Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome

Stable Identifier
R-HSA-5678420
Type
Pathway
Species
Homo sapiens
Synonyms
Defective ABCC9 causes dilated cardiomyopathy 10, familial atrial fibrillation 12 and hypertrichotic osteochondrodysplasia
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome
Click the image above or here to open this pathway in the Pathway Browser
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 (Babenko et al. 1998, Tammaro & Ashcroft 2007). 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.

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 (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 (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 (van Bon et al. 2012, Harakalova et al. 2012).
Literature References
PubMed ID Title Journal Year
22610116 Dominant missense mutations in ABCC9 cause Cantú syndrome

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

Nat. Genet. 2012
22608503 Cantú syndrome is caused by mutations in ABCC9

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

Am. J. Hum. Genet. 2012
17855752 A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit

Ashcroft, FM, Tammaro, P

J. Physiol. (Lond.) 2007
17245405 KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation

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

Nat Clin Pract Cardiovasc Med 2007
9831708 Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells

Bryan, J, Gonzalez, G, Aguilar-Bryan, L, Babenko, AP

Circ. Res. 1998
15034580 ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating

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

Nat. Genet. 2004
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
hypertrichosis DOID:420 hypertrichosis NOS (disorder), hypertrichosis (disorder)
familial atrial fibrillation DOID:0050650 ATFB
osteochondrodysplasia DOID:2256 Unspecified anomaly of cartilage (disorder), chondrodystrophy, Congenital anomaly of cartilage (disorder), Osteochondrodysplasia syndrome (disorder), Cartilage Development disorder
dilated cardiomyopathy DOID:12930 primary dilated cardiomyopathy
Authored
Jassal, B  (2015-02-24)
Reviewed
Moitra, K  (2015-04-28)
Created
Jassal, B  (2015-02-24)
Cite Us!