KCNQ1

KCNQ1 is a protein-coding gene in humans that encodes the voltage-gated potassium channel subunit Kv7.1, the pore-forming alpha subunit of the IKs channel. The Kv7.1 channel assembles as a tetramer to form the slowly activating delayed rectifier potassium current, IKs, which contributes to the repolarization phase of cardiac action potentials. In cardiac myocytes, IKs helps terminate the action potential, an effect that becomes especially important during increased heart rate or sympathetic stimulation.

Kv7.1 channels interact with regulatory subunits, most notably KCNE1 (minK), which modulates channel kinetics and current amplitude. The Kv7.1/KCNE1 complex is critical for proper repolarization; disruption of this complex can prolong the QT interval on the electrocardiogram.

Mutations in KCNQ1 cause congenital long QT syndrome type 1 (LQTS1), a channelopathy characterized by prolonged QT intervals and an elevated risk of torsades de pointes and sudden cardiac death. In many cases, KCNQ1 mutations contribute to Jervell and Lange-Nielsen syndrome (JLNS), a recessive condition that also includes congenital sensorineural deafness due to impaired inner ear potassium recycling.

Beyond the heart, KCNQ1 is expressed in epithelial tissues, including the inner ear and parts of the gastrointestinal and pancreatic systems, where it participates in potassium transport and homeostasis. Regulation of Kv7.1 involves phosphatidylinositol-4,5-bisphosphate and protein interactions that influence channel gating and trafficking.

Genetic testing for KCNQ1 mutations is used in diagnosing LQTS, guiding management that may include beta-blockers, avoidance of QT-prolonging drugs, and, in high-risk cases, implantable cardioverter-defibrillator therapy.