ABCMdb

ABCC7 p.Thr338Phe

ClinVar:	c.1012A>G , p.Thr338Ala ? , not provided c.1013C>T , p.Thr338Ile D , Pathogenic
CF databases:	c.1013C>T , p.Thr338Ile D , CF-causing ; CFTR1: A nucleotide change C->T at position 1145 which causes the replacement of a Threonine by Isoleucine residue in codon 338 of exon 7. c.1012A>G , p.Thr338Ala (CFTR1) ? , This mutation was identified in one Iranian CBAVD patient.
Predicted by SNAP2:	A: D (85%), C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (53%), K: D (95%), L: D (95%), M: D (95%), N: D (91%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), V: D (85%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: N, P: N, Q: D, R: D, S: N, V: N, W: D, Y: D,

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Publications
[hide] Non-pore lining amino acid side chains influence a... J Physiol. 1998 Oct 1;512 ( Pt 1):1-16. Linsdell P, Zheng SX, Hanrahan JW
Non-pore lining amino acid side chains influence anion selectivity of the human CFTR Cl- channel expressed in mammalian cell lines.
J Physiol. 1998 Oct 1;512 ( Pt 1):1-16., 1998-10-01 [PMID:9729613]

Abstract [show]
1. The effects of individually mutating two adjacent threonine residues in the sixth membrane-spanning region (TM6) of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel on permeation properties were examined using patch clamp recording from mammalian cell lines stably expressing human CFTR. 2. A number of mutations of T338 significantly affected the permeation properties of the channel. Increases and decreases in single channel conductance were observed for different mutants. Anion selectivity was strongly affected, with no two channel variants sharing the same selectivity sequence. Several mutations led to strong inward rectification of the macroscopic current-voltage relationship. The effects of these mutations on permeation properties were correlated with the size of the amino acid side chain substituted, rather than its chemical nature. 3. Most mutations of T339 resulted in a lack of functional channel expression and apparent misprocessing of the protein. One mutant, T339V, was characterized in detail; its permeation properties were significantly altered, although these effects were not as strong as for T338 mutations. 4. These results suggest an important role for T338 in controlling the permeation properties of the CFTR Cl- channel. It is suggested that mutation of this residue alters the interaction between permeating anions and the channel pore via an indirect effect on the orientation of the TM6 helix.

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No. Sentence Comment
59 Stable expression of all six T338 mutants constructed in BHK cells led to the production of both core-glycosylated (band B) and fully glycosylated (band C) CFTR protein, although some mutants (especially T338F) P. Linsdell, S.-X. Zheng and J. W. Hanrahan J. Physiol. 512.12 ) at UNIV OF NORTH CAROLINA on August 8, consistently made less band C protein than wild-type (Fig. 1C). Login to comment
63 In contrast, no currents were activated under these conditions in large inside-out patches excised from BHK cells expressing T338F (n = 8; not shown). Login to comment
118 Thus, the lack of macroscopic Cl¦ currents in membrane patches excised from BHK cells expressing T338F (see above) may reflect a non-conducting phenotype for this mutant. Login to comment
119 Alternatively, misprocessing or degradation of T338F protein (Fig. 1C) may result in expression levels below our threshold of detection using patch clamp recording. Login to comment