The latest introduction to the congenital long QT syndrome genes is the LQTS 11 gene AKAP9. A-kinase anchor protein 9 (Yotiao) in humans is encoded by the AKAP9 gene.
Normally cardiac action potential duration shortens during activation of the sympathetic nervous system. This regulation of the cardiac action potential duration mediated by the beta adrenergic receptor activation requires the assembly of AKAP9 with the alpha sub unit (KCNQ1) of the Iks (slow component of delayed rectifier current) potassium channel. A mutation in AKAP9 (Yotiao) in the KCNQ1 binding domain reduces the interaction between KCNQ1 and Yotiao. This in turn reduces the cAMP induced phosphorylation of the channel and prevents the functional response of the Iks channel to cAMP. The final result is prolongation of the action potential and the QT interval due to delayed delpolarization by this S1570L-Yotiao mutation. [Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, Kass RS. Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc Natl Acad Sci U S A. 2007;104:20990-5: http://www.ncbi.nlm.nih.gov/pubmed/18093912 ]