ABCB4 p.Arg47Gly
| ClinVar: |
c.140G>A
,
p.Arg47Gln
?
, Uncertain significance
|
| Predicted by SNAP2: | A: D (53%), C: D (53%), D: D (80%), E: D (71%), F: D (63%), G: D (66%), H: D (63%), I: D (66%), K: N (87%), L: D (66%), M: N (57%), N: D (63%), P: D (71%), Q: N (78%), S: N (61%), T: N (53%), V: D (63%), W: D (75%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Reversal of advanced fibrosis after long-term urso... Ann Hepatol. 2015 Sep-Oct;14(5):745-51. Frider B, Castillo A, Gordo-Gilart R, Bruno A, Amante M, Alvarez L, Mathet V
Reversal of advanced fibrosis after long-term ursodeoxycholic acid therapy in a patient with residual expression of MDR3.
Ann Hepatol. 2015 Sep-Oct;14(5):745-51., [PMID:26256905]
Abstract [show]
INTRODUCTION: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a severe liver disorder associated with inherited dysfunction of multidrug resistance protein 3 (MDR3/ABCB4), which functions as a phospholipid floppase, translocating phosphatidylcholine from the inner to the outer hemileaflet of the canalicular membrane of hepatocytes. MDR3 deficiency results in a disbalanced bile which may damage the luminal membrane of cells of the hepatobiliary system. We evaluated clinical, biochemical and histological improvement in a genetically proven PFIC-3 patient after long-term ursodeoxycholic acid (UDCA) administration. MATERIAL AND METHODS: A PFIC-3 patient and a relative with cholestatic liver disease were studied. Hepatic MDR3 expression was analyzed by immunohistochemistry and ABCB4 mutations were identified. The effect of the mutations on MDR3 expression and subcellular localization was studied in vitro. RESULTS: A 23-year-old man presented cholestasis with severe fibrosis and incomplete cirrhosis. Canalicular staining for MDR3 was faint. Sequence analysis of ABCB4 revealed two missense mutations that reduce drastically protein expression levels. After 9 years of treatment with UDCA disappearance of fibrosis and cirrhosis was achieved. CONCLUSION: These data indicate that fibrosis associated with MDR3 deficiency can be reversed by long-term treatment with UDCA, at least when there is residual expression of the protein.
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No. Sentence 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.
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ABCB4 p.Arg47Gly 26256905:131:162
status: NEW