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

Gene ID: 3757, updated on 3-Jun-2018
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; Vega:OTTHUMG00000158341
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 voltage-activated potassium channel belonging to the eag family. It shares sequence similarity with the Drosophila ether-a-go-go (eag) gene. Mutations in this gene can cause long QT syndrome type 2 (LQT2). Transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression
Broad expression in bone marrow (RPKM 13.5), testis (RPKM 10.7) and 14 other tissues See more
Orthologs
See KCNH2 in Genome Data Viewer
Location:
7q36.1
Exon count:
19
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 7 NC_000007.14 (150944956..150978314, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (150642044..150675402, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene transmembrane protein 176B Neighboring gene transmembrane protein 176A Neighboring gene uncharacterized LOC105375567 Neighboring gene amine oxidase, copper containing 1 Neighboring gene VISTA enhancer hs2192 Neighboring gene NOS3 5' regulatory region Neighboring gene nitric oxide synthase 3 Neighboring gene autophagy related 9B

  • 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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 2
MedGen: C3150943 OMIM: 613688 GeneReviews: Long QT Syndrome
Compare labs
Short QT syndrome 1
MedGen: C1865020 OMIM: 609620 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2016-01-14)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2016-01-14)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

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

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

  • Cardiac conduction, organism-specific biosystem (from REACTOME)
    Cardiac conduction, organism-specific biosystemThe normal sequence of contraction of atria and ventricles of the heart require activation of groups of cardiac cells. The mechanism must elicit rapid changes in heart rate and respond to changes in ...
  • Hematopoietic Stem Cell Differentiation, organism-specific biosystem (from WikiPathways)
    Hematopoietic Stem Cell Differentiation, organism-specific biosystemGrowth factors and miRNA regulating differentiation of hematopoietic stem cells (HSC) to various blood-related cell types. Note that myeloblasts branch off separately from erythrocytes and megakaryoc...
  • Muscle contraction, organism-specific biosystem (from REACTOME)
    Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
  • Neuronal System, organism-specific biosystem (from REACTOME)
    Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
  • Phase 3 - rapid repolarisation, organism-specific biosystem (from REACTOME)
    Phase 3 - rapid repolarisation, organism-specific biosystemIn phase 3 (the "rapid repolarisation" phase), the L-type Ca2+ channels close, while the slow delayed rectifier (IKs) K+ channels remain open as more K+ leak channels open. This ensures a net outward...
  • Potassium Channels, organism-specific biosystem (from REACTOME)
    Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
  • Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
    Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
  • Voltage gated Potassium channels, organism-specific biosystem (from REACTOME)
    Voltage gated Potassium channels, organism-specific biosystemVoltage-gated K+ channels (Kv) determine the excitability of heart, brain and skeletal muscle cells. Kv form octameric channel with alpha subunits that forms the pore of the channel and associated be...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
C3HC4-type RING finger domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
delayed rectifier potassium channel activity IDA
Inferred from Direct Assay
more info
PubMed 
delayed rectifier potassium channel activity IGI
Inferred from Genetic Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
inward rectifier potassium channel activity IDA
Inferred from Direct Assay
more info
PubMed 
inward rectifier potassium channel activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
phosphorelay sensor kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
scaffold protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
voltage-gated potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
voltage-gated potassium channel activity IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization IC
Inferred by Curator
more info
PubMed 
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
cardiac muscle contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to drug IDA
Inferred from Direct Assay
more info
PubMed 
membrane depolarization during action potential IDA
Inferred from Direct Assay
more info
PubMed 
membrane repolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane repolarization during action potential IDA
Inferred from Direct Assay
more info
PubMed 
membrane repolarization during cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane repolarization during ventricular cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of potassium ion export IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
phosphorelay signal transduction system IEA
Inferred from Electronic Annotation
more info
 
positive regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion export IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion export across plasma membrane IGI
Inferred from Genetic Interaction
more info
PubMed 
potassium ion homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of heart rate by cardiac conduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate by hormone TAS
Traceable Author Statement
more info
PubMed 
regulation of membrane potential IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of membrane potential IDA
Inferred from Direct Assay
more info
PubMed 
regulation of membrane repolarization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
regulation of ventricular cardiac muscle cell membrane repolarization IMP
Inferred from Mutant Phenotype
more info
PubMed 
signal transduction by protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
ventricular cardiac muscle cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inward rectifier potassium channel complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
perinuclear region of cytoplasm IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
voltage-gated potassium channel complex IDA
Inferred from Direct Assay
more info
PubMed 
voltage-gated potassium channel complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
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
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

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_000238.3NP_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)
    AF363636, BM674996, DQ525913, U04270
    Consensus CDS
    CCDS5910.1
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N8Q0, Q15BH2
    Related
    ENSP00000262186.5, OTTHUMP00000212821, ENST00000262186.9, OTTHUMT00000350741
    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_001204798.1NP_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
    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_172056.2NP_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)
    AB044806, BC001914, BQ478289, DQ525913
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N7W1, Q15BH2
    Related
    ENSP00000387657.4, ENST00000430723.4
    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
  4. NM_172057.2NP_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)
    AJ512214, BG683210, BM674996, U04270
    Consensus CDS
    CCDS5911.1
    UniProtKB/Swiss-Prot
    Q12809
    UniProtKB/TrEMBL
    A0A090N7X5
    Related
    ENSP00000328531.4, OTTHUMP00000212824, ENST00000330883.8, OTTHUMT00000350744
    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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p12 Primary Assembly

    Range
    150944956..150978314 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017012196.1XP_016867685.1  potassium voltage-gated channel subfamily H member 2 isoform X3

  2. XM_011516185.2XP_011514487.1  potassium voltage-gated channel subfamily H member 2 isoform X2

    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
  3. XM_017012195.1XP_016867684.1  potassium voltage-gated channel subfamily H member 2 isoform X1

  4. XM_011516186.3XP_011514488.1  potassium voltage-gated channel subfamily H member 2 isoform X4

    Conserved Domains (6) summary
    COG0664
    Location:736856
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    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 ...
    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
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