HERG

hERG (the human " Ether-à-go-go"-Related Gene)，人延迟整流钾离子通道基因，是指基因。该基因编码的蛋白质被称为 Kv11.1，是钾离子通道(potassium ion channel)的α亚基（alpha subunit）。该基因编码的钾离子通道（有时简单地使用'hERG'表示）最为著名的是其对心脏的电位活性，可协调心跳（即，hERG通道介导在心脏动作电位中延迟整流钾电流--"I"Kr的复极化）。当这个通道介导电流通过细胞膜的能力受到抑制或妥协让步时，不论是由于药物的作用还是某些家族的基因突变引发，，都会导致潜在的致命疾病——QT间期延长综合症。若干临床上成功的上市药物有抑制hERG的趋势，导致其在使用过程中也伴随着猝死的药物不良反应风险。因此，在药物研发过程中要尽量避免药物对抗靶标(antitarget)的hERG抑制。 hERG还跟神经系统的某些细胞功能的调节 以及白血病细胞癌症特性的建立和维持有关。
命名.
1994年4月，威斯康星大学麦迪逊分校的杰夫（Jeff Warmke)和巴里（Barry Ganetzky）在论文中首次命名和描述了hERG基因。 
hERG基因是首次发现于果蝇的"Ether-à-go-go"基因的人类同源类似物。 "Ether-à-go-go"基因由现在任职于希望城国家医学中心（City of Hope National Medical Center）的威廉·d·卡普兰在1960年代命名。当使用乙醚麻醉拥有 "Ether-à-go-go"基因突变的苍蝇时，它们的腿就开始颤抖，就像当时流行于加利福尼亚西好莱坞的威士忌摇摆舞（Whisky A Go-Go）夜总会的舞蹈。
Interactions.
HERG和 YWHAE之间存在相互作用。
生物功能.
Kr)) that conducts potassium (K+) ions out of the muscle cells of the heart (cardiac myocytes), and this current is critical in correctly timing the return to the resting state (repolarization) of the cell membrane during the cardiac action potential. Sometimes, when referring to the pharmacological effects of drugs, the terms "hERG channels" and "I"Kr are used interchangeably, but, in the technical sense, "hERG channels" can be made only by scientists in the laboratory; in formal terms, the naturally occurring channels in the body that include hERG are referred to by the name of the electrical current that has been measured in that cell type, so, for example, in the heart, the correct name is "I"Kr. This difference in nomenclature becomes clearer in the controversy as to whether the channels conducting "I"Kr include other subunits (e.g., beta subunits) or whether the channels include a mixture of different types (isoforms) of hERG, but, when the originally-discovered form of hERG is experimentally transferred into cells that previously lacked hERG (i.e., heterologous expression), a potassium ion channel is formed, and this channel has many signature features of the cardiac 'rapid' delayed rectifier current ("I"Kr), including "I"Kr's inward rectification that results in the channel producing a 'paradoxical resurgent current' in response to repolarization of the membrane.
Structure.
A detailed atomic structure for hERG based on X-ray cystallography is not yet available, so structural details for hERG are based on analogy with other ion channels, computer models, pharmacology, and mutagenesis studies. In the laboratory the heterologously expressed hERG potassium channel comprises 4 identical alpha subunits, which form the channel's pore through the plasma membrane. Each hERG subunit consists of 6 transmembrane alpha helices, numbered S1-S6, a pore helix situated between S5 and S6, and cytoplasmically located N- and C-termini. The S4 helix contains a positively charged arginine or lysine amino acid residue at every 3rd position and is thought to act as a voltage-sensitive sensor, which allows the channel to respond to voltage changes by changing conformations between conducting and non-conducting states (called 'gating'). Between the S5 and S6 helices, there is an extracellular loop (known as 'the turret') and 'the pore loop', which begins and ends extracellularly but loops into the plasma membrane; the pore loop for each of the hERG subunits in one channel face into the ion-conducting pore and are adjacent to the corresponding loops of the 3 other subunits, and together they form the selectivity filter region of the channel pore. The selectivity sequence, SVGFG, is very similar to that contained in bacterial KcsA channels. Although a full crystal structure for hERG is not yet available, a structure has been found for the cytoplasmic N-terminus, which was shown to contain a PAS domain (aminoacid 26-135) that slows the rate of deactivation.
Genetics.
Loss of function mutations in this channel may lead to long QT syndrome (LQT2), while gain of function mutations may lead to short QT syndrome. Both clinical disorders stem from ion channel dysfunction (so-called channelopathies) that can lead to the risk of potentially fatal cardiac arrhythmias (e.g., "torsades de pointes"), due to repolarization disturbances of the cardiac action potential. There are far more hERG mutations described for long QT syndrome than for short QT syndrome.
Drug interactions.
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 drug-induced (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).
Although there exist other potential targets for cardiac adverse effects, the vast majority of drugs associated with acquired QT prolongation are 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.
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.
Naming.
The hERG gene was first named and described in a paper by Jeff Warmke and Barry Ganetzky, then both at the University of Wisconsin–Madison. The hERG gene is the human homolog of the "Ether-à-go-go" gene found in the Drosophila fly; "Ether-à-go-go" was named in the 1960s by William D. Kaplan, now at the City of Hope Hospital in Duarte, California. When flies with mutations in the "Ether-à-go-go" gene are anaesthetised with ether, their legs start to shake, like the dancing then popular at the Whisky A Go-Go nightclub in West Hollywood, California.
Interactions.
HERG has been shown to interact with YWHAE.