ABCMdb

PMID: 19571440

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., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCB11 p.Gln121Lys ABCB11 p.Arg487Leu ABCB11 p.Arg223Cys Three novel nonsynonymous variations, 361CÀA (Gln121Lys), 667CÀT (Arg223Cys), and 1460GÀT (Arg487Leu), were found as heterozygotes and at 0.004 allele frequencies. Login to comment 33 ABCB11 p.Gln121Lys ABCB11 p.Arg487Leu ABCB11 p.Arg223Cys Of the 6 nonsynonymous variations, 3 were novel: 361CÀA (Gln121Lys), 667CÀT (Arg223Cys), and 1460GÀT (Arg487Leu). Login to comment 35 ABCB11 p.Gln121Lys ABCB11 p.Arg487Leu ABCB11 p.Arg487Leu ABCB11 p.Arg223Cys ABCB11 p.Arg223Cys The nonsynonymous SNPs 361CÀA (Gln121Lys), 667CÀT (Arg223Cys), and 1460GÀT (Arg487Leu) are located in the extracellular loop between TMD1 and TMD2, TMD3 and the large cytoplasmic loop between TMD6 and TMD7, respectively.4) Using the PolyPhen program (http:/ /genetics.bwh.harvard.edu/pph/) to predict functional effects of the three amino acid substitutions, two substitutions, Arg223Cys and Arg487Leu, are expected to alter protein function based on PSIC (position-specific independent count) score differences derived from multiple alignments. Login to comment 38 ABCB11 p.Arg487His ABCB11 p.Arg487Pro ABCB11 p.Arg487Leu ABCB11 p.Arg223Cys The two substitutions at the same position, Arg487His and Arg487Pro, were found in patients with severe BSEP deficiency syndrome, PFIC2.13,14) Thus, it is possible that bile acid homeostasis in the subject with Arg223Cys or Arg487Leu may be disturbed. Login to comment 41 ABCB11 p.Ala865Val ABCB11 p.Arg299Lys 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. Login to comment 48 ABCB11 p.Ala865Val ABCB11 p.Arg299Lys ABCB11 p.Gln121Lys ABCB11 p.Arg487Leu ABCB11 p.Arg223Cys 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. Login to comment 51 ABCB11 p.Val444Ala ABCB11 p.Ala865Val ABCB11 p.Arg299Lys 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. Login to comment 52 ABCB11 p.Arg958Gln The variation 2873GÀA (Arg958Gln) previously reported in Japanese at a frequency of 0.011 was not detected in this study. Login to comment 53 ABCB11 p.Met677Val ABCB11 p.Arg698His ABCB11 p.Val284Ala ABCB11 p.Thr619Ala ABCB11 p.Arg616Gly ABCB11 p.Ile206Val Six variations previously reported in other ethnic groups were not detected: 616AÀG (Ile206Val; found with 0.011 frequency in African-Americans), 851TÀC (Val284Ala; 0.005 in Caucasians), 1846CÀG (Arg616Gly; 0.022 in African-Americans), 1855AÀG (Thr619Ala; 0.011 in African-Americans), 2029AÀG (Met677Val; 0.042 in Caucasians and 0.14 in African-Americans), and 2093GÀA (Arg698His; 0.005 in Caucasians).7) These variations might be ethnic-specific. Login to comment