ABCC7 p.Leu436Phe
| Predicted by SNAP2: | A: N (87%), C: N (93%), D: N (72%), E: N (82%), F: N (97%), G: N (82%), H: N (97%), I: N (97%), K: N (87%), M: N (97%), N: N (87%), P: N (82%), Q: N (93%), R: N (97%), S: N (87%), T: N (93%), V: N (97%), W: N (93%), Y: N (97%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] A neutral variant involved in a complex CFTR allel... Hum Genet. 2005 May;116(6):454-60. Epub 2005 Mar 3. Clain J, Lehmann-Che J, Girodon E, Lipecka J, Edelman A, Goossens M, Fanen P
A neutral variant involved in a complex CFTR allele contributes to a severe cystic fibrosis phenotype.
Hum Genet. 2005 May;116(6):454-60. Epub 2005 Mar 3., [PMID:15744523]
Abstract [show]
In order to further elucidate the contribution of complex alleles to the wide phenotypic variability of cystic fibrosis (CF), we investigated the structure-function relationships of a severe CF-associated complex allele [p.S912L;p.G1244V]. To evaluate the contribution of each mutation to the phenotype, cystic fibrosis transmembrane conductance regulator (CFTR) mutants were expressed in HeLa cells and analysed for protein processing and Cl- channel activity. Both p.G1244V and [p.S912L;p.G1244V] mutants had normal protein processing but markedly decreased Cl- channel activity compared with wild-type. Notably, the double mutant displayed a dramatic decrease in Cl- channel activity compared with p.G1244V (P<0.001). p.S912L had normal protein processing and no detectable impact on CFTR function. In other respects, the p.S912L variation was identified in compound heterozygosity with p.R709X in a healthy fertile man. Together, these data strongly support the view that p.S912L in isolation should be considered as a neutral variant but one that might significantly impair CFTR function when inherited in cis with another CFTR mutation. Our data also further document the contribution of complex alleles to the wide phenotypic variability of CF. The results of functional studies of such complex alleles in other genetic diseases are discussed.
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No. Sentence Comment
118 The complex allele [p.R201C;p.L436F] has recently been reported (Caciotti et al. 2003); expression studies have revealed a deleterious effect of the p.L436F polymorphism on the known p.R201C mutation resulting in a late infantile subtype of type-II GM1, instead of the juvenile form classically associated with p.R201C.
X
ABCC7 p.Leu436Phe 15744523:118:151
status: NEW