Pathway
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome
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 favor the flow of potassium into the cell rather than out of it. KATP channels open and close in response to intracellular changes in the ADP/ATP ratio, thereby linking the metabolic state of the cell to its membrane potential. Inhibition of KATP channel activity causes membrane depolarization and thereby activation of voltage-dependent Ca2+ channels, leading to Ca2+ influx and a rise in intracellular Ca2+ concentration. Correct maintenance of calcium balance is essential for the normal functioning of the heart.
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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. 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. 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 (van Bon et al. 2012, Harakalova et al. 2012).
What the reference databases state
Statements
2 statements
2 statements · 1 reference database · Subject: Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome · Sources: Reactome
- ABCC9 participates in Defective ABCC9 causes CMD10, ATFB12 and Cantu syndromeProteinReactome R-HSA-5678420Inferred only
- KCNJ11 participates in Defective ABCC9 causes CMD10, ATFB12 and Cantu syndromeProteinReactome R-HSA-5678420Inferred only