ABCMdb

ABCB11 p.Arg1153Cys

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Publications

PMID: 12663868 [PubMed] Trauner M et al: "Bile salt transporters: molecular characterization, function, and regulation."

No. Sentence Comment

631 G238V, E297G, G982R, R1153C, and R1268Q mutations prevent the protein from trafficking to the apical membrane, whereas the G238V mutant seems to be rapidly degraded by proteasomes. Login to comment

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."

No. Sentence Comment

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. Login to comment
131 - 25 3383 G→A Arg1128His BRIC2 [45] - 25 3457 C→T Arg1153Cys PFIC2 [35] rs1521808 26 3556 G→A Glu1186Lys - [102] - 26 3683 C→T Ala1228Val - [44] - 27 3767 - 3768 X→C Frame shift at position 1256 PFIC2 [35] - 27 3803 G→A Arg1268Gln PFIC2 [35] Intron 4 3 A→C - PFIC2 [43] Table 2. Login to comment

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."

No. Sentence Comment

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). Login to comment
19 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. Login to comment
139 The positions of 8 PFIC2 mutations (E297G, K461E, D482G, G982R, R1057C, R1153C, 3767-3768insC, and R1268Q) and 2 BRIC2 mutations (A570T and R1050C) are indicated by ଝ and ଙ, respectively. Login to comment
165 Other PFIC2 mutants (K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X) did not show significant TC transport activity. Login to comment
184 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). Login to comment
188 Other PFIC2 mutant proteins (K461E, G982R, R1153C, R1268Q, and 3767-3768insC) were unstable and lost all transport activity. Login to comment
245 The mature form of Bsep protein (band C) of K461E, G982R, R1153C, R1268Q, and 3767-3768insC mutants was hardly detected (Fig. 6B) and, consequently, TC transport activity was abolished (Fig. 6A). Login to comment
290 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. Login to comment

PMID: 18376240 [PubMed] Alissa FT et al: "Update on progressive familial intrahepatic cholestasis."

No. Sentence Comment

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). Login to comment

PMID: 18798335 [PubMed] Wang L et al: "Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II."

No. Sentence Comment

4 G238V, D482G, G982R, R1153C, and R1286Q all retain Bsep to the endoplasmic reticulum (ER) to different extents. Login to comment
5 Except for R1153C, the PFIC II mutants are degraded with varying half-lives. Login to comment
12 These data together demonstrate that the PFIC II mutants except R1153C and ⌬Gly are degraded by the ERAD pathway. Login to comment
48 The following missense mutants were studied in this work: G238V, D482G, G982R, R1153C, and R1286Q. Login to comment
82 The positions of G238V, D482G, G982R, R1153C, and R1286Q are indicated by star signs in a predicted topology model of rat Bsep. Login to comment
95 As can be seen, there is substantial colocalization between GFP-Bsep and calnexin in mutants that are exclusively core-glycosylated or non-glycosylated, that is, G982R, R1153C, R1286Q, and ⌬Gly. Login to comment
119 G982R, R1286Q, and ⌬Gly were degraded over time as indicated by the decrease in the core-glycosylated form (the only form detected), whereas R1153C was relatively stable. Login to comment
123 R1153C is relatively stable. Login to comment
246 Taken together, the data from this study show that G238V, D482G, G982R, R1153C, R1286Q, and ⌬Gly mutations cause retention of Bsep in the ER to different extents. Login to comment
249 Except for R1153C, the PFIC II mutants are short-lived, displaying distinct half-lives as measured by both cycloheximide chase and pulse-chase analyses. Login to comment
274 R1153C is an interesting mutant, in that it is stable yet retained in the ER. Login to comment
275 The R1153C Bsep protein resembles two mutants of the yeast a-factor transporter Ste6p, Ste6- 13p, and Ste6-90p, which are retained in the ER and are hyperstable.24 In contrast, a large number of Ste6 mutants, such as Ste6-166p, are highly unstable and are degraded by the ERAD pathway. Login to comment
277 The R1153C mutant might be an example of this latter mechanism. Login to comment
278 R1153C most likely adopts a misfolded, bile salt transport-inactive conformation, because the mutant protein fails to transport taurocholate when expressed in Sf9 membrane vesicles.8 The misfolded R1153C is thus retained in the ER for continued folding attempts or sequestration instead of being degraded by the ERAD pathway. Login to comment

PMID: 19101985 [PubMed] Byrne JA et al: "Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing."

No. Sentence Comment

68 Continued Exon Nucleotide Change Predicted Protein Effect Location in Protein Associated Phenotype Prevalence or frequency* Any Defect(s) Identified Reference BRIC, 1 family (both hom) 15 c.1757CϾT T586I Adj WB BRIC 1 family (het) No splicing † 15 c.1763CϾT A588V Adj WB PFIC 2 families (both het) No protein 31, 32 15 c.1772AϾG N591S Adj WB SNP-ICP 2.6% 42 15 c.1779TϾA S593R NBF1 PFIC 1 family (het) 29 15 c.1791GϾT V597V NBF1 SNP 2.6% 42 16 c.1880TϾC I627T IC3 PFIC 1 family (het) ‡ 16 c.1964CϾT T655I IC3 BRIC / ICP / DC 1 family (het) Reduced levels of mature protein ‡ 17 c.2029AϾG M677V IC3 SNP 1.6-5.6% 39, 42-45 18 c.2093GϾA R698H IC3 SNP 0.3 - 0.8% 43, 45 18 c.2125GϾA E709K IC3 SNP-PFIC 1 family (het) ‡ 18 c.2130TϾC P710P IC3 SNP-PBC 0.5 - 3.1% 43 20-21 c.2412AϾC A804A TM8 SNP 1.1% 45 20-21 c.2453AϾT Y818F IC4 SNP-PFIC 2 families (hom) Reduced levels of mature protein ‡ 20-21 c.2494CϾT R832C IC4 PFIC 2 families (1 het, 1 consanguineous) Moderate differential splicing 31, 32 20-21 c.2576CϾG T859R IC4 PFIC 1 family (het) 31 22 c.2767AϾC T923P IC5 BRIC 1 family (het) 8 22 c.2776GϾC A926P IC5 BRIC 1 family (het) Mild exon skipping 8 23 c.2842CϾT R948C IC5 PFIC 2 families (both het) Immature protein 31 23 c.2935AϾG N979D TM11 PFIC 1 family (consanguineous) 31 23 c.2944GϾA G982R TM11 PFIC 4 families (1 hom, 1 consanguineous, 2 het) Immature protein 7, 29, 31 23 c.3011GϾA G1004D EC6 PFIC 1 family (hom) 28 24 c.3084AϾG A1028A TM12 SNP-PBC 39.86 - 56.3% Severe exon skipping 8, 43, 45 24 c.3148CϾT R1050C C term BRIC 2 familes (1 hom, 1 het) Immature protein 8 25 c.3329CϾA A1110E Adj WA PFIC 2 familes (both het) Mild exon skipping; immature protein 31 25 c.3346GϾC G1116R WA PFIC / BRIC 1 family (consanguineous) Mild exon skipping ‡ 25 c.3382CϾT R1128C NBF2 PFIC 1 family (consanguineous) Mild exon skipping; immature protein 31 25 c.3383GϾA R1128H NBF2 BRIC 1 family (hom) Mild exon skipping; greatly reduced levels of mature protein 8 26 c.3432CϾA S1144R NBF2 PFIC 1 family (het) Severe differential splicing 29 26 c.3457CϾT R1153C NBF2 PFIC 4 families (2 consanguineous, 2 het) Immature protein 7, 31, 36 26 c.3458GϾA R1153H NBF2 PFIC 4 families (2 consanguineous, 2 het) Severe differential splicing; immature protein 31 26 c.3460TϾC S1154P NBF2 PFIC 1 family (het) Severe differential splicing 31 26 c.3556GϾA E1186K NBF2 SNP 1%-10% Mild exon skipping ‡ 26 c.3589_3590 delCTinsGG L1197G NBF2 BRIC 1 family (het) † 27 c.3628AϾC T1210P Adj ABCm PFIC 1 family (hom) Immature protein 31 27 c.3631AϾG N1211D Adj ABCm SNP-PFIC 1 family (het) ‡ 27 c.3669GϾC E1223D ABCm Prolonged NNH 1 family (het) ‡ 27 c.3683CϾT A1228V Adj ABCm/WB SNP-PBC 0.8% 43 27 c.3691CϾT R1231W Adj ABCm/WB PFIC 1 family (het) Severe exon skipping; immature protein 30, 31 27 c.3692GϾA R1231Q Adj ABCm/WB PFIC 2 families (1 consanguineous, 1 het) No splicing; immature protein 31, 34 27 c.3724CϾA L1242I WB PFIC 1 family (het) 31 28 c.3892GϾA R1268Q¶ NBF2 PFIC 1 family (hom) Immature protein 7 *Prevalence or frequency is quoted depending on how data were presented in the original publication(s). Login to comment

PMID: 20010382 [PubMed] Ho RH et al: "Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability."

No. Sentence Comment

138 Functional analysis of bile salt export pump variants A panel of expression plasmids comprising wild-type BSEP, nine nonsynonymous BSEP variants, and two known PFIC2 BSEP missense mutants, 2944G > A (Gly982Arg) and 3457C >T (Arg1153Cys), was constructed for functional studies. Login to comment

PMID: 20232290 [PubMed] Davit-Spraul A et al: "ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history."

No. Sentence Comment

104 14b† p.I420T p.I1061VfsX34 na na PFIC2 no. 15*,‡ p.A167T p.G1058HfsX38 0.5 BSEP À PFIC2 no. 16* p.R1231W p.I528X na na PFIC2 no. 17 p.M62K p.I112T þ p.R698H 0.10 BSEP À PFIC2 no. 18* p.E297G p.H484RfsX5 0.16 BSEP À PFIC2 no. 19* p.E297G p.I610GfsX45 0.23 BSEP À PFIC2 no. Login to comment
107 24† p.R1153C c.3213 14 A>G 0.13 BSEP À PFIC2 no. 25* p.G982R p.Q101DfsX8 0.10 BSEP À PFIC2 no. 26* p.N591S þ p.V597V nf 0.39 BSEP À PFIC2 no. 27* p.G982R p.R1001R na BSEP À PFIC2 no. 28 p.L232CfsX9 nf na BSEP À PFIC2 no. 29 p.W114R nf 0.50 BSEP À PFIC2 no. Login to comment

PMID: 20422495 [PubMed] Lam P et al: "The bile salt export pump: clinical and experimental aspects of genetic and acquired cholestatic liver disease."

No. Sentence Comment

77 Ubiquitylation is involved in the degradation of receptors, channels, and transporters from the endoplasmic reticulum and cell surface of yeast and higher eukaryotes.86-88 Wang et al, showed for the first time that specific E3 ubiquitin ligases are involved in Bsep degradation.58 Bsep mutants (p.G238V, p.D482G, p.G982R, p.R1153C, and p.R1268Q) were highly ubiquitinated following overexpression of different E3 ubiquitin ligases and were rapidly degraded by proteasomes resulting in shorter half-lives compared with the wild-type protein.58 This study suggests that stabilizing aberrant BSEP proteins by inactivating key E3 ubiquitin ligases might be a novel therapeutic approach, providing that global effects on proteasomal degradation can be avoided. Login to comment

PMID: 21219577 [PubMed] Shimizu H et al: "Living-related liver transplantation for siblings with progressive familial intrahepatic cholestasis 2, with novel genetic findings."

No. Sentence Comment

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). Login to comment

PMID: 9806540 [PubMed] Strautnieks SS et al: "A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis."

No. Sentence Comment

122 The mutation 3457 C→T (R1153C) is present in a further two Saudi Arabian families and replaces a conserved arginine with a cysteine in the second nucleotide binding fold. One family of Kuwaiti origin carries 3803 G→A (R1268Q), which predicts replacement of arginine with glutamine in the second nucleotide binding fold. One or more of these mutations have been found in 25 PFIC families. Login to comment
142 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. Login to comment
163 Two consanguineous families of Saudi Arabian Bedouin origin which are not known to be related, but share the same family name, carry 3457 C→T (R1153C). Login to comment
236 The endonucleases used were: HphI (E297G), BpmI (K461E), FokI (D482G), AlwNI (G982R), BsrBI (R1153C) and AvaII (R1268Q). Login to comment

PMID: 20103563 [PubMed] Klaassen CD et al: "Xenobiotic, bile acid, and cholesterol transporters: function and regulation."

No. Sentence Comment

6508 Nucleotide Change Amino Acid Change In Vitro Function Protein Expression/ Localization ABCB11 BSEP N.D. G238V N.D. Intracellular A890G E297G 2 Intracellular N.D. C336S ↔ Normal G1296C R432T 2 Reduced T1331C V444A ↔ Normal/Reduced A1445G D482G 2 Normal/Reduced G2026T D676Y 2 Reduced G2563A G855R 2 Reduced G2944A G982R 2 Intracellular C3457T R1153C 2 Intracellular G3803A R1268Q 2 Intracellular searchers were able to identify functional roles for Mrp2 using rats lacking this transporter (Eisai hyperbilirubinemic rats on a Sprague-Dawley background and transport-deficient (TR-) on a Wistar background) (Paulusma et al., 1996; Ito et al., 1997). Login to comment

PMID: 17241866 [PubMed] Liu C et al: "Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis."

No. Sentence Comment

70 Diagnosisa Mutation 1 ␣1AT deficiency SERPINA1 T638C (Val213Ala, homozygous) and G1024A (Glu342Lys, homozygous)45,46 2 ␣1AT deficiency SERPINA1 T638C (Val213Ala, homozygous) and G1024A (Glu342Lys, homozygous)45,46 3 ␣1AT deficiency SERPINA1 T638C (Val213Ala, homozygous) and G1024A (Glu342Lys, homozygous)45,46 4 Alagille syndrome JAG1 C2230T (Arg744stop, heterozygous)47 5 Alagille syndrome JAG1 IVS19 ϩ1 G to A, heterozygous48 6 Alagille syndrome JAG1 C2650T (Glu884Stop, heterozygous)b 7 Alagille syndrome JAG1 C2650T (Glu884Stop, heterozygous)b 8 PFIC1 ATP8B1 C2788T (Arg930stop, heterozygous)28 9 PFIC1 ATP8B1 T1982C (Ile661Thr, heterozygous)15 10 PFIC1 ATP8B1 569-base pair deletion (including first 17 base pairs in exon 23, homozygous)b 11 PFIC2 ABCB11 C3457T (Arg1153Cys, heterozygous)17 12 PFIC2 ABCB11 C2782T (Arg928Stop, heterozygous)b 13 PFIC3 ABCB4 A874T (Lys292Stop, homozygous) and A1954G (Arg652Gly, homozygous)49 14 Biliary atresia ATP8B1 IVS 26 ϩ8 G to T, heterozygousb 15 Biliary atresia No nonsynonymous polymorphism 16 Biliary atresia No nonsynonymous polymorphism 17 Biliary atresia JAG1 C2612G (Pro871Arg, heterozygous)50 18 Biliary atresia SERPINA1 G302A (Arg101His, heterozygous)51 NOTE. Login to comment

PMID: 16180115 [PubMed] Ito K et al: "Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport."

No. Sentence Comment

240 Seven amino acid substitutions in BSEP, linked to PFICII (G238V, E297G, C336S, D482G, G982R, R1153C, R1268Q), have been reported and have been examined using rat Bsep expressed in MDCK (128). Login to comment
241 Five of these mutations resulted in disappearance from the apical surface in MDCK cells (G238V, E297G, G982R, R1153C, R1268R) (128). Login to comment

PMID: 14699511 [PubMed] Kullak-Ublick GA et al: "Enterohepatic bile salt transporters in normal physiology and liver disease."

No. Sentence Comment

117 It is caused by mutations of the BSEP (ABCB11) gene, which is located on chromosome 2q 24.173 Children with PFIC2 do not express BSEP.174 When PFIC2-related BSEP mutations are introduced artificially into rat Bsep and expressed in Madin-Darby canine kidney and Sf9 insect cells, the G238V, E297G, G982R, R1153C, and R1268Q mutations prevent the protein from trafficking to the apical membrane, whereas the G238V mutant seems to be rapidly degraded by proteasomes.175 Whereas mutation C336S affects neither Bsep transport activity nor trafficking, mutations E297G, G982R, R1153C, and R1268Q abolish taurocholate transport activity. Login to comment

PMID: 18395098 [PubMed] Strautnieks SS et al: "Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families."

No. Sentence Comment

77 The common mutations E297G, D482G, R575X, R1153C, and R1153H abolish HphI, FokI, FokI, BsrBI, and BsrBI sites, respectively, while G982R creates an AlwNI site. Login to comment
150 Missense Mutations in ABCB11 Nucleotide change Predicted effect Exon CpG site Location Change in: Size Charge Hyd/Pol Shape c.149Tb0e;C p.Leu50Ser 4 No NH2 term Y Y Y c.470Ab0e;G p.Tyr157Cys 6 No TM2 Y Y Y c.725Cb0e;T p.Thr242Ile 8 No TM4 Y Y c.890Ab0e;G p.Glu297Gly 9 No IC2 Y Y Y c.908Gb0e;A p.Arg303Lys 9 No IC2 c.937Cb0e;A p.Arg313Ser 10 Yes IC2 Y Y Y Y c.980Gb0e;A p.Gly327Glu 10 No TM5 Y Y Y c.1168Gb0e;C p.Ala390Pro 11 No TM/NBF Y c.1229Gb0e;A p.Gly410Asp 12 No TM/NBF Y Y c.1238Tb0e;G p.Leu413Trp 12 No TM/NBF c.1388Cb0e;T p.Thr463Ile 13 No Adj Walker A Y Y Y c.1396Cb0e;A p.Gln466Lys 13 No Adj Walker A Y c.1409Gb0e;A p.Arg470Gln 13 Yes Adj Walker A Y c.1415Ab0e;G p.Tyr472Cys 13 No Adj Walker A Y Y Y c.1442Tb0e;A p.Val481Glu 14 No NBF1 Y Y Y c.1445Ab0e;G p.Asp482Gly 14 No NBF1 Y Y c.1460Gb0e;C p.Arg487Pro 14 Yes NBF1 Y Y Y Y c.1468Ab0e;G p.Asn490Asp 14 No NBF1 Y c.1535Tb0e;C p.Ile512Thr 14 No NBF1 Y Y Y c.1544Ab0e;C p.Asn515Thr 14 No NBF1 Y Y c.1550Gb0e;A p.Arg517His 14 Yes NBF1 Y Y c.1621Ab0e;C p.Ile541Leu 14 No NBF1 c.1622Tb0e;C p.Ile541Thr 14 No NBF1 Y Y Y c.1643Tb0e;A p.Phe548Tyr 15 No Adj ABC c.1685Gb0e;A p.Gly562Asp 15 No ABC Y Y c.1708Gb0e;A p.Ala570Thr 15 Yes ABC/Walker B Y c.1763Cb0e;T p.Ala588Val 15 No Adj Walker B Y c.2272Gb0e;C p.Gly758Arg 19 No NBF/TM Y Y Y c.2296Gb0e;A p.Gly766Arg 19 Yes TM7 Y Y Y c.2494Cb0e;T p.Arg832Cys 21 Yes IC3 Y Y Y Y c.2576Cb0e;G p.Thr859Arg 21 No IC3 Y Y Y Y c.2842Cb0e;T p.Arg948Cys 23 Yes IC4 Y Y Y Y c.2935Ab0e;G p.Asn979Asp 23 No TM11 Y c.2944Gb0e;A p.Gly982Arg 23 Yes TM11 Y Y Y c.3086Cb0e;A p.Thr1029Lys 24 No TM12 Y Y Y Y c.3329Cb0e;A p.Ala1110Glu 25 Yes Adj Walker A Y Y Y c.3382Cb0e;T p.Arg1128Cys 25 Yes Adj Walker A Y Y Y Y c.3457Cb0e;T p.Arg1153Cys 26 Yes NBF2 Y Y Y Y c.3458Gb0e;A p.Arg1153His 26 Yes NBF2 Y Y c.3460Tb0e;C p.Ser1154Pro 26 No NBF2 Y c.3628Ab0e;C p.Thr1210Pro 27 No Adj ABC Y c.3691Cb0e;T p.Arg1231Trp 27 Yes ABC/Walker B Y Y c.3692Gb0e;A p.Arg1231Gln 27 Yes ABC/Walker B Y c.3724Cb0e;A p.Leu1242Ile 27 No Walker B c.3892Gb0e;A p.Gly1298Arg 28 No NBF2 Y Y Y NOTE. Login to comment
207 Ten mutations occurred in multiple families: R470Q, R832C,33 R948C, A1110E, and R1231Q53 have now been reported in 2 families; R1090X2 in 3 families; G982R,1,2 R1153C,1,47 and R1153H in 4 families; and R575X in 6 families.1,2,32,45 Six common missense and nonsense changes occurred at non-CpG sites: R520X and A588V33 in 2 European families and E1302X and I541L33,54 in 3 European families each. Login to comment

PMID: 22795478 [PubMed] Kubitz R et al: "The bile salt export pump (BSEP) in health and disease."

No. Sentence Comment

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. Login to comment

PMID: 23685087 [PubMed] Soroka CJ et al: "Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations."

No. Sentence Comment

136 When seven PFIC2 missense mutations were expressed in MDCK cells, five of these common mutations (G238V, E297G, G982R, R1153C and R1268Q) were unable to traffic to the apical membrane (Wang et al., 2002). Login to comment
185 In vitro studies using rat Bsep mutants of the human mutations G238V, D482G, G982R, R1153C, and R1268Q all resulted in retention of Bsep in the ER to different extents (Wang et al., 2008). Login to comment

PMID: 25027376 [PubMed] Kubitz R et al: "Genetic variations of bile salt transporters."

No. Sentence Comment

112 The missense mutations p.G238V, p.E297G, p.G982R, p.R1153C and p.R1268Q all led to a reduced expression at the apical membrane, when expressed in MDCK cells [124]. Login to comment

PMID: 25085279 [PubMed] Davit-Spraul A et al: "Liver transcript analysis reveals aberrant splicing due to silent and intronic variations in the ABCB11 gene."

No. Sentence Comment

41 Briefly, patient 1 is compound heterozygous for the missense mutation p.Arg1153Cys and the intronic substitution c.3213+4ANG. Login to comment
71 Maternal allele Paternal allele Patient 1 c.3213+4ANG p.Val444Ala&#b0; p.Arg1153Cys p.Val444Ala&#b0; Patient 2 p.Gly982Arg p.Val444Ala&#b0; p.Phe90Phe&#b0; c.3003ANG (silent p.Arg1001) Patient 3 p.Gly1003Glu p.Val444Ala&#b0; p.Ala1028Ala** p.Tyr1041X p.Val444Ala&#b0; Patient 4 p.Tyr354X p.Gly319Gly* p.Met677Val&#b0; p.Ala1028Ala** c.389+8GNA p.Gly982Arg Patient 5 p.Arg1128Cys* p.Val444Ala&#b0; p.Met677Val&#b0; p.Thr1086Thr p.Arg1128Cys p.Val444Ala&#b0; p.Met677Val&#b0; p.Thr1086Thr In bold: disease-causing mutation. In italic: common variation. Login to comment

PMID: 26382629 [PubMed] Li L et al: "Hypothyroidism Associated with ATP8B1 Deficiency."

No. Sentence Comment

71 ABCB11 mutations and immunostaining in patients with ABCB11 mutations Patient ID Sex Nucleotide change Amino acid change Mutation origin BSEP expression GGT expression 244 Female c.145C>T/- p.Q49X/- Paternal/- Absent Normal 653 Female c.1197+1G>T/c.1197+1G>T -/- Paternal/maternal Not assessed Not assessed 727 Male c.2782C>T/c.3593A>G p.R928X/p.H1198R Maternal/paternal Not assessed Not assessed 889 Female c.3457C>T/c.3623A>G p.R1153C/p.Y1208C Paternal/maternal Absent Normal 919 Female c.1493T>C/c.1493T>C p.I498T/p.I498T Paternal/maternal Not assessed Not assessed 996 Male c.612-2_4 CTA>TT/- -/- Maternal/- Absent Normal 1022 Male c.212T>A/c.677C>T p.L71H/p.S226L Paternal/maternal Absent Normal 1131 Male c.409G>A/c.2216delC p.E137K/p.P740QfsX6 De novo/paternal Absent Normal 1134 Male c.1760C>G/c.3677G>C p.S587X/p.R1226P Maternal/paternal Absent Absent 1139 Female c.2935A>G/c.3746T>G p.N979D/p.L1249X Not assessed Not assessed Not assessed 1140 Male c.542G>T/c.1370_1372dupGTG p.R181I/p.V458dup Maternal/paternal Not assessed Not assessed 1219 Female c.872T>C/c.3691C>T p.V291A/p.R1231W Maternal/paternal Not assessed Not assessed 334* Female c.2944G>A/- p.G982R/- Not assessed Normal Normal 802* Female c.3458G>A/- p.R1153H/- Not assessed Not assessed Not assessed 862* Male c.634G>A/c.849A>C/c.1638G>T p.A212T/p.E283D/p.Q546H Maternal/maternal/de novo Not assessed Not assessed 864* Male c.1727A>G/- p.N576S/- Paternal/- Normal Normal 1165* Male c.1583T>C/c.1583T>C p.I528T/p.I528T Not assessed Not assessed Not assessed 1167* Male c.334A>G/c.3233T>C p.I112V/p.I1078T Not assessed Not assessed Not assessed 1242* Male c.2783G>A/- p.R928Q/- Not assessed Not assessed Not assessed Bold: Novel mutation. Login to comment