ABCC7 p.Gly970Met
| 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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[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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No. Sentence Comment
88 The G970A and G970M alterations resulted in efflux levels similar to wild-type, suggesting that amino acid size was not the major factor determining disturbance of CFTR function.
X
ABCC7 p.Gly970Met 8910333:88:14
status: NEW