ABCMdb

ABCC7 p.Gly970Glu

ClinVar:	c.2908G>C , p.Gly970Arg D , Pathogenic c.2908G>A , p.Gly970Ser ? , not provided c.2909G>A , p.Gly970Asp D , Likely pathogenic
CF databases:	c.2908G>C , p.Gly970Arg D , CF-causing ; CFTR1: The G970R mutation (G->C at nucleotide position 3040) in exon 15 was found in 1 out of 34 unrelated Belgian CF chromosomes (7 [delta]F508 and 27 non-[delta]F508 CF chromosomes). c.2908G>A , p.Gly970Ser (CFTR1) ? , This mutation was detected by DHPLC analysis followed by direct sequencing. This mutation was found in one CF patient of Egyptian origin who carried the F508 del on the second CF allele c.2909G>A , p.Gly970Asp (CFTR1) ? , The above mutation was found by SSCP/HA in a compound heterozygote; the other mutation is an 8 nt deletion in exon 4. Further patient information will be reported. <BR> (Corrected August 4, 1997)
Predicted by SNAP2:	A: D (80%), C: D (85%), D: D (91%), E: D (95%), F: D (95%), H: D (95%), I: D (91%), K: D (95%), L: D (95%), M: D (91%), N: D (85%), P: D (95%), Q: D (91%), R: D (95%), S: D (80%), T: D (91%), V: D (91%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: 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 novel mutations in a cystic fibrosis patient o... Hum Genet. 1999 Jun;104(6):511-5. Wagner JA, Vassilakis A, Yee K, Li M, Hurlock G, Krouse ME, Moss RB, Wine JJ
Two novel mutations in a cystic fibrosis patient of Chinese origin.
Hum Genet. 1999 Jun;104(6):511-5., [PMID:10453741]

Abstract [show]
Cystic fibrosis is rare in non-Caucasian populations, and in such populations little is known about the spectrum of mutations and polymorphisms in the CFTR gene. We studied a 23-year-old patient of Chinese ethnicity with sweat chloride values of 104 mM/l, pancreatic sufficiency, an FEV1 60% of normal, sputum cultures positive for Staphylococcus aureus and Burkholderia cepacia, and a history of allergic bronchopulmonary aspergillosis. Genetic screening for 31 common CFTR mutations was negative, leading us to search for unknown mutations using single-strand conformation polymorphism and heteroduplex analysis (SSCP/HA). Two novel mutations were detected. In exon 4, a deletion of 8 bp (451458, deltaGCTTCCTA) causes a frameshift and immediately creates a stop codon. In exon 16, mutation 3041G-->A causes the missense change G970D. Functional analysis using an isotopic flux assay indicated that the G970D mutation retains partial function; western blotting indicated that the protein is glycosylated. The patient is heterozygous for the common polymorphisms (2694T/G) in exon 14a and (GATT)6/7 in intron 6a, indicating that these variants arose in ancestors common to Caucasians and Chinese.

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Sentences [show]
No. Sentence Comment
102 Of interest, they found that the peak efflux for the construct G970E was about half that of WT, which is very similar to our result for the natural mutation G970D. Login to comment

[hide] Cytoplasmic loop three of cystic fibrosis transmem... J Biol Chem. 1996 Nov 1;271(44):27493-9. Seibert FS, Linsdell P, Loo TW, Hanrahan JW, Riordan JR, Clarke DM
Cytoplasmic loop three of cystic fibrosis transmembrane conductance regulator contributes to regulation of chloride channel activity.
J Biol Chem. 1996 Nov 1;271(44):27493-9., [PMID:8910333]

Abstract [show]
To examine the contribution of the large cytoplasmic loops of the cystic fibrosis transmembrane conductance regulator (CFTR) to channel activity, the three point-mutations (S945L, H949Y, G970R) were characterized that have been detected in the third cytoplasmic loop (CL3, residues 933-990) in patients with cystic fibrosis. Chinese hamster ovary cell lines stably expressing wild-type CFTR or mutant G970R-CFTR yielded polypeptides with apparent masses of 170 kDa as the major products, whereas the major products of mutants S945L-CFTR and H949Y-CFTR had apparent masses of 150 kDa. The 150-kDa forms of CFTR were sensitive to endoglycosidase H digestion, indicating that these mutations interfered with maturation of the protein. Increased levels of mature CFTR (170 kDa) could be obtained for mutant H949Y when cells were grown at a lower temperature (26 degrees C) or incubated in the presence of 10% glycerol. For all mutants, the open probability (P0) of the CFTR channels was significantly altered. S945L-CFTR and G970R-CFTR showed a severe reduction in the P0, whereas the H949Y mutation doubled the P0 relative to wild-type. The changes in P0 predominantly resulted from an alteration of the mean burst durations which suggests that CL3 is involved in obtaining and/or maintaining stability of the open state. In addition, mutants S945L and G970R had current-voltage relationships that were not completely linear over the range +/-80 mV, but showed slight outward rectification. The fact that CL3 mutations can have subtle effects on channel conductance indicates that this region may be physically close to the inner mouth of the pore.

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Sentences [show]
No. Sentence Comment
89 Introducing a negative charge (G970E) decreased iodide efflux while the introduction of a positive charge (G970K) again abolished CFTR function. Login to comment