Meta-Biol

• Pathways

ATP-binding cassette sub-family C member 9 (ABCC9) forms cardiac and smooth muscle-type KATP channels with ATP-sensitive inward rectifier potassium channel 11 (KCNJ11). KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation. Inward rectifier potassium channels favour the flow of potassium into the cell rather than out of it. Defects in ABCC9 can cause dilated cardiomyopathy 10 (CMD10: MIM:608569), a disorder characterised by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Mutations causing CMD10 are L1524Kfs*5 and A1513T (Bienengraeber et al. 2004). Defects in ABCC9 can also cause familial atrial fibrillation 12 (ATFB12; MIM:614050), characterised by disorganized atrial electrical activity and ineffective atrial contraction resulting in blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. A mutation causing ATFB12 is T1547I (Olson et al. 2007). Defects in ABCC9 can also cause hypertrichotic osteochondrodysplasia (Cantu syndrome; MIM:239850), a rare disorder characterised by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia and cardiomegaly. Mutations causing Cantu syndrome include (van Bon et al. 2012, Harakalova et al. 2012).