ABCMdb

PMID: 21103971

Stieger B
The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation.
Handb Exp Pharmacol. 2011;(201):205-59., [PubMed]

Sentences

No. Mutations Sentence Comment

411 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly Another interesting finding of this study (Strautnieks et al. 2008) is the observation that the two common E297G and D482G mutants of BSEP varied most in their expression level among the respective carriers. Login to comment 412 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly This is notable, as E297G and D482G variants have been demonstrated to display residual (Noe et al. 2005) or normal (Hayashi et al. 2005a) transport activity, respectively. Login to comment 418 ABCB11 p.Asp482Gly Importantly and interestingly, the common European mutant D482G shows an enhanced aberrant splicing. Login to comment 419 ABCB11 p.Asp482Gly This finding could provide a possible explanation for the wide variation of BSEP expression observed in patients with D482G mutations consequently leading to clinical phenotypes with variable severity. Login to comment 432 ABCB11 p.Asn591Ser Some patients with cholestasis of pregnancy were found to have a novel mutation in the BSEP gene, leading to a p.N591S variant (Dixon et al. 2009; Pauli-Magnus et al. 2004b). Login to comment 439 ABCB11 p.Val444Ala ABCB11 p.Met677Val To date, c.1331T>C (p.V444A) in exon 13 and c.2029A>G (p.M677V) in exon 17 of the BSEP gene are two nonsynonymous SNPs, which consistently have been found with frequencies higher than 0.5% (Lang et al. 2006; Pauli-Magnus et al. 2004a; Saito et al. 2002a; Stieger 2009; Stieger et al. 2007) in different, unrelated cohorts. Login to comment 451 ABCB11 p.Val444Ala Clearly, although the association of a common BSEP variant with increased risk for acquired BSEP deficiency syndromes seems now well established, independent studies with large cohorts are needed to firmly establish the p.V444A polymorphism as a risk factor. Login to comment 472 ABCB11 p.Asp482Gly Interestingly, the D482G mutation reduced transport activity for human BSEP but had no apparent effect on transport when introduced into mouse Bsep (Plass et al. 2004). Login to comment 486 ABCB11 p.Asp482Gly (2008a) D482GReducedsurface expression na G982RNosurfaceexpressionnana R1153CNosurfaceexpressionnana R1286QNosurfaceexpressionnana E297GBSEPMDCKFasterturnoverof ubiquitinatedBSEP fromapical membrane Increased ubiquitination Hayashiand Sugiyama (2009) D482G AdditionalinformationonexpressionofBSEPmutantsisfoundinByrneetal. Login to comment 488 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly (2008) nanotassessed Of note, it was recently demonstrated that levels of the E297G and the D482G mutants of BSEP could be increased at the apical membrane of MDCK cells, if the cells were treated with 4-phenylbutyrate (Hayashi and Sugiyama 2007) or with short-and medium-chain fatty acids (Kato et al. 2010). Login to comment