Ген KCNQ1 и его роль в развитии синдрома удлиненной QT интервала

Protein coding gene in the species Homo sapiens

Kv7.1 (KvLQT1) is a potassium channel protein whose primary subunit in humans is encoded by the KCNQ1 gene. It's mutation causes Long QT syndrome, Kv7.1 is a voltage and lipid gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among other tissues. In the cardiac cells, Kv7.1 mediates the IKs (or slow delayed rectifying K+) current that contributes to the repolarization of the cell, terminating the cardiac action potential and thereby the heart's contraction. It is a member of the KCNQ family of potassium channels.

KvLQT1 is made of six membrane spanning domains S1 S6, two intracellular domains, and a pore loop. The KvLQT1 channel is made of four KCNQ1 subunits, which form the actual ion channel.

This gene encodes a protein for a voltage gated potassium channel required for the repolarization phase of the cardiac action potential. The gene product can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. The gene is located in a region of chromosome 11 that contains a large number of contiguous genes that are abnormally imprinted in cancer and the Beckwith Wiedemann syndrome. Two alternative transcripts encoding distinct isoforms have been described.

Mutations in the gene can lead to a defective protein and several forms of inherited arrhythmias as Long QT syndrome which is a prolongation of the QT interval of heart repolarization, Short QT syndrome, Currents arising from Kv7.1 in over expression systems have never been recapitulated in native tissues Kv7.1 is always found in native tissues with a modulatory subunit. In cardiac tissue, these subunits comprise KCNE1 and yotiao. Though physiologically irrelevant, homotetrameric Kv7.1 channels also display a unique form of C type inactivation that reaches equilibrium quickly, allowing KvLQT1 currents to plateau. This is different from the inactivation seen in A type currents, which causes rapid current decay.

KvLQT1 has been shown to interact with PRKACA, PPP1CA In addition to associating with KCNE proteins, the N terminal juxtamembranous domain of KvLQT1 can also associate with SGK1, which stimulates the slow delayed potassium rectifier current. Since SGK1 requires structural integrity to stimulate KvLQT1/KCNE1, any mutations present in the KvLQT1 protein can result in reduced stimulation of this channel by SGK1. General mutations in KvLQT1 have been known to cause a decrease in this slow delayed potassium rectifier current, longer cardiac action potentials, and a tendency to have tachyarrhythmias. Mutations in either the alpha subunit of this complex, KvLQT1 or the beta subunit, KCNE1, can lead to Long QT Syndrome or other cardiac rhythmic deformities.