Potassium voltage-gated channel subfamily H member 2 (hERG) (hERG)

The rapid component of the delayed rectifier potassium current, commonly known as IKr, is a fundamental ionic current essential for the terminal repolarization of the cardiac action potential in humans. This current is primarily conducted by the Potassium voltage-gated channel subfamily H member 2, which is encoded by the KCNH2 gene and frequently referred to as the human Ether-à-go-go-Related Gene (hERG) (UniProt: P51787). Proper functioning of this channel is vital for maintaining a normal heart rhythm, as it facilitates the efflux of potassium ions from myocytes to end the electrical impulse (StatPearls: Long QT Syndrome). Mutations in KCNH2 that cause a loss of function lead to Long QT Syndrome Type 2 (LQTS2), a condition characterized by delayed repolarization and a high risk of life-threatening ventricular arrhythmias (PubMed: 11518974). In the pharmaceutical industry, the hERG channel is a major safety concern because many structurally diverse drugs can unintentionally block the channel's pore (ICH S7B Guidelines). Consequently, unintended hERG inhibition is a leading cause of drug attrition and post-marketing withdrawals, making hERG screening a mandatory regulatory requirement in modern drug discovery.

Other names

KCNH2hERGKv11.1Human Ether-à-go-go-Related GeneERG1Rapidly activating delayed rectifier potassium channel

Drugs typically act as pore blockers of the hERG channel, binding to specific residues within the large inner cavity and physically obstructing the outward flow of potassium ions. This inhibition reduces the repolarizing current (IKr), thereby lengthening the cardiac action potential duration and the QT interval on an electrocardiogram.