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Human ether-a-go-go related gene (HERG) encodes the pore-forming subunit of the delayed rectifier potassium channel IKr. There are two N-terminal splice variants of HERG include the full-length isoform 1 alpha and the shorter isoform 1 beta. Isoform 1 beta lacks the PAS motif and deactivates at a faster rate than isoform 1alpha. Residues within the C-terminal play a role in channel expression and channel gating, including voltage-dependent activation. HERG is expressed in the heart and is more abundantly expressed in the ventricles than in the atria. Mutations in the gene encoding HERG increase beat-to-beat variability and early after depolarization. These fluctuations facilitate the genesis and propagation of premature heartbeats associated with inheritable long QT syndrome type 2 and short QT syndrome type 1.
