The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcrip... See more...

Aliases for KCNH3 Gene

Aliases for KCNH3 Gene

  • Potassium Voltage-Gated Channel Subfamily H Member 3 2 3 4 5
  • BEC1 2 3 4
  • Potassium Voltage-Gated Channel, Subfamily H (Eag-Related), Member 3 2 3
  • Voltage-Gated Potassium Channel Subunit Kv12.2 3 4
  • Ether-A-Go-Go-Like Potassium Channel 2 3 4
  • Brain-Specific Eag-Like Channel 1 3 4
  • ELK Channel 2 3 4
  • Kv12.2 2 3
  • ELK2 3 4
  • Potassium Channel, Voltage Gated Eag Related Subfamily H, Member 3 3
  • Ether-A-Go-Go K(+) Channel Family Member 3
  • KIAA1282 4
  • KCNH3 5
  • Elk2 2

External Ids for KCNH3 Gene

Previous GeneCards Identifiers for KCNH3 Gene

  • GC12P050150
  • GC12P049989
  • GC12P049649
  • GC12P048219
  • GC12P049933
  • GC12P046963

Summaries for KCNH3 Gene

Entrez Gene Summary for KCNH3 Gene

  • The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

GeneCards Summary for KCNH3 Gene

KCNH3 (Potassium Voltage-Gated Channel Subfamily H Member 3) is a Protein Coding gene. Diseases associated with KCNH3 include Deafness, Autosomal Dominant 2A and Human Immunodeficiency Virus Type 1. Among its related pathways are Potassium Channels and Transmission across Chemical Synapses. Gene Ontology (GO) annotations related to this gene include obsolete signal transducer activity and voltage-gated potassium channel activity. An important paralog of this gene is KCNH8.

UniProtKB/Swiss-Prot Summary for KCNH3 Gene

  • Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.

Tocris Summary for KCNH3 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 KCNH3 Gene

Additional gene information for KCNH3 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KCNH3 Gene

Genomics for KCNH3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KCNH3 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
GH12J049538 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 600.7 0.0 -40 3.4 ZNF512 RFX1 KDM1A ZIC2 MTA1 PATZ1 EZH2 ZNF600 ZNF341 ZNF561 ENSG00000287537 KCNH3 lnc-KCNH3-2 SPATS2 DNAJC22 ENSG00000257464
GH12J049364 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 12 -170.9 -170909 5.9 SP1 HNRNPL CTCF PRDM10 REST ZNF629 IKZF1 ZNF692 POLR2A ZNF7 SPATS2 TUBA1A KCNH3 MCRS1 DNAJC22 PRPF40B piR-32285-017
GH12J049488 Enhancer 1.2 Ensembl ENCODE dbSUPER 11 -47.8 -47840 4.2 PRDM10 ZNF629 JUND PRDM1 PATZ1 ZNF600 CTCF ZNF639 ZNF10 TSHZ1 KCNH3 MCRS1 SPATS2 C1QL4 DNAJC22 TUBA1C piR-50443-078 piR-59056-002
GH12J049501 Enhancer 1 Ensembl ENCODE dbSUPER 12.1 -33.5 -33546 7.6 PRDM1 REST CEBPB SP1 JUND ESR1 ATF3 NR3C1 ZSCAN5C OSR2 SPATS2 KCNH3 C1QL4 MCRS1 PRPH DNAJC22 ENSG00000257464 piR-50443-078 HSALNG0090948
GH12J049421 Enhancer 1.1 Ensembl ENCODE 10.9 -116.8 -116827 1.4 GATAD2A ATF7 IKZF1 RCOR2 JUND MTA2 PKNOX1 RXRB IRF2 DPF2 KCNH3 MCRS1 DNAJC22 MN297152 piR-56759-120 SPATS2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KCNH3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KCNH3

Top Transcription factor binding sites by QIAGEN in the KCNH3 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5

Genomic Locations for KCNH3 Gene

Genomic Locations for KCNH3 Gene
chr12:49,538,541-49,558,337
(GRCh38/hg38)
Size:
19,797 bases
Orientation:
Plus strand
chr12:49,932,940-49,952,091
(GRCh37/hg19)
Size:
19,152 bases
Orientation:
Plus strand

Genomic View for KCNH3 Gene

Genes around KCNH3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KCNH3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KCNH3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KCNH3 Gene

Proteins for KCNH3 Gene

  • Protein details for KCNH3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULD8-KCNH3_HUMAN
    Recommended name:
    Potassium voltage-gated channel subfamily H member 3
    Protein Accession:
    Q9ULD8
    Secondary Accessions:
    • Q9UQ06

    Protein attributes for KCNH3 Gene

    Size:
    1083 amino acids
    Molecular mass:
    117129 Da
    Quaternary structure:
    • The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
    SequenceCaution:
    • Sequence=BAA86596.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for KCNH3 Gene

Post-translational modifications for KCNH3 Gene

  • Glycosylation at Asn421, Asn428, and Asn436
  • Modification sites at PhosphoSitePlus

Other Protein References for KCNH3 Gene

No data available for DME Specific Peptides for KCNH3 Gene

Domains & Families for KCNH3 Gene

Gene Families for KCNH3 Gene

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

Protein Domains for KCNH3 Gene

InterPro:
Blocks:
  • PAS domain
  • PAC motif
  • Cyclic nucleotide-binding domain
  • EAG/ELK/ERG potassium channel family signature
  • ERG potassium channel family signature
  • ELK potassium channel family signature
ProtoNet:

Suggested Antigen Peptide Sequences for KCNH3 Gene

GenScript: Design optimal peptide antigens:
  • Potassium voltage-gated channel, subfamily H (Eag-related), member 3 (B9EK44_HUMAN)
  • Voltage-gated potassium channel subunit Kv12.2 (KCNH3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9ULD8

UniProtKB/Swiss-Prot:

KCNH3_HUMAN :
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
  • Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.2/KCNH3 sub-subfamily.
Domain:
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Family:
  • Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.2/KCNH3 sub-subfamily.
genes like me logo Genes that share domains with KCNH3: view

Function for KCNH3 Gene

Molecular function for KCNH3 Gene

UniProtKB/Swiss-Prot Function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.
GENATLAS Biochemistry:
potassium voltage-gated channel,subfamily H (eag-related),member 3,ether-a-go-go K+ channel family member,exclusively expressed in the brain,mainly in the cerebral cortex,amygdala,hippocampus and striatum

Phenotypes From GWAS Catalog for KCNH3 Gene

Gene Ontology (GO) - Molecular Function for KCNH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005249 voltage-gated potassium channel activity TAS 10455180
GO:0005267 potassium channel activity IEA --
GO:0005515 protein binding IPI 20638388
genes like me logo Genes that share ontologies with KCNH3: view
genes like me logo Genes that share phenotypes with KCNH3: view

Animal Models for KCNH3 Gene

MGI Knock Outs for KCNH3:

Animal Model Products

  • Taconic Biosciences Mouse Models for KCNH3

CRISPR Products

miRNA for KCNH3 Gene

miRTarBase miRNAs that target KCNH3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KCNH3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for KCNH3 Gene

Localization for KCNH3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KCNH3 Gene

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 KCNH3 gene
Compartment Confidence
plasma membrane 5
nucleus 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KCNH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane NAS 10455180
genes like me logo Genes that share ontologies with KCNH3: view

Pathways & Interactions for KCNH3 Gene

PathCards logo

SuperPathways for KCNH3 Gene

genes like me logo Genes that share pathways with KCNH3: view

Pathways by source for KCNH3 Gene

1 Qiagen pathway for KCNH3 Gene
  • Dopamine-DARPP32 Feedback onto cAMP Pathway

Gene Ontology (GO) - Biological Process for KCNH3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport TAS 10455180
GO:0034765 regulation of ion transmembrane transport IEA --
GO:0042391 regulation of membrane potential IBA 21873635
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with KCNH3: view

No data available for SIGNOR curated interactions for KCNH3 Gene

Drugs & Compounds for KCNH3 Gene

(7) Drugs for KCNH3 Gene - From: DrugBank, DGIdb, IUPHAR, HMDB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Enflurane Approved, Investigational, Vet_approved Pharma Target, inhibitor, activator 2
Promethazine Approved, Investigational Pharma Target, inducer 470
cyclic amp Experimental Pharma 0
Cs<sup>+</sup> Pharma Inhibitor, Pore Blocker, Antagonist 0
Chromanol 293B Pharma Pore Blocker, Antagonist IKs blocker. Also blocks ICFTR 0

(1) Additional Compounds for KCNH3 Gene - From: Tocris

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

(4) Tocris Compounds for KCNH3 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 KCNH3: view

Transcripts for KCNH3 Gene

mRNA/cDNA for KCNH3 Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
5 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 KCNH3

Alternative Splicing Database (ASD) splice patterns (SP) for KCNH3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17
SP1: -
SP2:
SP3:

Relevant External Links for KCNH3 Gene

GeneLoc Exon Structure for
KCNH3

Expression for KCNH3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KCNH3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KCNH3 Gene

This gene is overexpressed in Brain - Cortex (x9.6), Brain - Frontal Cortex (BA9) (x6.5), Brain - Anterior cingulate cortex (BA24) (x5.8), Brain - Amygdala (x4.9), and Brain - Hippocampus (x4.9).

Protein differential expression in normal tissues from HIPED for KCNH3 Gene

This gene is overexpressed in Colon (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KCNH3 Gene



Protein tissue co-expression partners for KCNH3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KCNH3

SOURCE GeneReport for Unigene cluster for KCNH3 Gene:

Hs.64064

mRNA Expression by UniProt/SwissProt for KCNH3 Gene:

Q9ULD8-KCNH3_HUMAN
Tissue specificity: Detected only in brain, in particular in the telencephalon. Detected in the cerebral cortex, occipital pole, frontal and temporal lobe, putamen, amygdala, hippocampus and caudate nucleus.

Evidence on tissue expression from TISSUES for KCNH3 Gene

  • Nervous system(4.5)
genes like me logo Genes that share expression patterns with KCNH3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for KCNH3 Gene

Orthologs for KCNH3 Gene

This gene was present in the common ancestor of animals.

Orthologs for KCNH3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KCNH3 30 31
  • 99.63 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KCNH3 30 31
  • 92.3 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KCNH3 30 31
  • 90.77 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Kcnh3 30 17 31
  • 89.6 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Kcnh3 30
  • 89.1 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 68 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia KCNH3 31
  • 68 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100492237 30
  • 61.54 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC100006614 30
  • 63.85 (n)
kcnh3 31
  • 58 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta elk 31 32
  • 33 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 48 (a)
OneToMany
Species where no ortholog for KCNH3 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)
  • Chicken (Gallus gallus)
  • 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)
  • 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)
  • Oppossum (Monodelphis domestica)
  • 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 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 KCNH3 Gene

ENSEMBL:
Gene Tree for KCNH3 (if available)
TreeFam:
Gene Tree for KCNH3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KCNH3: view image

Paralogs for KCNH3 Gene

(6) SIMAP similar genes for KCNH3 Gene using alignment to 2 proteins:

  • KCNH3_HUMAN
  • B9EK44_HUMAN
genes like me logo Genes that share paralogs with KCNH3: view

Variants for KCNH3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KCNH3 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
713125 Benign: not provided 49,544,303(+) C/T SYNONYMOUS_VARIANT
735166 Benign: not provided 49,557,497(+) C/T SYNONYMOUS_VARIANT
747981 Benign: not provided 49,544,261(+) C/T SYNONYMOUS_VARIANT
747982 Benign: not provided 49,554,328(+) T/C INTRON_VARIANT
783658 Benign: not provided 49,554,422(+) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for KCNH3 Gene

Structural Variations from Database of Genomic Variants (DGV) for KCNH3 Gene

Variant ID Type Subtype PubMed ID
nsv1118238 CNV deletion 24896259
nsv832406 CNV loss 17160897

Variation tolerance for KCNH3 Gene

Residual Variation Intolerance Score: 6.22% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.88; 74.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KCNH3 Gene

Human Gene Mutation Database (HGMD)
KCNH3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KCNH3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KCNH3 Gene

Disorders for KCNH3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for KCNH3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
deafness, autosomal dominant 2a
  • dfna2a
human immunodeficiency virus type 1
  • human immunodeficiency virus type 1, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search KCNH3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KCNH3

genes like me logo Genes that share disorders with KCNH3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KCNH3 Gene

Publications for KCNH3 Gene

  1. New ether-à-go-go K(+) channel family members localized in human telencephalon. (PMID: 10455180) Miyake A … Furuichi K (The Journal of biological chemistry 1999) 2 3 4 23
  2. International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. (PMID: 16382104) Gutman GA … Wang X (Pharmacological reviews 2005) 2 3
  3. Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PMID: 10574462) Nagase T … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1999) 3 4
  4. Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate. (PMID: 26503718) Li X … Jegla T (The Journal of general physiology 2015) 3
  5. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. (PMID: 21873635) Gaudet P … Thomas PD (Briefings in bioinformatics 2011) 3

Products for KCNH3 Gene

Sources for KCNH3 Gene