HERG
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| potassium voltage-gated channel, subfamily H (eag-related), member 2
| |
| Identifiers | |
| Symbol | KCNH2 |
| Alt. Symbols | LQT2, Kv11.1 |
| Entrez | 3757 |
| HUGO | 6251 |
| OMIM | 152427 |
| RefSeq | NM_000238 |
| UniProt | Q12809 |
| Other data | |
| Locus | Chr. 7 q35-q36 |
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Overview
hERG (Human Ether-a-go-go Related Gene).
The hERG gene (KCNH2) encodes a potassium ion channel responsible for the repolarizing IKr current in the cardiac action potential. It has 6 transmembrane domains, numbered S1-S6.
Abnormalities in this channel may lead to either Long QT syndrome (LQT2) (with loss of function mutations) or Short QT syndrome (with gain of function mutations), both potentially fatal cardiac arrhythmia, due to repolarisation disturbances of the cardiac action potential.[1][1]
This channel is also sensitive to drug binding, as well as decreased extracellular potassium levels; both of which can result in decreased channel function, and the so-called acquired long QT syndrome. Among the drugs that can cause QT prolongation, the more common ones include antiarrhythmics (especially Class 1A and Class III), anti-psychotic agents, and certain antibiotics (including quinolones and macrolides).[1]
Although there exist other potential targets for cardiac adverse effects, the vast majority of drugs associated with acquired QT prolongation is known to interact with the hERG potassium channel. One of the main reasons for this phenomenon is the larger inner vestibule of the hERG channel, thus providing more space for many different drug classes to bind and block this potassium channel.[1]
Due to the awareness of the potential danger of such QT drugs the regulatory authorities issued recommendations for the establishment of cardiac safety during preclinical drug development: ICH S7B, The nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals, issued as CHMP/ICH/423/02, adopted by CHMP in May 2005. Preclinical hERG studies should be accomplished in GLP environment.
The name
The hERG gene is the human homolog of the Ether-a-go-go gene found in the Drosophila fly. When flies with mutations in this gene are anesthetized with ether, their legs start to shake, like the dancing then popular at the Whisky A Go-Go nightclub in West Hollywood, California. Ether-a-go-go was named in the 1960s by William D. Kaplan, now at the City of Hope Hospital in Duarte, California.
References
See also
External links
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
