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Genetics Home Reference: your guide to understanding genetic conditions
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KCNH2

Reviewed January 2007

What is the official name of the KCNH2 gene?

The official name of this gene is “potassium voltage-gated channel, subfamily H (eag-related), member 2.”

KCNH2 is the gene's official symbol. The KCNH2 gene is also known by other names, listed below.

What is the normal function of the KCNH2 gene?

The KCNH2 gene belongs to a large family of genes that provide instructions for making potassium channels. These channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

The specific function of a potassium channel depends on its protein components and its location in the body. Channels made with the KCNH2 protein are active in heart (cardiac) muscle, where they transport potassium ions out of cells. This form of ion transport is involved in recharging the cardiac muscle after each heartbeat to maintain a regular rhythm. The KCNH2 protein is also produced in nerve cells and certain immune cells (microglia) in the central nervous system.

The proteins produced from the KCNH2 gene and another gene, KCNE2, interact to form a functional potassium channel. Four alpha subunits, each produced from the KCNH2 gene, form the structure of each channel. One beta subunit, produced from the KCNE2 gene, binds to the channel and regulates its activity.

Does the KCNH2 gene share characteristics with other genes?

The KCNH2 gene belongs to a family of genes called KCN (potassium channels).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the KCNH2 gene related to health conditions?

Romano-Ward syndrome - caused by mutations in the KCNH2 gene

Mutations in the KCNH2 gene are a common cause of Romano-Ward syndrome. More than 140 disorder-causing mutations have been identified. Some of these mutations change a single protein building block (amino acid) in the KCNH2 protein, while other mutations delete several amino acids from the protein. These changes prevent the protein from assembling into functional ion channels or alter the channels' structure and function. As a result, the channels cannot properly regulate the flow of potassium ions in cardiac muscle cells. A disruption in ion transport leads to an irregular heartbeat (arrhythmia) that increases the risk of fainting (syncope) and sudden death.

short QT syndrome - caused by mutations in the KCNH2 gene

Mutations in the KCNH2 gene are also associated with a heart condition called short QT syndrome. In a small number of families with this condition, researchers have identified a mutation that replaces the amino acid asparagine with the amino acid lysine at position 588 of the KCNH2 protein (written as Asn588Lys or N588K). This switch in amino acids disrupts the usual function of ion channels made with the KCNH2 protein, increasing the channels' activity. By allowing more potassium ions to flow out of cardiac muscle cells at a critical time during the heartbeat, the N588K mutation is likely responsible for the changes in heart rhythm found in short QT syndrome.

other disorders - associated with the KCNH2 gene

Certain drugs, including medications used to treat arrhythmias, infections, seizures, and psychotic disorders, can lead to an abnormal heart rhythm in some people. This drug-induced heart condition, which is known as acquired long QT syndrome, increases the risk of cardiac arrest and sudden death. A small percentage of cases of acquired long QT syndrome occur in people who have an underlying mutation in the KCNH2 gene.

Where is the KCNH2 gene located?

Cytogenetic Location: 7q36.1

Molecular Location on chromosome 7: base pairs 150,642,043 to 150,675,401

The KCNH2 gene is located on the long (q) arm of chromosome 7 at position 36.1.

The KCNH2 gene is located on the long (q) arm of chromosome 7 at position 36.1.

More precisely, the KCNH2 gene is located from base pair 150,642,043 to base pair 150,675,401 on chromosome 7.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about KCNH2?

You and your healthcare professional may find the following resources about KCNH2 helpful.

  • Educational resources - Information pages
    Neuromuscular Disease Center, Washington University: KCNH family of potassium channels (http://neuromuscular.wustl.edu/mother/chan.html)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=rws)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for KCNH2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=3757%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(KCNH2%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/152427)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_KCNH2.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/3757)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=3757)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=6251)
    • International Registry for Drug-Induced Arrhythmias (http://www.azcert.org/medical-pros/qt-registry/)

What other names do people use for the KCNH2 gene or gene products?

  • Eag related protein 1
  • ERG1
  • Ether-a-go-go related gene potassium channel 1
  • HERG
  • HERG1
  • human ether a-go-go-related gene
  • KCNH2_HUMAN
  • Kv11.1
  • LQT2

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding KCNH2?

acids ; amino acid ; arrhythmia ; cardiac ; cardiac arrest ; cell ; central nervous system ; channel ; fainting ; gene ; ions ; ion transport ; long QT syndrome ; microglia ; mutation ; nervous system ; potassium ; protein ; psychotic ; subunit ; syncope ; syndrome ; voltage

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, Menendez TM, Brugada J, Pollevick GD, Wolpert C, Burashnikov E, Matsuo K, Wu YS, Guerchicoff A, Bianchi F, Giustetto C, Schimpf R, Brugada P, Antzelevitch C. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation. 2004 Jan 6;109(1):30-5. Epub 2003 Dec 15. (http://www.ncbi.nlm.nih.gov/pubmed/14676148?dopt=Abstract)
  • Chiang CE. Congenital and acquired long QT syndrome. Current concepts and management. Cardiol Rev. 2004 Jul-Aug;12(4):222-34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15191637?dopt=Abstract)
  • Cordeiro JM, Brugada R, Wu YS, Hong K, Dumaine R. Modulation of I(Kr) inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome. Cardiovasc Res. 2005 Aug 15;67(3):498-509. Epub 2005 Mar 28. (http://www.ncbi.nlm.nih.gov/pubmed/16039272?dopt=Abstract)
  • Emery, Alan E H; Rimoin, David L; Emery & Rimoin's principles and practice of medical genetics.; 4th ed. / edited by David L. Rimoin ... [et al.]; London ; New York : Churchill Livingstone, 2002. p1422-1423.
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/3757)
  • Gene Review: Romano-Ward Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=rws)
  • Hong K, Bjerregaard P, Gussak I, Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J Cardiovasc Electrophysiol. 2005 Apr;16(4):394-6. (http://www.ncbi.nlm.nih.gov/pubmed/15828882?dopt=Abstract)
  • Paulussen AD, Gilissen RA, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJ, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, Aerssens J. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 Mar;82(3):182-8. Epub 2004 Feb 4. (http://www.ncbi.nlm.nih.gov/pubmed/14760488?dopt=Abstract)
  • Paulussen AD, Raes A, Jongbloed RJ, Gilissen RA, Wilde AA, Snyders DJ, Smeets HJ, Aerssens J. HERG mutation predicts short QT based on channel kinetics but causes long QT by heterotetrameric trafficking deficiency. Cardiovasc Res. 2005 Aug 15;67(3):467-75. (http://www.ncbi.nlm.nih.gov/pubmed/15958262?dopt=Abstract)
  • Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M. Short QT syndrome. Cardiovasc Res. 2005 Aug 15;67(3):357-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15890322?dopt=Abstract)
  • Thomas D, Kiehn J, Katus HA, Karle CA. Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing. Cardiovasc Res. 2003 Nov 1;60(2):235-41. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14613852?dopt=Abstract)
  • Towbin JA, Vatta M. Molecular biology and the prolonged QT syndromes. Am J Med. 2001 Apr 1;110(5):385-98. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11286954?dopt=Abstract)
  • Tristani-Firouzi M, Sanguinetti MC. Structural determinants and biophysical properties of HERG and KCNQ1 channel gating. J Mol Cell Cardiol. 2003 Jan;35(1):27-35. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12623297?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2007
Published: May 13, 2013