ABCB11 p.Arg299Lys
| Reviews: |
p.Arg299Lys
N
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| Predicted by SNAP2: | A: D (59%), C: D (75%), D: D (71%), E: D (66%), F: D (53%), G: D (66%), H: N (72%), I: D (59%), K: N (93%), L: D (59%), M: D (59%), N: D (53%), P: D (91%), Q: N (57%), S: N (53%), T: N (57%), V: D (59%), W: D (91%), Y: D (75%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, S: N, T: D, V: D, W: D, Y: D, |
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[hide] Genetic variability, haplotype structures, and eth... Drug Metab Dispos. 2006 Sep;34(9):1582-99. Epub 2006 Jun 8. Lang T, Haberl M, Jung D, Drescher A, Schlagenhaufer R, Keil A, Mornhinweg E, Stieger B, Kullak-Ublick GA, Kerb R
Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11).
Drug Metab Dispos. 2006 Sep;34(9):1582-99. Epub 2006 Jun 8., [PMID:16763017]
Abstract [show]
Biliary excretion of bile salts and other bile constituents from hepatocytes is mediated by the apical (canalicular) transporters P-glycoprotein 3 (MDR3, ABCB4) and the bile salt export pump (ABCB11). Mutations in ABCB4 and ABCB11 contribute to cholestatic diseases [e.g., progressive familial intrahepatic cholestasis 2 (PFIC2), PFIC3, and intrahepatic cholestasis of pregnancy], and our objective was to establish genetic variability and haplotype structures of ABCB4 and ABCB11 in healthy populations of different ethnic backgrounds. All coding exons, 5 of 6 noncoding exons, 50 to 300 base pairs of the flanking intronic regions, and 2.5 to 2.8 kilobase pairs of the promoter regions of ABCB4 and ABCB11 were sequenced in 159 and 196 DNA samples of Caucasian, African-American, Japanese, and Korean origin. In total, 76 and 86 polymorphisms were identified in ABCB4 and ABCB11, respectively; among them, 14 and 28 exonic polymorphisms, and 8 and 10 protein-altering variants, of which 4 were predicted to have functional consequences. Both genes showed substantial ethnic differences with respect to allele number, frequency of common and population-specific sites, and patterns of linkage disequilibrium. Population genetic analysis suggested some selective pressure against changes in the protein, supporting the important endogenous role of these transporters. Haplotype variability was greater in ABCB11 than in ABCB4. An ABCB11 promoter haplotype was associated with significant decrease of activity compared with wild type. Our results contribute to a better understanding of the molecular basis and of ethnic differences in drug response, and provide a valuable tool for future research on the heredity of cholestatic liver injury.
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67 The numbers 1 to 53 in the variant ID column indicate all variants included in haplotype analysis and linkage disequilibrium estimation. Variant ID 5Ј Sequence Genetic Variation 3Ј Sequence Region Amino Acid Change CA AA JA Total n % n % n % n % 54 GTAGTCACA g.-15595CϾT TTTCAGAGC Promoter 186 0.5 92 0.0 88 0.0 366 0.3 1 ACACTCTCT g.-15281_-15278 delCTCT CACACAGCA Promoter 186 10.2 92 4.3 86 26.7 364 12.6 2 CCCCCTCCC g.-15150TϾC GCCCCCAGA Promoter 148 48.0 76 39.5 92 25.0 316 58.9 3 TGACTGTAG g.-15018GϾA GACCACAAC Promoter 158 10.1 78 0.0 92 29.3 328 13.1 4 ATTAAGCAC g.-14944GϾA ATCAACTCA Promoter 198 10.1 72 0.0 96 28.1 366 12.8 5 CTATTGGGA g.-14589AϾT TCTTTTCCC Promoter 198 0.0 90 2.2 88 0.0 376 0.5 55 TGAAGCAAA g.-14524AϾT TTTTTTTCC Promoter 198 0.0 90 1.1 88 0.0 376 0.3 6 TACATTTGC g.-14473GϾA TCAACTCAG Promoter 198 2.5 90 18.9 88 0.0 376 8.8 7 TTGCATAGA g.-14437GϾA GAAACATCT Promoter 198 29.8 94 22.3 96 14.6 388 24.2 8 ATTATATGT g.-14353TϾC ATAATTTTG Promoter 190 61.6 80 92.5 88 75.0 358 71.8 56 ATAAACCAT g.-14316CϾA TTATACATA Promoter 192 0.5 80 0.0 88 0.0 360 0.3 9 ACCATCTTA g.-14312TϾC ACATAAATT Promoter 192 0.0 80 0.0 88 3.4 360 0.8 57 ATAAATTCC g.-14300AϾT ATAGAGAAA Promoter 192 0.0 80 1.3 88 0.0 360 0.3 10 TTTAATTTC g.-14207TϾC GCAAATTAA Promoter 190 2.1 80 17.5 88 10.2 358 7.5 11 TTGTTACAC g.-14104CϾT TTAGGAGGA Promoter 196 2.6 92 0.0 96 0.0 384 1.3 12 CATGATAGC g.-14035AϾG CCCAACTCC Promoter 194 1.5 92 1.1 96 0.0 382 1.0 58 AAGGCTGGA g.-13910GϾA TGAGAGGCA Promoter 202 0.0 94 1.1 96 0.0 392 0.3 13 AGAGGAAGA g.-13814GϾA GCAGCACAA Promoter 194 0.0 94 6.4 88 0.0 376 1.6 14 GCACAAATA g.-13801TϾC ATTGGAGCT Promoter 194 1.5 94 0.0 88 0.0 376 0.8 15 CTCAGACTT g.-13662TϾC TGAGCAAGG Promoter 192 0.0 94 7.4 86 0.0 372 1.9 83 TTAAAGGTA g.-13523͓T͔9 GTCTTGTTA Promoter 200 10.0 90 11.1 96 28.1 386 14.8 84 TTAAAGGTA g.-13523͓T͔10 GTCTTGTTA Promoter 200 9.0 90 18.9 96 6.3 386 10.6 85 TTAAAGGTA g.-13523͓T͔11 GTCTTGTTA Promoter 200 65.0 90 53.3 96 45.8 386 57.5 86 TTAAAGGTA g.-13523͓T͔12 GTCTTGTTA Promoter 200 16.0 90 16.7 96 19.8 386 17.1 59 CTGGGCCAG g.-13595GϾA AGCATCTGG Promoter 198 0.0 94 1.1 96 0.0 388 0.3 16 CAAGCACAC g.-13333TϾC CTGTGTTTG Promoter 196 0.0 76 0.0 96 3.9 368 0.9 17 ATGTTTCTC g.-13297GϾA TATGTCACT Promoter 196 0.0 76 3.9 96 0.0 368 0.8 60 TCCACAGTG g.-13142GϾA AGTCCATTA Exon 1 194 0.0 76 0.0 92 1.1 362 0.3 18 TTGATTAAA g.-77GϾA AAGAAAGAA Intron 1 202 2.5 88 11.4 90 12.2 380 6.8 19 ATTTTTTTT g.1319delT CTGACAGAT Intron 2 198 0.0 88 3.4 92 0.0 378 0.8 20 TTTAAATCC g.3754TϾC TATGTTTTT Intron 3 198 7.1 62 32.3 88 12.5 348 12.9 21 GTTACAAGA g.3781TϾC GAGAAGAAA Exon 4 D36D 198 0.0 62 0.0 88 26.1 348 6.6 22 GAATCTAGT g.4542AϾT ACTAAATTA Intron 4 184 0.0 90 0.0 92 2.2 366 0.5 61 CAAGTTTCG g.4621GϾA TTTTCTTCA Exon 5 R52R 184 0.0 90 1.1 92 0.0 366 0.3 23 AGATGTTTT g.4735TϾC ATTGACTAC Exon 5 F90F 184 2.7 90 13.3 92 12.0 366 7.7 24 GGGTAGGTT g.4862GϾA TTTTTGTTT Intron 5 182 4.9 90 2.2 94 0.0 366 3.0 25 GCTGAACAT g.21416CϾT GAGAGCGAA Exon 6 I134I 192 0.0 86 18.6 88 0.0 366 4.4 26 AGCTCCTCC g.21507GϾA TATAATTTA Intron 6 196 0.0 92 18.5 92 0.0 380 4.5 27 ACAATGAGA g.21554TϾG GCAATGTGT Intron 6 196 0.0 92 0.0 92 4.3 380 1.1 62 TGTATTGAA g.22567AϾT GTACTTTCT Intron 6 198 0.5 94 0.0 94 0.0 386 0.3 63 TTTGAATGA g.24203TϾC CAAATTCAG Intron 7 192 0.5 90 0.0 94 0.0 376 0.3 64 TCTAGTGAT g.24248AϾG TTAATAAAA Exon 8 I206V 194 0.0 90 1.1 96 0.0 380 0.3 28 TACGGACTA g.27224TϾC GAGCTGAAG Exon 9 Y269Y 200 0.0 80 0.0 96 27.1 376 6.9 65 CTGATGAAG g.27268TϾC CATTTCATC Exon 9 V284A 200 0.5 80 0.0 96 0.0 376 0.3 66 GTGAGAAAA g.27313GϾA AGAGGTTGA Exon 9 R299K 200 0.0 80 0.0 96 1.0 376 0.3 29 ACTGCATCA g.31773CϾT GGCCTGTTT Intron 9 178 5.1 70 1.4 48 0.0 296 3.4 30 TGTTTCTGC g.31811CϾT GAAATTGAC Intron 9 196 4.6 72 4.2 86 0.0 354 3.4 31 TTGACTCAA g.31825GϾA CATTTTGTC Intron 9 196 4.6 72 26.4 86 0.0 354 7.9 32 GACTCAAGC g.31827AϾG TTTTGTCTT Intron 9 196 70.4 72 84.7 86 90.7 354 78.2 33 TAGAAAAGG g.31890AϾG ATAGTGATG Exon 10 G319G 196 4.6 72 26.4 86 0.0 354 7.9 34 GACTTATTG g.32034AϾT CCGAGACAT Intron 10 196 0.0 66 4.5 82 0.0 344 0.9 67 CCTCAGTGT g.38161CϾT ATAGTAGGA Exon 11 V366V 196 0.0 88 1.1 94 0.0 378 0.3 35 CATTTTTGA g.38248GϾA ACAATAGAC Exon 11 E395E 196 0.0 88 8.0 96 0.0 380 1.8 36 GCAGAGATA g.41348CϾT GCCAAAGAT Intron 11 198 0.0 72 2.8 80 0.0 350 0.6 37 CCACAAATT g.41622GϾT CTCATTTTC Intron 12 196 1.0 72 0.0 74 0.0 342 0.6 38 CAGTGACAA g.44255delT CTGAACTTT Intron 12 190 0.0 94 2.1 92 0.0 376 0.5 39 TCAACATGG g.44308TϾC CATTAAACC Exon 13 V444A 190 59.5 90 65.6 92 80.4 372 66.1 40 TTGATCAAA g.44481CϾT AGAAAGGTG Intron 13 188 59.0 90 65.6 92 80.4 370 65.9 68 CAAGGAGGC g.46246CϾT AATGCCTAC Exon 14 A535A 184 0.0 86 0.0 96 1.0 366 0.3 41 GGGAGAAAC g.46311TϾC AAGAGGTCG Intron 14 182 60.4 86 66.3 94 79.8 362 66.9 42 GTTGCTCAT g.48611CϾG GCTTGTCTA Exon 16 R616G 194 0.0 90 2.2 96 0.0 380 0.5 69 CGCTTGTCT g.48620AϾG CGGTCAGAG Exon 16 T619A 194 0.0 90 1.1 96 0.0 380 0.3 70 CAGAGCTGC g.48634AϾG GATACCATC Exon 16 A623A 194 0.0 90 1.1 96 0.0 380 0.3 43 GAAGATGAC g.49653AϾG TGCTTGCGA Exon 17 M677V 190 4.2 86 14.0 88 0.0 364 5.5 71 CCGGCAAC g.53835GϾA CTCCAAGTC Exon 18 R698H 196 0.5 82 0.0 94 0.0 372 0.3 72 GAACCTCCA g.53876TϾC TAGCTGTTG Exon 18 L712L 196 0.5 82 0.0 94 0.0 372 0.3 44 TTAATATAA g.59981CϾA CCTCTCTCT Intron 18 192 43.2 84 21.4 90 27.8 366 34.4 45 AATAGATTT g.73116_73119delATTT TTCTATTTA Intron 19 192 0.0 66 6.1 96 0.0 354 1.1 46 ATTTATAAT g.73132_73133insCAA AAAGTTACT Intron 19 194 0.0 66 6.1 96 0.0 356 1.1 47 ACTTTCTTG g.73148TϾC TTACTATCT Intron 19 196 69.4 66 93.9 96 0.0 358 82.1 qanal/courses/predoc97/blosum62.cmp), and Grantham values (Grantham, 1974).
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ABCB11 p.Arg299Lys 16763017:67:3895
status: NEW117 Six singletons were detected in exon 8 (c.616AϾG 3 p.I206V), exon 9 (c.851TϾC 3 p.V284 and c.A896GϾA 3 p.R299K), exon 16 (1855AϾG 3 p.T619A), exon 18 (c.2093GϾA 3 p.R698H), and exon 23 (c.2873GϾA 3 p.R958Q).
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ABCB11 p.Arg299Lys 16763017:117:123
status: NEW177 Amino Acid Change Scoring Systems for Nonsynonymous Variants Grantham SIFT PolyPhen Blosum62 EC/EU MDR3 D87E 45 1.00 0.48 2 EC P95S 74 0.48 0.87 -1 EC T175A 58 0.01 0.72 -1 EC I367V 29 0.23 0.96 3 EC E450G 98 0.01 0.13 -2 EC R590Q 43 0.01 2.51 1 EC R652G 125 0.36 1.47 -2 EU E1099G 98 0.04 1.58 -2 EC BSEP I206V 29 1.00 0.23 3 EU V284A 64 0.13 0.43 -2 EC R299K 26 1.00 0.38 2 EU V444A 64 0.63 0.78 -2 EC R616G 125 0.01 3.16 -2 EC T619A 58 0.00 1.78 -1 EC M677V 21 0.29 0.82 1 EU R698H 29 0.30 0.57 0 EC A865V 64 0.02 1.12 0 EC R958Q 43 0.04 0.24 1 EU neutral mutation model (Tajima, 1989).
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ABCB11 p.Arg299Lys 16763017:177:355
status: NEW[hide] Prediction of drug-induced intrahepatic cholestasi... Expert Opin Drug Saf. 2007 Jan;6(1):71-86. Sakurai A, Kurata A, Onishi Y, Hirano H, Ishikawa T
Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump.
Expert Opin Drug Saf. 2007 Jan;6(1):71-86., [PMID:17181454]
Abstract [show]
Drug-induced intrahepatic cholestasis is one of the major causes of hepatotoxicity, which often occur during the drug discovery and development process. Human ATP-binding cassette transporter ABCB11 (sister of P-glycoprotein/bile salt export pump) mediates the elimination of cytotoxic bile salts from liver cells to bile, and, therefore, plays a critical role in the generation of bile flow. The authors have recently developed in vitro high-speed screening and quantitative structure-activity relationship analysis methods to investigate the interaction of ABCB11 with a variety of compounds. Based on the extent of inhibition of the bile salt export pump, the authors analysed the quantitative structure-activity relationship to identify chemical groups closely associated with the inhibition of ABCB11. This approach provides a new tool to predict compounds with a potential risk of drug-induced intrahepatic cholestasis.
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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.Arg299Lys 17181454:120:227
status: NEW121 Nonsynonymous polymorphisms and mutations in the ABCB11 gene NCBI No. Exon Nucleotide Amino acid alteration Phenotype Ref. Position Alteration rs11568361 5 167 C→T Ser56Leu - [102] - 5 341 G→C Ser114Arg PFIC2 [47]* - 6 557 A→G Glu186Gly BRIC2 [45,48] - 6 580 T→C Ser194Pro - [44] rs11568358 7 616 A→G Ile206Val - [102] - 7 695 T→del Frame shift at position 232 PFIC2 [47] - 7 713 G→T Gly238Val PFIC2 [47] - 8 779 G→A Gly260Asp - [44] - 8 851 T→C Val284Ala - [44] rs11568372 8 890 A→G Glu297Gly PFIC2/BRIC2 [35,43,45,47,102] rs2287617 8 896 G→A Arg299Lys - [102] - 8 908 G→del Frame shift at position 303 PFIC2 [35] - 9 1007 G→C Cys336Ser PFIC2 [47] - 9 1015 C→G Leu339Val - [46] - 11 1244 G→A Arg415Gln - [39] - 11 1294 G→C Arg432Thr BRIC2 [43] rs2287622 12 1331 T→C Val444Ala ICP/PFIC2?
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ABCB11 p.Arg299Lys 17181454:121:621
status: NEW[hide] Genetic variations of the ABC transporter gene ABC... Drug Metab Pharmacokinet. 2009;24(3):277-81. Kim SR, Saito Y, Itoda M, Maekawa K, Kawamoto M, Kamatani N, Ozawa S, Sawada J
Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population.
Drug Metab Pharmacokinet. 2009;24(3):277-81., [PMID:19571440]
Abstract [show]
The bile salt export pump (BSEP) encoded by ABCB11 is located in the canalicular membrane of hepatocytes and mediates the secretion of numerous conjugated bile salts into the bile canaliculus. In this study, 28 ABCB11 exons (including non-coding exon 1) and their flanking introns were comprehensively screened for genetic variations in 120 Japanese subjects. Fifty-nine genetic variations, including 19 novel ones, were found: 14 in the coding exons (6 nonsynonymous and 8 synonymous variations), 4 in the 3'-UTR, and 41 in the introns. Three novel nonsynonymous variations, 361C>A (Gln121Lys), 667C>T (Arg223Cys), and 1460G>T (Arg487Leu), were found as heterozygotes and at 0.004 allele frequencies. These data provide fundamental and useful information for genotyping ABCB11 in the Japanese and probably other Asian populations.
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41 The three known nonsynonymous variations, 896GÀA (Arg299Lys), 1331CÀT (Ala444Val), and 2594CÀT (Ala865Val), were detected at 0.004, 0.267, and 0.004 frequencies, respectively, which are similar to the previously reported Japanese data.7) One variation, 1331CÀT (Ala444Val), was found 14 residues upstream of the Walker A motif in the NBF1 domain in the large cytoplasmic loop between TMD6 and TMD7.
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ABCB11 p.Arg299Lys 19571440:41:55
status: NEW48 Summary of ABCB11 variations detected in this study SNP ID Reference Location Position Nucleotide change Amino acid change Frequency This Study dbSNP (NCBI) NT_005403.16 From the translational initiation site or from the end of the nearest exonb MPJ6_AB11001 rs4148772 7, 8 Intron 1 20084130 IVS1－50 ACTTTGATTAAAG/AAAGAAAGAAGAG 0.058 MPJ6_AB11002 rs10199694 Intron 3 20082623 IVS3＋83 AAGCAGAGAATAC/TTTTCATGCACAT 0.058 MPJ6_AB11003 rs4148775 8 Intron 3 20080475 IVS3－193 TGAGATTGAGCTA/GTACTGAAATCTC 0.225 MPJ6_AB11004 rs4148776 7, 8 Intron 3 20080300 IVS3－18 GTCTTTAAATCCT/CTATGTTTTTCTC 0.058 MPJ6_AB11005 rs3815675 7, 8 Exon 4 20080273 108 CAGGTTACAAGAT/CGAGAAGAAAGGT Asp36Asp 0.225 MPJ6_AB11006a Intron 4 20079560 IVS4－122 CACTCAATTAAGG/ATGATTCCCATGA 0.029 MPJ6_AB11007 7 Intron 4 20079512 IVS4－74 TGAGAATCTAGTA/TACTAAATTAAGT 0.021 MPJ6_AB11008 rs4148777 7, 8 Exon 5 20079319 270 GACAGATGTTTTT/CATTGACTACGAC Phe90Phe 0.058 MPJ6_AB11009a Exon 5 20079310 279 TTTTATTGACTC/TGACGTTGAGTTA Tyr93Tyr 0.004 MPJ6_AB11010a Exon 5 20079228 361 AGTTCCCTCAACC/AAGAACATGACAA Gln121Lys 0.004 MPJ6_AB11011a Intron 5 20062886 IVS5－236 ATATGCATATTTT/CCTGTGATTGGTA 0.004 MPJ6_AB11012 7 Intron 6 20062500 IVS6＋63 ACTACAATGAGAT/GGCAATGTGTTGC 0.017 MPJ6_AB11013a Intron 7 20059917 IVS7－107 ATCCAAGGGTGAT/CAGGGATAGAGAG 0.004 MPJ6_AB11014a Exon 8 20059755 667 CTTTTCATTCAGC/TGCATGACCTCGA Arg223Cys 0.004 MPJ6_AB11015 rs2287614 8 Intron 8 20056962 IVS8－109 GTTACAGTGAGAA/CTCTAATATTGTA 0.058 MPJ6_AB11016 rs2287615 8 Intron 8 20056940 IVS8－87 GTATTAAACCCAT/AGCCACATGTTAA 0.267 MPJ6_AB11017 rs2287616 7, 8 Exon 9 20056830 807 GTTTACGGACTAT/CGAGCTGAAGGCC Tyr269Tyr 0.267 MPJ6_AB11018 rs2287617 7 Exon 9 20056741 896 GTGGTGAGAAAAG/AAGAGGTTGAAAG Arg299Lys 0.004 MPJ6_AB11019 rs4148780 8 Intron 9 20056621 IVS9＋108 TCTGTGGCCTCCA/GGAGGAAGTACTT 0.058 MPJ6_AB11020 rs2287618 7 Intron 9 20052227 IVS9－15 ATTGACTCAAGCG/ATTTTGTCTTCAC 0.217 MPJ6_AB11021a Intron 11 20045737 IVS11＋57 GGGGGTGGGGCAC/AAGAATGAACTCC 0.004 MPJ6_AB11022a Intron 11 20045731 IVS11＋63 GGGGCACAGAATG/AAACTCCTGAAGA 0.004 MPJ6_AB11023a Intron 11 20042655 IVS11－40 TTGTGCATCTTAG/CTTTGAGTTTACA 0.004 MPJ6_AB11024a Exon 12 20042565 1248 GTTGGATCGAATC/AAAGGGTGAAATT Ile416Ile 0.008 MPJ6_AB11025 rs4148783 8 Intron 12 20042389 IVS12＋116 GTAATAGGGAATG/AGAGGTGTCTTTC 0.250 MPJ6_AB11026a Intron 12 20042383 IVS12＋122 GGGAATGGAGGTG/ATCTTTCTCTGAA 0.062 MPJ6_AB11027 rs55669065 Intron 12 20039861 IVS12－93 CACACAGACACCG/AAGTATCAACACA 0.012 MPJ6_AB11028 rs2287622 7, 8 Exon 13 20039746 1331 ACCTCAACATGGC/TCATTAAACCAGG Ala444Val 0.267 MPJ6_AB11029 rs2287623 7, 8 Intron 13 20039573 IVS13＋70 ATATTGATCAAAT/CAGAAAGGTGTAG 0.237 MPJ6_AB11030 rs2389605 Intron 13 20039469 IVS13＋174 TAACAGTGTTCAA/GTGAATAACCAGT 0.237 MPJ6_AB11031 rs4148786 8 Intron 13 20038064_ 20038065 IVS13－87_－86 CTCTATTTTTTC-/CTGCCCATTGGTC 0.004 MPJ6_AB11032a Exon 14 20037953 1460 GCCATGACATTCG/TCTCTCTTAACAT Arg487Leu 0.004 MPJ6_AB11033a Exon 14 20037907 1506 TGGGATAGTGGAG/ACAAGAGCCAGTT Glu502Glu 0.004 MPJ6_AB11034 7 Exon 14 20037808 1605 TGCCAAGGAGGCC/TAATGCCTACAAC Ala535Ala 0.008 MPJ6_AB11035 rs2241340 7, 8 Intron 14 20037743 IVS14＋32 CCTGGGAGAAACC/TAAGAGGTCATAG 0.237 MPJ6_AB11036 rs2241341 8 Intron 14 20037695 IVS14＋80 TACACATTTCTTT/CTCGTATGATTCC 0.237 MPJ6_AB11037 rs55868238 Intron 14 20037647 IVS14＋128 TGTTTTAGTTTCA/-TGCCTGAAAAAG 0.062 MPJ6_AB11038 rs2193831 8 Intron 14 20036295 IVS14－152 AGACAATAACCCA/GTCTGGGGAAGGG 0.237 MPJ6_AB11039 rs2389612 8 Intron 15 20035603 IVS15－124 AATGTCTGCACAG/ACCTATTTAAGAA 0.237 MPJ6_AB11040 rs4148795 8 Intron 18 20030037 IVS18＋97 TTTTCTAGGTATA/GTATCTAGCAGTG 0.417 MPJ6_AB11041 rs4148796 8 Intron 18 20030036 IVS18＋98 TTTCTAGGTATAT/CATCTAGCAGTGT 0.417 MPJ6_AB11042 rs853772 7, 8 Intron 18 20024073 IVS18－17 TGATTAATATAAA/CCCTCTCTCTGCT 0.412 MPJ6_AB11043 rs853773 8 Intron 19 20023765 IVS19＋127 ATCTCTAAAGAAC/TGAAAAATTTCCT 0.396 MPJ6_AB11044 7 Exon 21 20010549 2594 TTGCTACAGATGC/TTTCCCAAGTTCA Ala865Val 0.004 MPJ6_AB11045a Intron 21 20010502 IVS21＋31 AATAGAAGTATAT/GTAACTGCATTGG 0.004 MPJ6_AB11046 rs11568379 Intron 21 20002386 IVS21－25 TGTGTCTGAGACG/AGGTTGATTGCTT 0.054 MPJ6_AB11047a Intron 22 20002132 IVS22＋26 TCTAATTTTCCCA/GTTCCTCATGGCT 0.004 MPJ6_AB11048a Intron 22 20002091 IVS22＋67 AACTGTTAAAAAC/TGAGTAGTACGAA 0.004 MPJ6_AB11049 rs497692 7, 8 Exon 24 19998434 3084 TGTACTGAGTGCG/AACAGCTCTTGGA Ala1028Ala 0.442 MPJ6_AB11050 7 Intron 24 19998280 IVS24＋25 ATACTATGCAGCC/AATAAAAAAGGAT 0.004 MPJ6_AB11051a Intron 25 19996478 IVS25＋115 CTTGCCTAAGGCA/CCTTACCCCATGC 0.042 MPJ6_AB11052 rs7561903 Intron 26 19992983 IVS26＋101 CTGAAAATCCCAA/CATCCAAAATGTT 0.104 MPJ6_AB11053a Intron 26 19992965 IVS26＋119 AAATGTTCCAAAA/GTTCAAAAATTTT 0.004 MPJ6_AB11054a Intron 27 19989910 IVS27－160 CACTGATGCATTG/ACATTCAGGGAAT 0.004 MPJ6_AB11055 rs579275 7, 8 Intron 27 19989784 IVS27－34 GAGCAATCATGCG/ATCTTTGCATCAA 0.437 MPJ6_AB11056 rs473351 8, 15 3?-UTR 19989314 4202 (*236)c ACTAGGGTCCATG/ATGAGGGAAAACC 0.054 MPJ6_AB11057 rs3732038 3?-UTR 19989269 4247 (*281)c GCCACCACTCAGT/GGCTTCTCTGTGC 0.004 MPJ6_AB11058 rs495714 8 3?-UTR 19989182 4334 (*368)c AACTCCTCAAGGA/GCAGAGAACTGTC 0.437 MPJ6_AB11059 rs496550 8 3?-UTR 19989130 4386 (*420)c AGAGGCGGGTCTG/ATAACAGGCAATC 0.437 a Novel variations detected in this study.
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ABCB11 p.Arg299Lys 19571440:48:1794
status: NEW51 280 Su-Ryang KIM, et al. 281281Genetic Variations of ABCB11 in Japanese quency in Japanese (0.196-0.267) is slightly lower than that in Caucasians (0.405) and African-Americans (0.344) (described as g.44308TÀC [Val444Ala] in a previous paper).7) Two other known variations, 896GÀA (Arg299Lys) and 2594CÀT (Ala865Val), were detected only in the Japanese population at allele frequencies of 0.010 for 896GÀA and 0.024 for 2594CÀT, respectively.7) Both variations are located in the cytoplasmic loops between TMD4 and TMD5 and between TMD8 and TMD9.
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ABCB11 p.Arg299Lys 19571440:51:293
status: NEW[hide] The bile salt export pump (BSEP) in health and dis... Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):536-53. doi: 10.1016/j.clinre.2012.06.006. Epub 2012 Jul 12. Kubitz R, Droge C, Stindt J, Weissenberger K, Haussinger D
The bile salt export pump (BSEP) in health and disease.
Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):536-53. doi: 10.1016/j.clinre.2012.06.006. Epub 2012 Jul 12., [PMID:22795478]
Abstract [show]
The bile salt export pump (BSEP) is the major transporter for the secretion of bile acids from hepatocytes into bile in humans. Mutations of BSEP are associated with cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 2 (PFIC-2), benign recurrent intrahepatic cholestasis type 2 (BRIC-2) and genetic polymorphisms are linked to intrahepatic cholestasis of pregnancy (ICP) and drug-induced liver injury (DILI). Detailed analysis of these diseases has considerably increased our knowledge about physiology and pathophysiology of bile secretion in humans. This review focuses on expression, localization, and function, short- and long-term regulation of BSEP as well as diseases association and treatment options for BSEP-associated diseases.
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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.
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ABCB11 p.Arg299Lys 22795478:185:620
status: NEW