ABCMdb

PMID: 11966405

Sangiuolo F, D'Apice MR, Bruscia E, Lucidi V, Novelli G
Towards the pharmacogenomics of cystic fibrosis.
Pharmacogenomics. 2002 Jan;3(1):75-87., [PubMed]

Sentences

No. Mutations Sentence Comment

107 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* G542X 621 + 1 G→→→→T 3905insT W1282X R553X 1717 - 1 G→→→→A PI Lack of CFTR biosynthesis or defective biosynthesis producing abnormal protein variants. Login to comment 111 ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Asn1303Lys Gentamicin Neomicin (G418) Class II Mutations that fail to be properly processed to a matureglycosylatedform and transported to the apical membrane ∆F508 N1303K P574H A455E PI Defective CFTR processing and trafficking. Login to comment 113 ABCC7 p.Gly551Asp ABCC7 p.Gly551Ser G551D G551S PI Defective chloride channel Regulation Reduced or absent cell surface chloride transport Genistein Pyrophosphate UTP INS36217 Moli1901 Class IV Mutations located within membrane spanning domain, implicated in forming the pore of the channel. Login to comment 114 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly314Glu R117H R334W G314E R347P ∆F508 P574H PS Reduced chloride conductance Reduced levels of cell surface chloride transport Genistein Milrinone Phenylbutyrate UTP INS36217 Moli1901 Class V Mutations causing defects in CFTR channel expression levels. Login to comment 115 ABCC7 p.Ala455Glu 3849 + 10 kb C→→→→T 2789 + 5 G→→→→A 3272-26 A→→→→G A455E 3120 +1 G→→→→A 1811 + 1.6 kb A→→→→G 5T PS Normal CFTR channnels Reduced numbers of normal CFTR Reduced cell surface chloride transport Genistein Milrinone Phenylbutyrate Class VI Nonsense or frameshift mutations causing a 70-100 bp truncation of the C-terminus of the CFTR mutations that impair regulation of other types of ion channels. Login to comment 116 ABCC7 p.Gln1412* Q1412X, 4326delTC, 4279insA Severe Functional but unstable CFTR at the apical membrane See text Modified from [56,102]. Login to comment 156 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* G542X, 621+1 G→T, W1282X and R553X belong to the class I group of mutations. Login to comment 174 ABCC7 p.Gly551Asp In vitro investigations have demonstrated an increased production of mature CFTR and chloride transport at the cell surface for both wild type, ∆F508 and G551D, by a mechanism that involves upregulation at the transcriptional level and modulation of protein folding steps [47]. Login to comment 184 ABCC7 p.Gly551Asp Genistein has also been shown to restore G551D function (class III mutation) [54]. Login to comment 186 ABCC7 p.Gly551Asp ATP binding and phosphorylation to G551D are severely affected but can be overcome by interaction with flavonoids. Login to comment 190 ABCC7 p.Arg117His The somministration of adenosine and its nucleotides can activate wild type and R117H forms of CFTR in cell cultures binding to the A2B receptor, present in human bronchial epithelium [55]. Login to comment 445 ABCC7 p.Gly551Asp Illek B, Zhang L, Lewis NC, Moss RB, Dong JY, Ficsher H: Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Login to comment 448 ABCC7 p.Arg117His 55. Clancy JP, Ruiz FE,Sorscher EJ: Adenosine and its nucleotides activate wild-type and R117H CFTR through an A2B receptor-coupled pathway. Login to comment 450 ABCC7 p.Arg117His •• This study indicates that adenosine and its nucleotides are capable of activating wild type CFTR-dependent halide permeability and also R117H mutant CFTR molecules. Login to comment