ABCMdb

PMID: 14662004

Zeitlin PL
Emerging drug treatments for cystic fibrosis.
Expert Opin Emerg Drugs. 2003 Nov;8(2):523-35., [PubMed]

Sentences

No. Mutations Sentence Comment

53 ABCC7 p.Pro574His ABCC7 p.Asn1303Lys The ∆F508 mutation and others such as N1303K or P574H [26], which are also misprocessed in the ER, have been grouped together as Class 2 mutations in CFTR [27]. Login to comment 57 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* Examples in this class include G542X, W1282X, R553X and 621 + 1 G→T. Login to comment 60 ABCC7 p.Gly551Asp ABCC7 p.Gly551Ser This group includes G551D and G551S. Login to comment 61 ABCC7 p.Gly551Asp A lead compound has already been identified that is capable of activating the G551D channel to near wild-type levels, offering the greatest hope for pharmacologic correction. Login to comment 63 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro R117H, R334W and R347P are examples of mutations that appear to yield a milder clinical phenotype even when in combination with a more severe allele. Login to comment 66 ABCC7 p.Ala455Glu Examples of Class 5 mutations include 3849 + 10 kB C→T, A455E or 2789 + 5 G→A. Login to comment 88 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly551Ser ABCC7 p.Gly1349Asp ABCC7 p.Ser1255Pro ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser1455* ABCC7 p.Gln1412Ser Class of mutation Molecular mechanism Pancreatic status (if known) Examples 1 No CFTR protein synthesis PI W1282X, G542X, R553X, 621 + 1 G→T, 1717-1 G→A, 3905insT, 394delTT 2 Abnormal CFTR processing and trafficking PI ∆F508, N1303K, P574H 3 Defective CFTR regulation (normal trafficking) PI G551D, G551S, G1349D, S1255P 4 Decreased CFTR chloride conductance PS R117H, R334W, R347P, P547H 5 Reduced synthesis and trafficking of normal CFTR PS A455E, 3849 + 10kb C→T, (5T) 6A Reduced apical stability PI S1455X, Q1412S, 4326delTC, 4279insA 6B Defective regulation of other ion channels PI G551D Note that the G551D is placed in Class 3 for defective regulation and Class 6B for defective regulation of the outwardly rectifying chloride channel. Login to comment 91 ABCC7 p.Arg117His When 5T is in cis with R117H, there is further reduction in CFTR function. Login to comment 117 ABCC7 p.Gly551Asp Genistein, a tyrosine kinase inhibitor, not only stimulates ∆F508 chloride conductance, but is potent at stimulating the G551D mutant [66-70]. Login to comment 206 ABCC7 p.Gly551Asp Fischer rat thyroid cells stably coexpressing the green fluorescent protein and either wild-type, ∆F508 or G551D CFTR were used to screen 60,000 chemically diverse compounds (at 10 µM) for activation of forskolin-mediated chloride efflux [144,145]. Login to comment 301 ABCC7 p.Pro574His OSTEDGAARD LS, ZEIHER B, WELSH MJ: Processing of CFTR bearing the P574H mutation differs from wild-type and deltaF508-CFTR. Login to comment 416 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp 69. ILLEK B, ZHANG L, LEWIS NC, MOSS RB, DONG JY, FISCHER H: Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am. J. Physiol. Login to comment