ABCMdb

ABCB4 p.Arg47Gln

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Publications

PMID: 22331132 [PubMed] Wendum D et al: "Aspects of liver pathology in adult patients with MDR3/ABCB4 gene mutations."

No. Sentence Comment

107 Location and nucleotide change Effect on protein Status of variant Mutation category 1 c.1328dup p.Arg444Glu fsX4, truncating Heterozygous Insertion 2 c.1584 G > C p.Glu528Asp Heterozygous Missense 3 c.101 C > T p.Thr34Met Heterozygous Missense 4 c.1553delT p.Leu518Tyr fsX16, truncating Heterozygous Deletion 5 c.139 C > G p.Arg 47 Gly Heterozygous Missense 6 c.1217 G > A p.Arg 406 Gln Heterozygous Missense c.140 G > A p.Arg47Gln Heterozygous, compound Missense 7 c.857 C > T p.Ala 286 Val Heterozygous Missense 8 c.2324 C > T p.Thr775Met Heterozygous Missense c.2836 G > A p.Ala946Thr Heterozygous Missense 9 c.523A > G p.Thr175Ala Heterozygous Missense 10 c.1005 + 5 G > A p.? Login to comment
106 Location and nucleotide change Effect on protein Status of variant Mutation category 1 c.1328dup p.Arg444Glu fsX4, truncating Heterozygous Insertion 2 c.1584 G > C p.Glu528Asp Heterozygous Missense 3 c.101 C > T p.Thr34Met Heterozygous Missense 4 c.1553delT p.Leu518Tyr fsX16, truncating Heterozygous Deletion 5 c.139 C > G p.Arg 47 Gly Heterozygous Missense 6 c.1217 G > A p.Arg 406 Gln Heterozygous Missense c.140 G > A p.Arg47Gln Heterozygous, compound Missense 7 c.857 C > T p.Ala 286 Val Heterozygous Missense 8 c.2324 C > T p.Thr775Met Heterozygous Missense c.2836 G > A p.Ala946Thr Heterozygous Missense 9 c.523A > G p.Thr175Ala Heterozygous Missense 10 c.1005 + 5 G > A p.? Login to comment

PMID: 21161147 [PubMed] Hopf C et al: "[44-year-old woman with elevated liver enzymes and a family history for cholelithiasis]."

No. Sentence Comment

39 Diskussion LPAC-Syndrom Das LPAC-Syndrom ist gekennzeichnet durch [7]: F eine symptomatische Cholezystolithiasis vor dem 40.Êf;Lebensjahr, Abb. 1ߙ8ߙDie Oberbauchsonographie zeigt intrahepatisch echoreiche Foki, teilweise mit dorsalem Schallschatten (rote Pfeile), ohne intra- oder extrahe- patische Cholestase p.Gly319Glu p.Arg47Gln p.Arg47Gln p.Gly319Glu p.Arg47Gln p.Gly319Glu Keine Mutation Abb. 2ߙ8ߙStammbaum der betroffenen Familie, die Indexpatientin ist mit einem Stern gekennzeichnet. Login to comment

PMID: 26256905 [PubMed] Frider B et al: "Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3."

No. Sentence Comment

71 Site-directed mutagenesis The substitutions R47Q and T82N were introduced into the plasmid pReceiver-M02-MDR3 (Capital Biosciences, Rockville, MD, USA), which contains the full open reading frame of ABCB4, by site-directed mutagenesis using the QuickChange II system (Stratagene, La Jolla, CA, USA). Login to comment
72 Primers used for mutagenesis were as follows (top strand shown; mutated nucleotides are in lowercase): R47Q, 5`-CATTGTT- TCaATACTCCGATTGGC-3`; T82N, 5`-GGAGAGAT- GAaTGACAAATTTG-3`. Login to comment
110 Effects of R47Q and T82N mutations on MDR3 subcellular localization and expression. Login to comment
120 Genetic analysis Sequence analysis revealed that P1 was a compound heterozygote for two missense mutations in exon 4 of ABCB4: c.140G > A and c.245C > A, (p.R47Q and p.T82N respectively; the first of them located in a cytoplasmic domain and the latter in an extracellular domain). Login to comment
123 In vitro studies of ABCB4 mutations In order to determine whether these substitutions affected subcellular localization or expression of MDR3, MDCKII and HEK293T cells were transfected with expression vectors containing wild-type or the mutated versions of MDR3 (R47Q and T82N) and were analyzed by either immunofluorescence or Western blot. Login to comment
127 Thus, R47Q and T82N mutations do not alter MDR3 localization, but lead to reduced protein levels. Login to comment
129 In this disorder, the severity of cholestasis, the time of presentation and the favourable response to UDCA therapy seems to depend on the degree of penetrance of the genetic defect.4,6 The phenotypic characterization of the mutations found in our patient confirms this assumption, since R47Q and T82N do not impair the canalicular expression of MDR3, but they result in a dramatic reduction in the levels of the protein, a finding that correlates with data from the immunohistochemical analysis of the liver biopsy. Login to comment
131 However, it was reported that mutations at R47 impair phosphorylation of N-terminal domain of MDR3, which is determinant for PC secretion.14 It was reported that R47G mutated protein has similar localization and stability to wild-type protein, but PC secretion activity B A KDa 200 150 100 MDR3 Na/K-ATPase Mock WT R47Q T82N Wild-type R47Q T82N resulted markedly decreased because of this lack of phosphorylation of neighboring residues, either Thr44 or Ser49. Login to comment