ABCC7 p.Gly970Ala
| 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] Atomic model of human cystic fibrosis transmembran... Cell Mol Life Sci. 2008 Aug;65(16):2594-612. Mornon JP, Lehn P, Callebaut I
Atomic model of human cystic fibrosis transmembrane conductance regulator: membrane-spanning domains and coupling interfaces.
Cell Mol Life Sci. 2008 Aug;65(16):2594-612., [PMID:18597042]
Abstract [show]
We describe herein an atomic model of the outward-facing three-dimensional structure of the membrane-spanning domains (MSDs) and nucleotide-binding domains (NBDs) of human cystic fibrosis transmembrane conductance regulator (CFTR), based on the experimental structure of the bacterial transporter Sav1866. This model, which is in agreement with previous experimental data, highlights the role of some residues located in the transmembrane passages and directly involved in substrate translocation and of some residues within the intracellular loops (ICL1-ICL4) making MSD/NBD contacts. In particular, our model reveals that D173 ICL1 and N965 ICL3 likely interact with the bound nucleotide and that an intricate H-bond network (involving especially the ICL4 R1070 and the main chain of NBD1 F508) may stabilize the interface between MSD2 and the NBD1F508 region. These observations allow new insights into the ATP-binding sites asymmetry and into the molecular consequences of the F508 deletion, which is the most common cystic fibrosis mutation.
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No. Sentence Comment
254 Indeed, in our CFTR model, substitution of G178 by any other residue results in a steric hindrance with the ICL2 main chain (3.5 between the Ca atoms of G178 and V260), while G970A is the only substitution that might be accommodated without steric incompatibility with ICL4 (4.7 between the Ca atoms of G970 and F1052) (Fig. 7).
X
ABCC7 p.Gly970Ala 18597042:254:182
status: NEW[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.Gly970Ala 8910333:88:4
status: NEW