Defective ABCC9 (in KCNJ11:ABCC9) does not transport K+ from extracellular region to cytosol

Stable Identifier
R-HSA-5678418
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
22608503 CantĂș syndrome is caused by mutations in ABCC9

van Bon, BW, Gilissen, C, Grange, DK, Hennekam, RC, Kayserili, H, Engels, H, Reutter, H, Ostergaard, JR, Morava, E, Tsiakas, K, Isidor, B, Le Merrer, M, Eser, M, Wieskamp, N, de Vries, P, Steehouwer, M, Veltman, JA, Robertson, SP, Brunner, HG, de Vries, BB, Hoischen, A

Am. J. Hum. Genet. 2012
22610116 Dominant missense mutations in ABCC9 cause CantĂș syndrome

Harakalova, M, van Harssel, JJ, Terhal, PA, van Lieshout, S, Duran, K, Renkens, I, Amor, DJ, Wilson, LC, Kirk, EP, Turner, CL, Shears, D, Garcia-Minaur, S, Lees, MM, Ross, A, Venselaar, H, Vriend, G, Takanari, H, Rook, MB, van der Heyden, MA, Asselbergs, FW, Breur, HM, Swinkels, ME, Scurr, IJ, Smithson, SF, Knoers, NV, van der Smagt, JJ, Nijman, IJ, Kloosterman, WP, van Haelst, MM, van Haaften, G, Cuppen, E

Nat. Genet. 2012
17245405 KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation

Olson, TM, Alekseev, AE, Moreau, C, Liu, XK, Zingman, LV, Miki, T, Seino, S, Asirvatham, SJ, Jahangir, A, Terzic, A

Nat Clin Pract Cardiovasc Med 2007
15034580 ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating

Bienengraeber, M, Olson, TM, Selivanov, VA, Kathmann, EC, O'Cochlain, F, Gao, F, Karger, AB, Ballew, JD, Hodgson, DM, Zingman, LV, Pang, YP, Alekseev, AE, Terzic, A

Nat. Genet. 2004
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
inward rectifier potassium channel activity of ABCC9 mutants:KCNJ11 [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
familial atrial fibrillation 0050650 ATFB
hypertrichosis 420 hypertrichosis NOS (disorder), hypertrichosis (disorder)
osteochondrodysplasia 2256 Unspecified anomaly of cartilage (disorder), chondrodystrophy, Congenital anomaly of cartilage (disorder), Osteochondrodysplasia syndrome (disorder), Cartilage Development disorder
dilated cardiomyopathy 12930 primary dilated cardiomyopathy
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