ABCC9 p.Phe1039Ser
| Predicted by SNAP2: | A: D (53%), C: N (61%), D: D (71%), E: D (71%), G: D (66%), H: D (53%), I: D (59%), K: D (53%), L: D (53%), M: N (57%), N: D (59%), P: D (71%), Q: D (53%), R: D (63%), S: D (53%), T: N (53%), V: D (53%), W: D (71%), Y: N (93%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: N, |
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[hide] Dominant missense mutations in ABCC9 cause Cantu s... Nat Genet. 2012 May 18;44(7):793-6. doi: 10.1038/ng.2324. 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
Dominant missense mutations in ABCC9 cause Cantu syndrome.
Nat Genet. 2012 May 18;44(7):793-6. doi: 10.1038/ng.2324., [PMID:22610116]
Abstract [show]
Cantu syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantu syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantu syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantu syndrome.
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No. Sentence Comment
59 The nucleotide-binding Table 1 Summary of detected heterozygous missense mutations in ABCC9 Subject Chr. Genomic alterationa cDNA alteration Protein alteration 9 12 g.22086822C>T c.178C>T p.His60Tyr 7 12 g.22068797C>A c.621C>A p.Asp207Glu 10 12 g.22063786G>T c.1138G>T p.Gly380Cys 5 12 g.22063116C>T c.1295C>T p.Pro432Leu 12 12 g.21998575T>C c.3058T>C p.Ser1020Pro 16 12 g.21997830T>C c.3116>C p.Phe1039Ser 15 12 g.21997785C>A c.3161>A p.Ser1054Tyr 2,3 (child and mother) 12 g.21995374G>A c.3347G>A p.Arg1116His 14 12 g.21995375C>T c.3346C>T p.Arg1116Cys 4 12 g.21995261C>T c.3460C>T p.Arg1154Trp 1,6,8 12 g.21995260G>A c.3461G>A p.Arg1154Gln Chr., chromosome.
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ABCC9 p.Phe1039Ser 22610116:59:396
status: NEW62 a b NBD2 NBD1 TMD2 TMD1 TMD0 p.His60Tyr p.Asp207Glu p.Gly380Cys p.Pro432Leu p.Ser1020Pro p.Phe1039Ser p.Ser1054Tyr p.Arg1116Cys p.Arg1116His p.Arg1116His* p.Arg1154Gln p.Arg1154Gln p.Arg1154Gln p.Arg1154Trp Figure 1 Clinical presentation of subjects with Cant&#fa; syndrome and mutations in ABCC9.
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ABCC9 p.Phe1039Ser 22610116:62:91
status: NEW