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    KCNH5 potassium voltage-gated channel subfamily H member 5 [ Homo sapiens (human) ]

    Gene ID: 27133, updated on 10-Dec-2024

    Summary

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    Official Symbol
    KCNH5provided by HGNC
    Official Full Name
    potassium voltage-gated channel subfamily H member 5provided by HGNC
    Primary source
    HGNC:HGNC:6254
    See related
    Ensembl:ENSG00000140015 MIM:605716; AllianceGenome:HGNC:6254
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EAG2; hEAG2; DEE112; H-EAG2; Kv10.2
    Summary
    This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
    Expression
    Biased expression in brain (RPKM 1.4), adrenal (RPKM 0.6) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNH5 in Genome Data Viewer
    Location:
    14q23.2
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (62699464..63045458, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (56906444..57253090, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (63166182..63512176, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370529 Neighboring gene uncharacterized LOC105370528 Neighboring gene NANOG hESC enhancer GRCh37_chr14:63033845-63034401 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:63102949-63103450 Neighboring gene ATP synthase F1 subunit alpha pseudogene 4 Neighboring gene Sharpr-MPRA regulatory region 7830 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_34896 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:63248008-63248579 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_34948 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:63511437-63511940 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:63511941-63512444 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:63527728-63528286 Neighboring gene LINE-1 retrotransposable element ORF1 protein-like Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr14:63632890-63633551 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:63640011-63640186 Neighboring gene uncharacterized LOC105370530 Neighboring gene poly(ADP-ribose) polymerase 1 pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel. Zhang M, et al. Nat Commun, 2023 Mar 16. PMID 36928654, Free PMC Article
    2. Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5. Happ HC, et al. Neurology, 2023 Feb 7. PMID 36307226, Free PMC Article
    3. A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism. Galán-Vidal J, et al. Orphanet J Rare Dis, 2022 Sep 6. PMID 36068614, Free PMC Article
    4. Molecular identification and characterisation of the human eag2 potassium channel. Ju M, et al. FEBS Lett, 2002 Jul 31. PMID 12135768
    5. [Three-dimensional structure of human Kv10.2 ion channel studied by single particle electron microscopy and molecular modeling]. Sokolova OS, et al. Bioorg Khim, 2012 Mar-Apr. PMID 22792721

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel.
      Title: Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel.
    2. Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.
      Title: Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.
    3. A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism.
      Title: A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism.
    4. Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population.
      Title: Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population.
    5. Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth.
      Title: Chloride intracellular channel 1 cooperates with potassium channel EAG2 to promote medulloblastoma growth.
    6. EAG2 potassium channel has an evolutionarily conserved function for promoting brain tumor growth.
      Title: EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.
    7. The observed Ca(2+)-induced proteolytic cleavage of EAG2 channel may act as an adaptive response under physiological and/or pathological conditions.
      Title: A sustained increase in the intracellular Ca²⁺ concentration induces proteolytic cleavage of EAG2 channel.
    8. Study propose that hypomethylation of the placental-specific KCNH5 promoter is frequently associated with KCNH5 expression in melanoma cells.
      Title: Retrotransposon hypomethylation in melanoma and expression of a placenta-specific gene.
    9. Our results demonstrate the critical role of the Arg327 residue in stabilizing the channel closed state and explicate for the first time the structural and functional change of a Kv10.2 channel mutation associated with neurological disease.
      Title: Multistate structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state.
    10. This study performed whole exome sequencing demonistrated that the true de novo variants represent mutations in genes (KCNH5, CLCN4, and ARHGEF15) not previously associated with epilepsies in humans.
      Title: Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Developmental and epileptic encephalopathy 112
    MedGen: C5882700 OMIM: 620537 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
    EBI GWAS Catalog
    EMR-linked GWAS study: investigation of variation landscape of loci for body mass index in children.
    EBI GWAS Catalog
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    EBI GWAS Catalog
    The Contribution of Common Genetic Variation to Nicotine and Cotinine Glucuronidation in Multiple Ethnic/Racial Populations.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables delayed rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transmembrane transporter binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables voltage-gated potassium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables voltage-gated potassium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in potassium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in potassium ion transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of G2/M transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of membrane potential IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of voltage-gated potassium channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of voltage-gated potassium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    voltage-gated delayed rectifier potassium channel KCNH5; potassium voltage-gated channel subfamily H member 5
    Names
    ether-a-go-go 2
    ether-a-go-go-related potassium channel 2
    potassium channel, voltage gated eag related subfamily H, member 5
    potassium voltage-gated channel, subfamily H (eag-related), member 5
    voltage-gated potassium channel subunit Kv10.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_034062.2 RefSeqGene

      Range
      5000..350994
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_139318.5 → NP_647479.2  voltage-gated delayed rectifier potassium channel KCNH5 isoform 1

      See identical proteins and their annotated locations for NP_647479.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AF472412, AL132666, AL355101, BC073979
      Consensus CDS
      CCDS9756.1
      UniProtKB/Swiss-Prot
      C9JP98, Q8NCM2
      Related
      ENSP00000321427.7, ENST00000322893.12
      Conserved Domains (3) summary
      PLN03192
      Location:217 → 616
      PLN03192; Voltage-dependent potassium channel; Provisional
      COG0664
      Location:544 → 725
      Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
      pfam13426
      Location:39 → 132
      PAS_9; PAS domain

    2. NM_172375.3 → NP_758963.1  voltage-gated delayed rectifier potassium channel KCNH5 isoform 3

      See identical proteins and their annotated locations for NP_758963.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as HEAG2b, lacks an exon in the coding region, which results in a frameshift and an early stop codon, as compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, as compared to isoform 1.
      Source sequence(s)
      AF493798, AL132666, AL355101
      Consensus CDS
      CCDS45122.1
      UniProtKB/Swiss-Prot
      Q8NCM2
      Related
      ENSP00000395439.2, ENST00000420622.6
      Conserved Domains (2) summary
      PLN03192
      Location:217 → 607
      PLN03192; Voltage-dependent potassium channel; Provisional
      pfam13426
      Location:39 → 132
      PAS_9; PAS domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      62699464..63045458 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431275.1 → XP_047287231.1  potassium voltage-gated channel subfamily H member 5 isoform X1

      Related
      ENSP00000378419.1, ENST00000394968.2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      56906444..57253090 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375872.1 → XP_054231847.1  potassium voltage-gated channel subfamily H member 5 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_172376.1: Suppressed sequence

      Description
      NM_172376.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NCM2.3 GenPept UniProtKB/Swiss-Prot:Q8NCM2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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