Human Gene KCNH2 (ENST00000262186.10) from GENCODE V44
  Description: Homo sapiens potassium voltage-gated channel subfamily H member 2 (KCNH2), transcript variant 1, mRNA. (from RefSeq NM_000238)
RefSeq Summary (NM_000238): 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].
Gencode Transcript: ENST00000262186.10
Gencode Gene: ENSG00000055118.17
Transcript (Including UTRs)
   Position: hg38 chr7:150,944,961-150,978,321 Size: 33,361 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg38 chr7:150,945,365-150,977,913 Size: 32,549 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr7:150,944,961-150,978,321)mRNA (may differ from genome)Protein (1159 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Potassium voltage-gated channel subfamily H member 2; AltName: Full=Eag homolog; AltName: Full=Ether-a-go-go-related gene potassium channel 1; Short=ERG-1; Short=Eag-related protein 1; Short=Ether-a-go-go-related protein 1; Short=H-ERG; Short=hERG-1; Short=hERG1; AltName: Full=Voltage-gated potassium channel subunit Kv11.1;
FUNCTION: Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1.
SUBUNIT: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3. Interacts with ALG10B (By similarity). Heteromultimer with KCNE1 and KCNE2. Interacts with CANX.
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Highly expressed in heart and brain.
DOMAIN: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
PTM: Phosphorylated on serine and threonine residues. Phosphorylation by PKA inhibits ion conduction.
DISEASE: Defects in KCNH2 are the cause of long QT syndrome type 2 (LQT2) [MIM:613688]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress. Deafness is often associated with LQT2.
DISEASE: Defects in KCNH2 are the cause of short QT syndrome type 1 (SQT1) [MIM:609620]. Short QT syndromes are heart disorders characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. They cause syncope and sudden death.
SIMILARITY: Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily.
SIMILARITY: Contains 1 cyclic nucleotide-binding domain.
SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain.
SIMILARITY: Contains 1 PAS (PER-ARNT-SIM) domain.
SEQUENCE CAUTION: Sequence=AAC69709.1; Type=Miscellaneous discrepancy; Note=Cloning artifact; Sequence=AAH01914.2; Type=Miscellaneous discrepancy; Note=Cloning artifact; Sequence=BAB19682.1; Type=Miscellaneous discrepancy; Note=Cloning artifact; Sequence=CAA09232.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=GeneReviews; URL="";
WEB RESOURCE: Name=Wikipedia; Note=Ether-a-go-go potassium channels entry; URL="";

-  Primer design for this transcript

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-  MalaCards Disease Associations
  MalaCards Gene Search: KCNH2
Diseases sorted by gene-association score: long qt syndrome 2* (1429), short qt syndrome 1* (1329), familial short qt syndrome* (768), familial long qt syndrome* (444), long qt syndrome* (339), short qt syndrome* (317), long qt syndrome 5* (301), cardiac conduction disease with or without dilated cardiomyopathy* (200), long qt syndrome 1* (169), sudden cardiac death (22), intrinsic cardiomyopathy (20), fainting (18), syncope (16), atrioventricular block (15), brugada syndrome (15), jervell and lange-nielsen syndrome (14), long qt syndrome-3 (13), sudden infant death syndrome (13), long qt syndrome 13 (11), heart disease (10), long qt syndrome 6 (10), ventricular fibrillation, familial, 1 (9), hypokalemia (9), ventricular tachycardia, catecholaminergic polymorphic, 1 (8), long qt syndrome 12 (8), catecholaminergic polymorphic ventricular tachycardia (7), timothy syndrome (6), heart conduction disease (5), familial atrial fibrillation (5), myasthenic syndrome, congenital, 5 (5), atrial fibrillation (3), tetralogy of fallot (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 34.01 RPKM in Pituitary
Total median expression: 299.33 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -289.50408-0.710 Picture PostScript Text
3' UTR -165.30404-0.409 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR018490 - cNMP-bd-like
IPR000595 - cNMP-bd_dom
IPR005821 - Ion_trans_dom
IPR003938 - K_chnl_volt-dep_EAG/ELK/ERG
IPR003967 - K_chnl_volt-dep_ERG
IPR001610 - PAC
IPR000014 - PAS
IPR000700 - PAS-assoc_C
IPR014710 - RmlC-like_jellyroll

Pfam Domains:
PF00027 - Cyclic nucleotide-binding domain
PF00520 - Ion transport protein

Protein Data Bank (PDB) 3-D Structure
MuPIT help

ModBase Predicted Comparative 3D Structure on Q12809
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000155 phosphorelay sensor kinase activity
GO:0005216 ion channel activity
GO:0005242 inward rectifier potassium channel activity
GO:0005244 voltage-gated ion channel activity
GO:0005249 voltage-gated potassium channel activity
GO:0005251 delayed rectifier potassium channel activity
GO:0005267 potassium channel activity
GO:0005515 protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0055131 C3HC4-type RING finger domain binding
GO:0086008 voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization
GO:0097110 scaffold protein binding
GO:1902282 voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization

Biological Process:
GO:0000160 phosphorelay signal transduction system
GO:0003064 regulation of heart rate by hormone
GO:0006811 ion transport
GO:0006813 potassium ion transport
GO:0023014 signal transduction by protein phosphorylation
GO:0034765 regulation of ion transmembrane transport
GO:0035690 cellular response to drug
GO:0042391 regulation of membrane potential
GO:0055075 potassium ion homeostasis
GO:0055085 transmembrane transport
GO:0060048 cardiac muscle contraction
GO:0060306 regulation of membrane repolarization
GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization
GO:0071435 potassium ion export
GO:0071805 potassium ion transmembrane transport
GO:0086005 ventricular cardiac muscle cell action potential
GO:0086009 membrane repolarization
GO:0086010 membrane depolarization during action potential
GO:0086011 membrane repolarization during action potential
GO:0086013 membrane repolarization during cardiac muscle cell action potential
GO:0086091 regulation of heart rate by cardiac conduction
GO:0097623 potassium ion export across plasma membrane
GO:0098915 membrane repolarization during ventricular cardiac muscle cell action potential
GO:1901379 regulation of potassium ion transmembrane transport
GO:1901380 negative regulation of potassium ion transmembrane transport
GO:1901381 positive regulation of potassium ion transmembrane transport
GO:1902303 negative regulation of potassium ion export

Cellular Component:
GO:0005886 plasma membrane
GO:0008076 voltage-gated potassium channel complex
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0048471 perinuclear region of cytoplasm
GO:1902937 inward rectifier potassium channel complex

-  Descriptions from all associated GenBank mRNAs
  BC004311 - Homo sapiens potassium voltage-gated channel, subfamily H (eag-related), member 2, mRNA (cDNA clone IMAGE:3627585), partial cds.
FJ938021 - Homo sapiens voltage-gated potassium channel subfamily H isoform 3.1 (KCNH2) mRNA, complete cds, alternatively spliced.
U04270 - Human putative potassium channel subunit (h-erg) mRNA, complete cds.
DQ525913 - Homo sapiens voltage-gated potassium channel KV11.1 transcript variant 1 mRNA, complete cds.
JD136914 - Sequence 117938 from Patent EP1572962.
JD278048 - Sequence 259072 from Patent EP1572962.
JD393346 - Sequence 374370 from Patent EP1572962.
JD371545 - Sequence 352569 from Patent EP1572962.
BC127672 - Homo sapiens cDNA clone IMAGE:40128611.
BC127673 - Homo sapiens potassium voltage-gated channel, subfamily H (eag-related), member 2, mRNA (cDNA clone IMAGE:40128615), complete cds.
JD340218 - Sequence 321242 from Patent EP1572962.
JD560230 - Sequence 541254 from Patent EP1572962.
JD465579 - Sequence 446603 from Patent EP1572962.
BC167862 - Synthetic construct Homo sapiens clone IMAGE:100068252, MGC:195869 potassium voltage-gated channel, subfamily H (eag-related), member 2 (KCNH2) mRNA, encodes complete protein.
AJ512214 - Homo sapiens mRNA for potassium channel 1b protein (HERG1b gene).
AF363636 - Homo sapiens ether-a-go-go-related K+ channel protein (KCNH2) mRNA, complete cds.
AF052728 - Homo sapiens HERG-USO (HERG) mRNA, alternatively spliced, partial cds.
AJ609614 - Homo sapiens mRNA for potassium voltage-gated channel, subfamily H (eag-related), member 2, putative transcript variant 4, (KCNH2 gene).
BC080563 - Homo sapiens cDNA clone IMAGE:6340663, **** WARNING: chimeric clone ****.
BC001914 - Homo sapiens potassium voltage-gated channel, subfamily H (eag-related), member 2, mRNA (cDNA clone IMAGE:3510423), partial cds.
AB044806 - Homo sapiens HERG mRNA for HERG-USO, alternatively spliced, complete cds.
AY927502 - Homo sapiens mRNA sequence.
BT007336 - Homo sapiens potassium voltage-gated channel, subfamily H (eag-related), member 2 mRNA, complete cds.
DQ120125 - Homo sapiens voltage-gated potassium channel mRNA, 5' UTR and partial cds.
DQ120124 - Homo sapiens potassium channel HERG1 (KCNH2) mRNA, 5' UTR and partial cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q12809 (Reactome details) participates in the following event(s):

R-HSA-5577237 KCNH2:KCNE transport K+ from cytosol to extracellular region
R-HSA-1296127 Activation of voltage gated Potassium channels
R-HSA-5576890 Phase 3 - rapid repolarisation
R-HSA-5576891 Cardiac conduction
R-HSA-397014 Muscle contraction
R-HSA-1296072 Voltage gated Potassium channels
R-HSA-1296071 Potassium Channels
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: A5H1P7, D3DX04, ENST00000262186.1, ENST00000262186.2, ENST00000262186.3, ENST00000262186.4, ENST00000262186.5, ENST00000262186.6, ENST00000262186.7, ENST00000262186.8, ENST00000262186.9, ERG, ERG1, HERG, KCNH2_HUMAN, NM_000238, O75418, O75680, Q12809, Q9BT72, Q9BUT7, Q9H3P0, uc003wic.1, uc003wic.2, uc003wic.3, uc003wic.4, uc003wic.5
UCSC ID: ENST00000262186.10
RefSeq Accession: NM_000238
Protein: Q12809 (aka KCNH2_HUMAN or KCH2_HUMAN)
CCDS: CCDS5910.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene KCNH2:
brugada (Brugada Syndrome)
rws (Long QT Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.