U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

    KCNH2 potassium voltage-gated channel subfamily H member 2 [ Homo sapiens (human) ]

    Gene ID: 3757, updated on 17-Jun-2024

    Summary

    Official Symbol
    KCNH2provided by HGNC
    Official Full Name
    potassium voltage-gated channel subfamily H member 2provided by HGNC
    Primary source
    HGNC:HGNC:6251
    See related
    Ensembl:ENSG00000055118 MIM:152427; AllianceGenome:HGNC:6251
    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
    ERG1; HERG; LQT2; SQT1; ERG-1; H-ERG; HERG1; Kv11.1
    Summary
    This gene encodes a component of a voltage-activated potassium channel found in cardiac muscle, nerve cells, and microglia. Four copies of this protein interact with one copy of the KCNE2 protein to form a functional potassium channel. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, May 2022]
    Expression
    Broad expression in bone marrow (RPKM 13.5), testis (RPKM 10.7) and 14 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See KCNH2 in Genome Data Viewer
    Location:
    7q36.1
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (150944961..150978321, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (152117824..152151201, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (150642049..150675409, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375567 Neighboring gene uncharacterized LOC124901775 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150549187-150549758 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150553923-150554766 Neighboring gene amine oxidase copper containing 1 Neighboring gene Sharpr-MPRA regulatory region 11983 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150607062-150607562 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150642260-150643002 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150643003-150643744 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150645973-150646713 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150651428-150652026 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150654831-150655332 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150658991-150659600 Neighboring gene VISTA enhancer hs2192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150669129-150669642 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18785 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18786 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18787 Neighboring gene uncharacterized LOC124901776 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150672781-150673707 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18788 Neighboring gene NOS3 5' regulatory region Neighboring gene ReSE screen-validated silencer GRCh37_chr7:150697314-150697476 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:150698330-150699529 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150703744-150704324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150704325-150704905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26844 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150710378-150711069 Neighboring gene nitric oxide synthase 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18790 Neighboring gene uncharacterized LOC124901777 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150722492-150723096 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:150723702-150724305 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:150724306-150724910 Neighboring gene autophagy related 9B

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in KCNH2 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    Long QT syndrome
    MedGen: C0023976 GeneReviews: Long QT Syndrome Overview
    Compare labs
    Long QT syndrome 2
    MedGen: C3150943 OMIM: 613688 GeneReviews: Long QT Syndrome Overview
    Compare labs
    Short QT syndrome type 1
    MedGen: C1865020 OMIM: 609620 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-02-26)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-02-26)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Common variants at ten loci influence QT interval duration in the QTGEN Study.
    EBI GWAS Catalog
    Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
    EBI GWAS Catalog
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
    EBI GWAS Catalog
    Genetic variation in SCN10A influences cardiac conduction.
    EBI GWAS Catalog
    Impact of ancestry and common genetic variants on QT interval in African Americans.
    EBI GWAS Catalog
    Several common variants modulate heart rate, PR interval and QRS duration.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat protein inhibits hERG K(+) currents through the inhibition of hERG protein expression PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables C3HC4-type RING finger domain binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables delayed rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables delayed rectifier potassium channel activity IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables inward rectifier potassium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables inward rectifier potassium channel activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables inward rectifier potassium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables scaffold protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables transcription cis-regulatory region binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables voltage-gated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization IC
    Inferred by Curator
    more info
    PubMed 
    enables voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to xenobiotic stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in membrane depolarization during action potential IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in membrane repolarization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in membrane repolarization during action potential IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in membrane repolarization during cardiac muscle cell action potential IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in membrane repolarization during cardiac muscle cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in membrane repolarization during ventricular cardiac muscle cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of potassium ion export across plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in potassium ion export across plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in potassium ion export across plasma membrane IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in potassium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in potassium ion import across plasma membrane IDA
    Inferred from Direct Assay
    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 regulation of heart rate by cardiac conduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    acts_upstream_of_or_within regulation of heart rate by cardiac conduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of heart rate by cardiac conduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of heart rate by hormone TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of membrane potential IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of membrane repolarization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of ventricular cardiac muscle cell membrane repolarization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of ventricular cardiac muscle cell membrane repolarization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in ventricular cardiac muscle cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of inward rectifier potassium channel complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    located_in perinuclear region of cytoplasm IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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
     
    part_of voltage-gated potassium channel complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of voltage-gated potassium channel complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 

    General protein information

    Preferred Names
    potassium voltage-gated channel subfamily H member 2
    Names
    eag homolog
    eag-related protein 1
    ether-a-go-go-related gene potassium channel 1
    ether-a-go-go-related potassium channel protein
    ether-a-go-go-related protein 1
    human ether-a-go-go-related
    long QT syndrome type 2
    potassium channel, voltage gated eag related subfamily H, member 2
    potassium voltage-gated channel, subfamily H (eag-related), member 2
    voltage-gated potassium channel subunit Kv11.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_008916.1 RefSeqGene

      Range
      4613..37971
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_288

    mRNA and Protein(s)

    1. NM_000238.4NP_000229.1  potassium voltage-gated channel subfamily H member 2 isoform a

      See identical proteins and their annotated locations for NP_000229.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AC011234, AF363636, DQ525913, U04270
      Consensus CDS
      CCDS5910.1
      UniProtKB/Swiss-Prot
      A5H1P7, C4PFH9, D3DX04, O75418, O75680, Q12809, Q708S9, Q9BT72, Q9BUT7, Q9H3P0
      UniProtKB/TrEMBL
      A0A090N8Q0, Q15BH2
      Related
      ENSP00000262186.5, ENST00000262186.10
      Conserved Domains (4) summary
      cd00038
      Location:742853
      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 ...
      pfam00520
      Location:409668
      Ion_trans; Ion transport protein
      pfam13426
      Location:29130
      PAS_9; PAS domain
      pfam15836
      Location:10121113
      SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein
    2. NM_001204798.2NP_001191727.1  potassium voltage-gated channel subfamily H member 2 isoform d

      See identical proteins and their annotated locations for NP_001191727.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' and 3' UTRs and 5' and 3' coding regions compared to variant 1, resulting in a shorter isoform (d) with different N- and C-termini compared to isoform a.
      Source sequence(s)
      AJ609614, BC001914, BG683210, BQ478289
      UniProtKB/Swiss-Prot
      Q12809
      Related
      ENST00000461280.2
      Conserved Domains (3) summary
      smart00100
      Location:402462
      cNMP; Cyclic nucleotide-monophosphate binding domain
      pfam00520
      Location:109328
      Ion_trans; Ion transport protein
      pfam07885
      Location:271325
      Ion_trans_2; Ion channel
    3. NM_001406753.1NP_001393682.1  potassium voltage-gated channel subfamily H member 2 isoform e

      Status: REVIEWED

      Source sequence(s)
      AC006343
      UniProtKB/TrEMBL
      Q15BH2
      Related
      ENST00000684241.1
    4. NM_001406755.1NP_001393684.1  potassium voltage-gated channel subfamily H member 2 isoform f

      Status: REVIEWED

      Source sequence(s)
      AC006343, AC011234
      UniProtKB/TrEMBL
      Q86U57
      Related
      ENST00000713700.1
    5. NM_001406756.1NP_001393685.1  potassium voltage-gated channel subfamily H member 2 isoform g

      Status: REVIEWED

      Source sequence(s)
      AC006343
      UniProtKB/TrEMBL
      Q86U57
    6. NM_001406757.1NP_001393686.1  potassium voltage-gated channel subfamily H member 2 isoform h

      Status: REVIEWED

      Source sequence(s)
      AC006343, AC011234
      UniProtKB/TrEMBL
      Q86U57
    7. NM_172056.3NP_742053.1  potassium voltage-gated channel subfamily H member 2 isoform b

      See identical proteins and their annotated locations for NP_742053.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as HERG-USO, differs in the 3' UTR and 3' coding region compared to variant 1, resulting in a shorter isoform (b) with a different C-terminus compared to isoform a.
      Source sequence(s)
      AC006343, AC011234
      UniProtKB/TrEMBL
      A0A090N7W1, Q86U57
      Related
      ENST00000532957.5
      Conserved Domains (5) summary
      smart00100
      Location:742802
      cNMP; Cyclic nucleotide-monophosphate binding domain
      cd00130
      Location:41132
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00520
      Location:449668
      Ion_trans; Ion transport protein
      pfam07885
      Location:611665
      Ion_trans_2; Ion channel
      pfam13426
      Location:29130
      PAS_9; PAS domain
    8. NM_172057.3NP_742054.1  potassium voltage-gated channel subfamily H member 2 isoform c

      See identical proteins and their annotated locations for NP_742054.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as HERG1b, differs in the 5' UTR and 5' coding region compared to variant 1, resulting in a shorter isoform (c) with a different N-terminus compared to isoform a.
      Source sequence(s)
      AC006343
      Consensus CDS
      CCDS5911.1
      UniProtKB/TrEMBL
      A0A090N7X5
      Related
      ENSP00000328531.4, ENST00000330883.9
      Conserved Domains (5) summary
      COG0664
      Location:396516
      Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
      cd00038
      Location:402513
      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 ...
      pfam00520
      Location:109328
      Ion_trans; Ion transport protein
      pfam07885
      Location:271325
      Ion_trans_2; Ion channel
      pfam15836
      Location:672773
      SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein

    RNA

    1. NR_176254.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC006343, AC011234
    2. NR_176255.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC006343

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      150944961..150978321 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420348.1XP_047276304.1  potassium voltage-gated channel subfamily H member 2 isoform X1

      UniProtKB/TrEMBL
      Q15BH2
    2. XM_017012196.2XP_016867685.1  potassium voltage-gated channel subfamily H member 2 isoform X3

      UniProtKB/TrEMBL
      Q15BH2
    3. XM_011516185.3XP_011514487.1  potassium voltage-gated channel subfamily H member 2 isoform X4

      UniProtKB/TrEMBL
      Q15BH2
      Related
      ENSP00000519004.1, ENST00000713701.1
      Conserved Domains (5) summary
      COG0664
      Location:636756
      Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
      cd00038
      Location:642753
      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 ...
      pfam00520
      Location:349568
      Ion_trans; Ion transport protein
      pfam07885
      Location:511565
      Ion_trans_2; Ion channel
      pfam15836
      Location:9121013
      SSTK-IP; SSTK-interacting protein, TSSK6-activating co-chaperone protein
    4. XM_017012195.2XP_016867684.1  potassium voltage-gated channel subfamily H member 2 isoform X2

      UniProtKB/TrEMBL
      Q15BH2
      Conserved Domains (1) summary
      PLN03192
      Location:360797
      PLN03192; Voltage-dependent potassium channel; Provisional
    5. XM_047420349.1XP_047276305.1  potassium voltage-gated channel subfamily H member 2 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      152117824..152151201 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358168.1XP_054214143.1  potassium voltage-gated channel subfamily H member 2 isoform X1

      UniProtKB/TrEMBL
      Q15BH2
    2. XM_054358170.1XP_054214145.1  potassium voltage-gated channel subfamily H member 2 isoform X3

      UniProtKB/TrEMBL
      Q15BH2
    3. XM_054358171.1XP_054214146.1  potassium voltage-gated channel subfamily H member 2 isoform X4

      UniProtKB/TrEMBL
      Q15BH2
    4. XM_054358169.1XP_054214144.1  potassium voltage-gated channel subfamily H member 2 isoform X2

      UniProtKB/TrEMBL
      Q15BH2
    5. XM_054358172.1XP_054214147.1  potassium voltage-gated channel subfamily H member 2 isoform X5