
  • 87.25 (n)
Dog
(Canis familiaris)
Mammalia KCNE4 30 31
  • 87.18 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Kcne4 30 17 31
  • 86.67 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia KCNE4 31
  • 75 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KCNE4 31
  • 72 (a)
OneToOne
Chicken
(Gallus gallus)
Aves KCNE4 30 31
  • 72.6 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia KCNE4 31
  • 60 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia kcne4 30
  • 55.63 (n)
Zebrafish
(Danio rerio)
Actinopterygii kcne4 30 31
  • 56.62 (n)
OneToOne
Species where no ortholog for KCNE4 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)
  • 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)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for KCNE4 Gene

ENSEMBL:
Gene Tree for KCNE4 (if available)
TreeFam:
Gene Tree for KCNE4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KCNE4: view image

Paralogs for KCNE4 Gene

(1) SIMAP similar genes for KCNE4 Gene using alignment to 3 proteins:

  • KCNE4_HUMAN
  • A5H1P5_HUMAN
  • Q2N1I0_HUMAN
genes like me logo Genes that share paralogs with KCNE4: view

No data available for Paralogs for KCNE4 Gene

Variants for KCNE4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KCNE4 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs12621643 - p.Asp196Glu
rs13409084 - p.Gly98Ser

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for KCNE4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for KCNE4 Gene

Residual Variation Intolerance Score: 47% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.05; 21.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KCNE4 Gene

Human Gene Mutation Database (HGMD)
KCNE4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KCNE4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for KCNE4 Gene

Disorders for KCNE4 Gene

MalaCards: The human disease database

(8) MalaCards diseases for KCNE4 Gene - From: COP

- elite association - COSMIC cancer census association via MalaCards
Search KCNE4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KCNE4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with KCNE4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KCNE4 Gene

Publications for KCNE4 Gene

  1. Distinct subdomains of the KCNQ1 S6 segment determine channel modulation by different KCNE subunits. (PMID: 19687231) Vanoye CG … George AL (The Journal of general physiology 2009) 3 4 23
  2. Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women. (PMID: 20966902) Croteau-Chonka DC … Mohlke KL (Obesity (Silver Spring, Md.) 2011) 3 41
  3. Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting. (PMID: 20533308) Roura-Ferrer M … Felipe A (Journal of cellular physiology 2010) 3 4
  4. Germline genomic variants associated with childhood acute lymphoblastic leukemia. (PMID: 19684603) Treviño LR … Relling MV (Nature genetics 2009) 3 41
  5. KCNE4 suppresses Kv1.3 currents by modulating trafficking, surface expression and channel gating. (PMID: 19773357) Solé L … Felipe A (Journal of cell science 2009) 3 23

Products for KCNE4 Gene

Sources for KCNE4 Gene