ABCB11 p.Arg1057*
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PMID: 17181454
[PubMed]
Sakurai A et al: "Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump."
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120
H2N COOH S56L G238V G260D C336S L339V V444A K461E D482G T923P K930X G982R R1090X R1153C Outside Inside R1268Q A1228VE1186K R1128H R1057X R1050C A926P A865V R698H E636G M677V S593R E592Q N591S R575XA570T Q558H I498T R432T R415Q R299K E297G V284A I206V S194P E186G cholestasis Expert Opin. Drug Saf. (2007) 6(1) Table 1.
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ABCB11 p.Arg1057* 17181454:120:130
status: NEW
PMID: 17947449
[PubMed]
Kagawa T et al: "Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells."
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13
The taurocholate transport activity was approximately half of the wild-type (WT) in BRIC2 mutants (A570T and R1050C), was substantially less in two PFIC2 mutants (D482G and E297G), and was almost abolished in six other PFIC2 mutants (K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X).
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ABCB11 p.Arg1057* 17947449:13:283
status: NEW14 Bsep protein expression levels correlated closely with transport activity, except for R1057X.
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ABCB11 p.Arg1057* 17947449:14:86
status: NEW16 BRIC2 mutants and three PFIC mutants (D482G, E297G, and R1057X) were predominantly distributed in the apical membrane.
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ABCB11 p.Arg1057* 17947449:16:56
status: NEW18 The R1057X mutant protein was stably expressed and trafficked to the apical membrane, suggesting that the COOH-terminal tail is required for transport activity but not for correct targeting.
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ABCB11 p.Arg1057* 17947449:18:4
status: NEW19 In conclusion, taurocholate transport function was impaired in proportion to rapid degradation of Bsep protein in the mutants, which were aligned in the following order: A570T and R1050C Ͼ D482G Ͼ E297G Ͼ K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X.
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ABCB11 p.Arg1057* 17947449:19:272
status: NEW165 Other PFIC2 mutants (K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X) did not show significant TC transport activity.
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ABCB11 p.Arg1057* 17947449:165:70
status: NEW168 The E297G mutant was expressed at 16.1 Ϯ 6.8% of that of WT, whereas expression of the other mutants, except for R1057X, was at trace level (Fig. 6, B and C).
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ABCB11 p.Arg1057* 17947449:168:119
status: NEW169 R1057X was expressed as much as was the WT at ϳ120 kDa, which is consistent with the molecular size anticipated after truncated mutant protein.
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ABCB11 p.Arg1057* 17947449:169:0
status: NEW182 TC transport activity was significantly correlated with Bsep protein expression levels when R1057X was excluded from analysis (Fig. 6E, P Ͻ 0.001).
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ABCB11 p.Arg1057* 17947449:182:92
status: NEW184 Subcellular distribution study revealed that E297G, R1057X, A570T, and R1050C mutants were predominantly located along the apical membrane, whereas the other PFIC2 mutants (K461E, G982R, R1153C, R1268Q, and 3767-3768insC) remained intracellular (Fig. 7).
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ABCB11 p.Arg1057* 17947449:184:52
status: NEW187 The R1057X mutant was well expressed and trafficked correctly, but it lacked activity.
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ABCB11 p.Arg1057* 17947449:187:4
status: NEW250 We demonstrated that rapid degradation of Bsep protein is responsible for the defect of TC transport activity with exception of the R1057X mutation.
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ABCB11 p.Arg1057* 17947449:250:132
status: NEW262 Correlation between TC transport activity and Bsep protein expression of WT and mutants Bsep excluding R1057X was tested for significance by Spearman rank correlation.
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ABCB11 p.Arg1057* 17947449:262:103
status: NEW289 Therefore, although the BSEP genotype appears to play an important role in influencing clinical severity, other precipitating factors, including viral infection and pregnancy (37), may participate. In conclusion, our study demonstrates that rapid protein degradation is responsible for decreased TC transport activity in all PFIC2 and BRIC2 mutations except R1057X.
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ABCB11 p.Arg1057* 17947449:289:358
status: NEW290 From the view of maintenance of TC transport activity, the mutants could be aligned in the following order: A570T and R1050C Ͼ D482G Ͼ E297G Ͼ K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X.
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ABCB11 p.Arg1057* 17947449:290:210
status: NEW291 R1057X is expressed stably and localized correctly but loses its activity (defective activity).
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ABCB11 p.Arg1057* 17947449:291:0
status: NEW
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188
Other common mutations include R575X, R1057X, G982R, C336S, R1153C, D482G, K461E, R1153C, R1268Q, R1090X, G238V, S114R, S593R, del 695, and del 3213 (66,67).
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ABCB11 p.Arg1057* 18376240:188:38
status: NEW
PMID: 21219577
[PubMed]
Shimizu H et al: "Living-related liver transplantation for siblings with progressive familial intrahepatic cholestasis 2, with novel genetic findings."
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104
The common mutations include E297G, R575X, R1057X, G982R, C336S, R1153C, D482G, K461E, R1153C, R1268Q, R1090X, G238V, S114R, S593R, del 695 and del 3213 (22).
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ABCB11 p.Arg1057* 21219577:104:43
status: NEW
PMID: 9806540
[PubMed]
Strautnieks SS et al: "A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis."
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101
A second Belgian family (B5) carries the 3169 C→T (R1057X) mutation, and a Polish family (57) carries 908delG, which deletes one base of codon 303, causing a frameshift.
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ABCB11 p.Arg1057* 9806540:101:58
status: NEW142 The ABC transporter family of proteins is the largest so far iden- Table 1• BSEP mutations found in PFIC patients Nucleotide mutation Amino acid number/ Protein consequence Families mutation 1723 C→T R575X Termination codon in first B2 heterozygous nucleotide binding fold Q homozygous 3169 C→T R1057X Termination codon in second B5 heterozygous nucleotide binding fold 908 del G 303 17 novel amino acids then truncation Family 57 heterozygous 3767-3768 ins C 1256 39 novel amino acids then truncation Family 99 homozygous 890 A→G E297G Glutamate to glycine in the intracellular loop S1, S3, S4B, S5, S6, S7, 38 homozygous between transmembrane spans 4 and 5 S4A, B5, B6, B7, 53, L heterozygous 1381 A→G K461E Lysine to glutamate in first Walker A motif Family 55 homozygous 1445 A→G D482G Aspartate to glycine in first P and 52 homozygous nucleotide binding fold 2944 G→A G982R Glycine to arginine in transmembrane span 11 Family 18 homozygous 3457 C→T R1153C Arginine to cysteine in second C and D homozygous nucleotide binding fold 3803 G→A R1268Q Arginine to glutamine in second J homozygous nucleotide binding fold In each case the nucleotide position in the human coding sequence is given along with details of the predicted protein consequence.
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ABCB11 p.Arg1057* 9806540:142:316
status: NEW
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185
PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Missense mutations M1V C336S D549V L1055P E135K E137K T87R V43I S701P G19R W342G G556R C1083Y E137K L198P M123T S56L L712L L50S A382G G562D A1110E E186G E297G S194P Q121K A865D M62K R387H A570T S1114R L198P R415Q L198P R128H A865G C68Y A390P L581F G1116E E297G V444A G260D I206V S874P C107R G410D A588V G1116F G374S D482G E297K V284A I939M I112T L413W S593R G1116R A390P N591S V444A G295C R958Q W114R I420T I627T S1120N R432T T655I T510T G295R F959C Y157C D440E E636G R1128C V444A T655I G295S F959V A167T G455E R698C S1144R I498T D676Y R299K T965S A167V K461E S699P R1153C A570T P710P R303K F971L I182K T463I E709K R1153H T586I L827I L339V F971Y M183T Q466K G758R S1154P G648V G855R H423R L1006F M183V R470Q G766R N1173D T655I E1186K V444A N1009H G188W Y472C Y818F T1210P T923P V444D K1145N M217R V481E R832C N1211D A926P V444G I1183T R223C D482G R832H V1212F R948C A459V S226L R487H T859R R1231Q G1004D I468I G238V R487P A865V R1231W R1050C R487L T242I N490D Q869P L1242I G1116R Q546K A257G I498T G877R D1243G R1128H Q558H V284L G499E S901R R1268Q L1197G E592Q E297G I512T R948C A1283V R1231Q V597M R303G N515T N979D G1292V R616G R303K R517H G982R G1298R T619A Q312H F540L G1004D M677L R313S I541L T1029K M677V G327E I541T G1032R R696Q W330R F548Y A1044P R698H Nonsense mutations (premature stop-codons) S25X Y472X Y772X R1090X E96X W493X Q791X V1147X W330X R520X R928X Q1215X Y354X I528X Y1041X R1235X R415X R575X R1057X E1302X R470X Q702X Q1058X Table 1 (Continued) PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Splice site mutations 76 + 3G > T 908 + 1delG 2178 + 1G > T 3057-2A > G Q159Q 77-1G > C 908 + 1G > T 2179-2A > G 3213 + 1delG Q361Q 99-1G > T 908 + 1G > A 2343 + 1G > T 3213 + 4A > G 150 + 3A > C 1435-13 -8del 2343 + 2T > C 3213 + 5G > A 390-1G > A 2012-8T > G 2611-2A > T 611 + 1G > A 2178 + 1G > A R1001R Deletions/insertions/frame shifts Q101Dfs8X L380Wfs18X G648Vfs5X Q1058Hfs38X F959Hfs1X T127Hfs6X A382 A388del K700Sfs12X I1061Vfs34X F959Gfs48X N199Ifs14X P456Pfs24X T919del L1165del L232Cfs9X H484Rfs5X K930Efs92X A1192Efs50X R303Sfs17X I528Sfs21X K930Efs79X T1256Tfs40X V368Rfs27X I610Qfs45X K969 K972del Synonymous variants without disease association R33R F90F L232L I416I G557G I876I A1028A K1145K D36D I134I Y269Y G418G V597V G937G K1070K R52R S136S Q312Q F427F A804A Y981Y T1086T D58D V195V G319G E395E A535A G817G G1004G A1110A The overview shows ࣈ 290 known variants of BSEP on the protein level, except splice site mutations, which are shown on cDNA level.
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ABCB11 p.Arg1057* 22795478:185:1500
status: NEW