ABCC7 p.Met348Arg
| ClinVar: |
c.1043T>A
,
p.Met348Lys
?
, not provided
|
| CF databases: |
c.1042A>G
,
p.Met348Val
(CFTR1)
?
, This mutation was identified in a CFTR gene mutation screening of 60 Patients with idiopathic chronic pancreatitis recruited from the region of North Rhine Westfalia in Germany. The entire coding region of the CFTR gene was sequenced.
c.1043T>A , p.Met348Lys (CFTR1) ? , The mutation on the other chromosome is still unknown. This mutation was found on one chromosome while screening 56 Italian CF chromosomes. c.1043T>C , p.Met348Thr (CFTR1) ? , The mutation was detected by DGGE analysis and characterized by direct sequencing. We have seen it only twice, in over 1800 control chromosomes from Italian population. |
| Predicted by SNAP2: | A: D (71%), C: D (66%), D: D (85%), E: D (85%), F: D (63%), G: D (80%), H: D (80%), I: N (53%), K: D (85%), L: N (66%), N: D (71%), P: D (91%), Q: D (63%), R: D (85%), S: D (66%), T: D (75%), V: N (53%), W: D (80%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: N, Y: N, |
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[hide] Corrector VX-809 stabilizes the first transmembran... Biochem Pharmacol. 2013 Sep 1;86(5):612-9. doi: 10.1016/j.bcp.2013.06.028. Epub 2013 Jul 5. Loo TW, Bartlett MC, Clarke DM
Corrector VX-809 stabilizes the first transmembrane domain of CFTR.
Biochem Pharmacol. 2013 Sep 1;86(5):612-9. doi: 10.1016/j.bcp.2013.06.028. Epub 2013 Jul 5., [PMID:23835419]
Abstract [show]
Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis (CF). A potential CF therapy would be to repair CFTR processing mutants. It has been demonstrated that processing mutants of P-glycoprotein (P-gp), CFTR's sister protein, can be efficiently repaired by a drug-rescue mechanism. Many arginine suppressors that mimic drug-rescue have been identified in the P-gp transmembrane (TM) domains (TMDs) that rescue by forming hydrogen bonds with residues in adjacent helices to promote packing of the TM segments. To test if CFTR mutants could be repaired by a drug-rescue mechanism, we used truncation mutants to test if corrector VX-809 interacted with the TMDs. VX-809 was selected for study because it is specific for CFTR, it is the most effective corrector identified to date, but it has limited clinical benefit. Identification of the VX-809 target domain will help to develop correctors with improved clinical benefits. It was found that VX-809 rescued truncation mutants lacking the NBD2 and R domains. When the remaining domains (TMD1, NBD1, TMD2) were expressed as separate polypeptides, VX-809 only increased the stability of TMD1. We then performed arginine mutagenesis on TM6 in TMD1. Although the results showed that TM6 had distinct lipid and aqueous faces, CFTR was different from P-gp as no arginine promoted maturation of CFTR processing mutants. The results suggest that TMD1 contains a VX-809 binding site, but its mechanism differed from P-gp drug-rescue. We also report that V510D acts as a universal suppressor to rescue CFTR processing mutants.
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No. Sentence Comment
178 Examples of typical results obtained with the I344R or M348R mutations introduced into V232D or H1085R are shown in Fig. 5B.
X
ABCC7 p.Met348Arg 23835419:178:55
status: NEW236 (B) Extracts of cells expressing wild-type CFTR or mutants V232D or H1085R with or without the I344R or M348R mutations were subjected to immunoblot analysis.
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ABCC7 p.Met348Arg 23835419:236:104
status: NEW