Human ether-à-go-go–related gene potassium channel (KCNH2, also called Kv11.1) (hERG)

The human ether-à-go-go–related gene potassium channel (hERG, KCNH2, Kv11.1) is a voltage-gated potassium channel essential for cardiac repolarization by conducting the rapid delayed rectifier potassium current (I_Kr) that shapes the QT interval of the heart’s electrical cycle[1][2][4]. The hERG channel is a tetramer composed of subunits with six transmembrane domains, featuring a unique N-terminal PAS and C-terminal cyclic nucleotide-binding homology domains[4]. It is critically important in preventing arrhythmias: loss or inhibition leads to Long QT syndrome and life-threatening ventricular tachyarrhythmias, while gain-of-function can cause Short QT syndrome[1][2]. hERG is also expressed in the nervous system and certain cancers, where it affects neuronal firing and cell proliferation, respectively[4][5]. Because many drugs can inhibit this channel, leading to fatal arrhythmias, hERG liability is a major concern in pharmaceutical development—making it both a therapeutic and an antitarget[1][2][4].

Other names

hERGKCNH2Kv11.1I_Kr channelEther-à-go-go–related gene potassium channel

Blockade of hERG channels (inhibiting I_Kr current) prolongs the action potential/QT interval - Modulation of channel inactivation/deactivation - Interfering with normal repolarization and increasing arrhythmogenic risk