ABCC7 p.Asn369*
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[hide] CFTR! Am J Physiol. 1992 Aug;263(2 Pt 1):C267-86. Fuller CM, Benos DJ
CFTR!
Am J Physiol. 1992 Aug;263(2 Pt 1):C267-86., [PMID:1381146]
Abstract [show]
Cystic fibrosis (CF) is a fatal genetic disease primarily affecting Caucasians, although cases have been reported from other ethnic groups. CF has a complex etiology, but it is chiefly a disease of electrolyte transport and is characterized by defects in fluid secretion by several epithelia, including the sweat duct, exocrine pancreas, and the pulmonary airways. The link between CF and a defect in cAMP-mediated Cl- transport in secretory epithelia was established in the early 1980s. Since then, numerous electrophysiological studies have focused on the characterization and regulation of individual Cl- channels underlying the macroscopic Cl- currents of secretory epithelia in the airways, sweat ducts, and gut. In this review the results of these studies in the light of current knowledge of the function of the CF gene product, the CF transmembrane conductance regulator (CFTR) protein, will be analyzed. The CFTR protein is a member of a family of ATP-binding proteins that act as unidirectional solute pumps. These proteins are membrane spanning, are found in both prokaryotic and eukaryotic cells, and have two ATP-binding domains. The family includes the p-glycoproteins that are involved with the expression of multidrug resistance in certain tumor cells. The majority of CF chromosomes (70%) have a single codon deletion that translates to a missing phenylalanine residue at position 508 (delta F508) of the protein. Unique for this family of proteins, the CFTR protein possesses an additional highly charged domain (the R domain) containing several consensus polypeptide sequences for kinase phosphorylation. Although CFTR bears structural resemblance to this family of ATP-dependent pumps, overexpression of the protein in a variety of different cell types is associated with the appearence of a cAMP-sensitive Cl- channel. We critically examine current information concerning the structure-function relationships of the CFTR protein obtained from both electrophysiological and biochemical approaches. We also summarize recent evidence suggesting that the CFTR protein may act as a pump and a channel, a hypothesis in keeping with the multifaceted nature of the disease.
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No. Sentence Comment
225 Hence N369X is the change of an asparagine at residue position 369 to a termination codon, which should lead to a prematurely shortened protein.
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ABCC7 p.Asn369* 1381146:225:6
status: NEW366 AF508/AF508 G551D/G551D G542X/G458V G542X/G542X R553X/W1316X N369X/unknown R553X/R553X G551S/G551S G368Xlunknown AF508/R117H PI PI PI PI PI PI PI PS PS PS Severe 116 Severe 181 Severe 49 Mild 49 Mild 50 Mild 102 Moderate-Severe 13 Mild 181 Mild 102 Mild 55 Comparison of genotype with phenotype for some CF-associated mutations.
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ABCC7 p.Asn369* 1381146:366:61
status: NEW420 In another case, a frame shift caused the introduction of a stop codon at amino acid residue 369 (N369X), which falls between TM6 and the first NBF.
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ABCC7 p.Asn369* 1381146:420:98
status: NEW425 However, an individual who is translating an mRNA lacking the first NBF region altogether (AF508, N369X) would appear to be better off than one who is homozygous for AF508.
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ABCC7 p.Asn369* 1381146:425:98
status: NEW