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

Gene ID: 3757, updated on 28-Jun-2020

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
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

Genomic context

See KCNH2 in Genome Data Viewer
Location:
7q36.1
Exon count:
19
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (150944956..150978321, 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

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 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 (2020-02-26)

ClinGen Genome Curation Page
Haploinsufficency

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

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

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

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
cardiac conduction TAS
Traceable Author Statement
more info
 
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 across plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion export across plasma membrane 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 import across plasma membrane 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 IBA
Inferred from Biological aspect of Ancestor
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 
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 

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)

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
    Q12809
    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
    ENST00000461280.1
    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
    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
  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, 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

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    150944956..150978321 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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