ABCMdb

ABCC7 p.Gln98Ala

ClinVar:	c.293A>G , p.Gln98Arg ? , not provided c.292C>T , p.Gln98* D , Pathogenic c.293A>C , p.Gln98Pro ? , not provided
CF databases:	c.293A>C , p.Gln98Pro (CFTR1) D , This mutation was found by DHPLC and confirmed by sequencing. The adult male patient, from Southern Sweden, carries deltaF508 on the other chromosome. The patient has high sweat chloride (116 mmol/L), bronchiectasis and CBAVD. c.292C>T , p.Gln98* D , CF-causing c.293A>G , p.Gln98Arg (CFTR1) D , This mutation was found in one CF patient from Southern France, who carries [delta]F508 on the other gene. It creates a HaeIII restriction site (N : 290 +78 +70 bp), (m: 153 + 137 + 78 + 70 bp) when using the primers 4i5/4i3 from Zielinski. Also reported by Yoshimura & Azuma on 4/01/1000: This mutation was detected in one of the CFTR alleles of a 15-year old Japanese male patient with cystic fibrosis. He is pancreatic insufficient, has CBAVD, and his sweat chloride was high (74 mmol/L). Another mutation was not found despite the thorough evaluation for his entire 27 exons of the CFTR gene. Interestingly, he was heterozygous at the cDNA 125 in 5'UTR (i.e., 125G/125C), and this is the only difference from his healthy sister who is also heterozygous for Q98R mutation, but 125G/125G, suggesting that 125C may be disease-causing.
Predicted by SNAP2:	A: D (95%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), R: N (78%), S: D (95%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: N, P: D, R: N, S: N, T: D, V: D, W: D, Y: D,

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[hide] Direct comparison of the functional roles played b... J Biol Chem. 2004 Dec 31;279(53):55283-9. Epub 2004 Oct 25. Ge N, Muise CN, Gong X, Linsdell P
Direct comparison of the functional roles played by different transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore.
J Biol Chem. 2004 Dec 31;279(53):55283-9. Epub 2004 Oct 25., 2004-12-31 [PMID:15504721]

Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel contains 12 transmembrane (TM) regions that are presumed to form the channel pore. However, little is known about the relative functional contribution of different TM regions to the pore. We have used patch clamp recording to investigate the functional consequences of point mutations throughout the six transmembrane regions in the N-terminal part of the CFTR protein (TM1-TM6). A range of specific functional assays compared the single channel conductance, anion binding, and anion selectivity properties of different channel variants. Overall, our results suggest that TM1 and -6 play dominant roles in forming the channel pore and determining its functional properties, with TM5 perhaps playing a lesser role. In contrast, TM2, -3, and -4 appear to play only minor supporting roles. These results define transmembrane regions 1 and 6 as major contributors to the CFTR channel pore and have strong implications for emerging structural models of CFTR and related ATP-binding cassette proteins.

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Sentences [show]
No. Sentence Comment
76 However, the unitary conductance was drastically reduced by some mutations in TM1 (K95Q, Q98A, P99A) and TM6 (R334K, F337A) (Figs. 2-4). Login to comment
82 In most cases macroscopic I-V relationships were linear or weakly inwardly rectifying in the presence of symmetrical high Cl- concentra- tions (as quantified in Fig. 6), although particularly strong inward rectification was observed in Q98A, P99A, and R334K. Login to comment
102 The weakest block by Au(CN)2 - was observed in K95Q, T338A, R334K, and Q98A, consistent with these residues perhaps being associated with permeant anion binding sites inside the pore. Login to comment
119 Some mutants that significantly affect both unitary conductance and Au(CN)2 - block were found to be without effect on SCN- permeability (Q98A, V318A, R334K, K335A). Login to comment