ABCMdb

ABCC7 p.Asp979Glu

ClinVar:	c.2936A>T , p.Asp979Val ? , not provided c.2936A>C , p.Asp979Ala ? , not provided
CF databases:	c.2936A>T , p.Asp979Val (CFTR1) D , The above mutation was detected by DGGE and direct sequencing, and was observed in a French family with 2 CF patients carrying [delta]F508 on their other CF chromosomes. c.2936A>C , p.Asp979Ala (CFTR1) D , D979A was found in a Vietnamese CBAVD patient carrying a yet unknown mutation on the other allele.
Predicted by SNAP2:	A: D (85%), C: D (85%), E: D (80%), F: D (91%), G: D (91%), H: D (91%), I: D (91%), K: D (95%), L: D (91%), M: D (91%), N: D (85%), P: D (91%), Q: D (85%), R: D (91%), S: D (85%), T: D (85%), V: D (91%), W: D (95%), Y: D (91%),
Predicted by PROVEAN:	A: D, C: D, E: D, F: 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: D,

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Publications
[hide] Two mild cystic fibrosis-associated mutations resu... J Biol Chem. 2001 Mar 23;276(12):9045-9. Epub 2000 Dec 15. Clain J, Fritsch J, Lehmann-Che J, Bali M, Arous N, Goossens M, Edelman A, Fanen P
Two mild cystic fibrosis-associated mutations result in severe cystic fibrosis when combined in cis and reveal a residue important for cystic fibrosis transmembrane conductance regulator processing and function.
J Biol Chem. 2001 Mar 23;276(12):9045-9. Epub 2000 Dec 15., 2001-03-23 [PMID:11118444]

Abstract [show]
The number of complex cystic fibrosis transmembrane conductance regulator (CFTR) genotypes identified as having double-mutant alleles with two mutations inherited in cis has been growing. We investigated the structure-function relationships of a severe cystic fibrosis (CF)-associated double mutant (R347H-D979A) to evaluate the contribution of each mild mutation to the phenotype. CFTR mutants expressed in HeLa cells were analyzed for protein biosynthesis and Cl(-) channel activity. Our data show that R347H is associated with mild defective Cl(-) channel activity and that the D979A defect leads to misprocessing. The mutant R347H-D979A combines both defects for a dramatic decrease in Cl(-) current. To decipher the molecular mechanism of this phenotype, single and double mutants with different charge combinations at residues 347 and 979 were constructed as charged residues were involved in this complex genotype. These studies revealed that residue 979, located in the third cytoplasmic loop, is critical for CFTR processing and Cl(-) channel activity highlighting the role of charged residues. These results have also important implications for CF, as they show that two mutations in cis can act in concert to alter dramatically CFTR function contributing to the wide phenotypic variability of CF disease.

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Sentences [show]
No. Sentence Comment
72 Asp-979 was changed to Val (small hydrophobic residue; D979V), Arg (positively charged residue; D979R), or Glu (negatively charged residue; D979E). Login to comment
83 similar to D979A, whereas D979E permitted the complete maturation of the protein (Fig. 1B). Login to comment