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KCNH1 potassium voltage-gated channel subfamily H member 1 [ Homo sapiens (human) ]

Gene ID: 3756, updated on 10-Dec-2024

Summary

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Official Symbol
KCNH1provided by HGNC
Official Full Name
potassium voltage-gated channel subfamily H member 1provided by HGNC
Primary source
HGNC:HGNC:6250
See related
Ensembl:ENSG00000143473 MIM:603305; AllianceGenome:HGNC:6250
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
EAG; EAG1; ZLS1; hEAG; TMBTS; h-eag; hEAG1; Kv10.1; K(V)10.1
Summary
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, subfamily H. This member is a pore-forming (alpha) subunit of a voltage-gated non-inactivating delayed rectifier potassium channel. It is activated at the onset of myoblast differentiation. The gene is highly expressed in brain and in myoblasts. Overexpression of the gene may confer a growth advantage to cancer cells and favor tumor cell proliferation. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
Expression
Biased expression in brain (RPKM 4.3), adrenal (RPKM 0.4) and 3 other tissues See more
Orthologs
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Genomic context

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See KCNH1 in Genome Data Viewer
Location:
1q32.2
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (210678314..211134148, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (209920145..210379828, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (210851656..211307490, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:210547305-210548216 Neighboring gene Sharpr-MPRA regulatory region 10816 Neighboring gene RNA, U5A small nuclear 8, pseudogene Neighboring gene hedgehog acyltransferase Neighboring gene BPNT2 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 9170 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210770524-210771385 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210771386-210772246 Neighboring gene Sharpr-MPRA regulatory region 1701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2479 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2480 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:210863521-210864021 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2481 Neighboring gene uncharacterized LOC105372901 Neighboring gene MPRA-validated peak678 silencer Neighboring gene MPRA-validated peak679 silencer Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3130 Neighboring gene MPRA-validated peak680 silencer Neighboring gene importin 8 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 3630 Neighboring gene MPRA-validated peak681 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr1:211306707-211306897 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1781 Neighboring gene KCNH1 intronic transcript 1 Neighboring gene PRELID1 pseudogene 5 Neighboring gene ribosomal protein S25 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. Alternatively Spliced Isoforms of KV10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes. Ramos Gomes F, et al. J Biol Chem, 2015 Dec 18. PMID 26518875, Free PMC Article
  2. Dynamics of the EAG1 K(+) channel selectivity filter assessed by molecular dynamics simulations. Bernsteiner H, et al. Biochem Biophys Res Commun, 2017 Feb 26. PMID 28109880, Free PMC Article
  3. Molecular Insights into the Mechanism of Calmodulin Inhibition of the EAG1 Potassium Channel. Marques-Carvalho MJ, et al. Structure, 2016 Oct 4. PMID 27618660, Free PMC Article
  4. Crystal structure of the PAS domain of the hEAG potassium channel. Tang X, et al. Acta Crystallogr F Struct Biol Commun, 2016 Aug. PMID 27487920, Free PMC Article
  5. Frequent aberrant expression of the human ether à go-go (hEAG1) potassium channel in head and neck cancer: pathobiological mechanisms and clinical implications. Menéndez ST, et al. J Mol Med (Berl), 2012 Oct. PMID 22466864

See all (114) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing.
    Title: Phenotypic and genetic analysis of children with unexplained neurodevelopmental delay and neurodevelopmental comorbidities in a Chinese cohort using trio-based whole-exome sequencing.
  2. Phenotypic expansion of KCNH1-associated disorders to include isolated epilepsy and its associations with genotypes and molecular sub-regional locations.
    Title: Phenotypic expansion of KCNH1-associated disorders to include isolated epilepsy and its associations with genotypes and molecular sub-regional locations.
  3. Potassium Channel KCNH1 Activating Variants Cause Altered Functional and Morphological Ciliogenesis.
    Title: Potassium Channel KCNH1 Activating Variants Cause Altered Functional and Morphological Ciliogenesis.
  4. Patients with KCNH1-related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome.
    Title: Patients with KCNH1-related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome.
  5. Hysteretic hERG channel gating current recorded at physiological temperature.
    Title: Hysteretic hERG channel gating current recorded at physiological temperature.
  6. Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
    Title: Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
  7. Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of KV10.1 Pore Blockers.
    Title: Molecular Dynamics-Derived Pharmacophore Model Explaining the Nonselective Aspect of K(V)10.1 Pore Blockers.
  8. Insights into the Molecular Inhibition of the Oncogenic Channel KV10.1 by Globular Toxins.
    Title: Insights into the Molecular Inhibition of the Oncogenic Channel K(V)10.1 by Globular Toxins.
  9. Novel KCNH1 Mutations Associated with Epilepsy: Broadening the Phenotypic Spectrum of KCNH1-Associated Diseases.
    Title: Novel KCNH1 Mutations Associated with Epilepsy: Broadening the Phenotypic Spectrum of KCNH1-Associated Diseases.
  10. High-throughput phenotyping of heteromeric human ether-a-go-go-related gene potassium channel variants can discriminate pathogenic from rare benign variants.
    Title: High-throughput phenotyping of heteromeric human ether-à-go-go-related gene potassium channel variants can discriminate pathogenic from rare benign variants.
Submit: New GeneRIF Correction See all GeneRIFs (86)

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
Temple-Baraitser syndrome
MedGen: C2678486 OMIM: 611816 GeneReviews: Not available
Compare labs
Zimmermann-Laband syndrome 1
MedGen: C4551773 OMIM: 135500 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2023-06-28)

ClinGen Genome Curation Page
Haploinsufficency

No evidence available (Last evaluated 2023-06-28)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.
EBI GWAS Catalog
Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1.
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

Clone Names

  • MGC142269

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calmodulin binding IEA
Inferred from Electronic Annotation
more info
  
NOT enables cyclic nucleotide binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables delayed rectifier potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables delayed rectifier potassium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphatidylinositol bisphosphate binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cellular response to calcium ion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in myoblast fusion TAS
Traceable Author Statement
more info
 PubMed 
involved_in potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in potassium ion transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in axon IEA
Inferred from Electronic Annotation
more info
  
located_in dendrite IEA
Inferred from Electronic Annotation
more info
  
located_in early endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in nuclear inner membrane IEA
Inferred from Electronic Annotation
more info
  
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in postsynaptic density membrane IEA
Inferred from Electronic Annotation
more info
  
located_in presynaptic membrane IEA
Inferred from Electronic Annotation
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 KCNH1; potassium voltage-gated channel subfamily H member 1
Names
EAG channel 1
ether-a-go-go 1
ether-a-go-go potassium channel 1
ether-a-go-go, Drosophila, homolog of
potassium channel, voltage gated eag related subfamily H, member 1
potassium voltage-gated channel, subfamily H (eag-related), member 1
voltage-gated potassium channel subunit Kv10.1

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_029777.2 RefSeqGene

    Range
    4968..460802
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002238.4 → NP_002229.1  voltage-gated delayed rectifier potassium channel KCNH1 isoform 2

    See identical proteins and their annotated locations for NP_002229.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as eag, lacks an alternate in-frame segment, as compared to variant 1. It encodes isoform 2, which is shorter but has the same N- and C-termini as isoform 1.
    Source sequence(s)
    AC092017, AC096636, AF078741, AJ001366
    Consensus CDS
    CCDS31015.1
    UniProtKB/TrEMBL
    A0A977NV57
    Related
    ENSP00000492697.1, ENST00000639952.1
    Conserved Domains (3) summary
    PLN03192
    Location:220 → 620
    PLN03192; Voltage-dependent potassium channel; Provisional
    PRK11753
    Location:581 → 685
    PRK11753; cAMP-activated global transcriptional regulator CRP
    pfam13426
    Location:41 → 135
    PAS_9; PAS domain

  2. NM_172362.3 → NP_758872.1  voltage-gated delayed rectifier potassium channel KCNH1 isoform 1

    See identical proteins and their annotated locations for NP_758872.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), also known as eagB, encodes the longer isoform (1).
    Source sequence(s)
    AC092017, AC096636, AF078742, AJ001366
    Consensus CDS
    CCDS1496.1
    UniProtKB/Swiss-Prot
    B1AQ26, O76035, O95259, Q14CL3
    UniProtKB/TrEMBL
    A0A977NV57
    Related
    ENSP00000271751.4, ENST00000271751.10
    Conserved Domains (3) summary
    PLN03192
    Location:220 → 647
    PLN03192; Voltage-dependent potassium channel; Provisional
    PRK11753
    Location:608 → 712
    PRK11753; cAMP-activated global transcriptional regulator CRP
    pfam13426
    Location:41 → 135
    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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    210678314..211134148 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419823.1 → XP_047275779.1  potassium voltage-gated channel subfamily H member 1 isoform X1

    UniProtKB/TrEMBL
    A0A1X7SBS6
    Related
    ENSP00000355974.5, ENST00000367007.5

  2. XM_047419829.1 → XP_047275785.1  potassium voltage-gated channel subfamily H member 1 isoform X3

    UniProtKB/TrEMBL
    A0A1W2PPA2

  3. XM_017001246.2 → XP_016856735.1  potassium voltage-gated channel subfamily H member 1 isoform X2

    UniProtKB/TrEMBL
    A0A1W2PPA2
    Conserved Domains (3) summary
    COG0664
    Location:183 → 328
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:189 → 299
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam07885
    Location:58 → 112
    Ion_trans_2; Ion channel

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    209920145..210379828 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336469.1 → XP_054192444.1  potassium voltage-gated channel subfamily H member 1 isoform X1

    UniProtKB/TrEMBL
    A0A1X7SBS6

  2. XM_054336471.1 → XP_054192446.1  potassium voltage-gated channel subfamily H member 1 isoform X3

    UniProtKB/TrEMBL
    A0A1W2PPA2

  3. XM_054336470.1 → XP_054192445.1  potassium voltage-gated channel subfamily H member 1 isoform X2

    UniProtKB/TrEMBL
    A0A1W2PPA2
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95259.1 GenPept UniProtKB/Swiss-Prot:O95259

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