ABCB11 p.Arg223Cys
| Reviews: |
p.Arg223Cys
D
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| Predicted by SNAP2: | A: N (53%), C: N (53%), D: D (75%), E: D (63%), F: N (53%), G: N (57%), H: N (61%), I: D (53%), K: N (53%), L: N (61%), M: N (53%), N: D (53%), P: D (71%), Q: N (61%), S: N (61%), T: N (72%), V: N (53%), W: D (63%), Y: N (61%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, S: N, T: N, V: N, W: N, Y: N, |
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[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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No. Sentence Comment
12 Three novel nonsynonymous variations, 361CÀA (Gln121Lys), 667CÀT (Arg223Cys), and 1460GÀT (Arg487Leu), were found as heterozygotes and at 0.004 allele frequencies.
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ABCB11 p.Arg223Cys 19571440:12:76
status: NEW33 Of the 6 nonsynonymous variations, 3 were novel: 361CÀA (Gln121Lys), 667CÀT (Arg223Cys), and 1460GÀT (Arg487Leu).
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ABCB11 p.Arg223Cys 19571440:33:87
status: NEW35 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.
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ABCB11 p.Arg223Cys 19571440:35:61
status: NEWX
ABCB11 p.Arg223Cys 19571440:35:393
status: NEW38 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.
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ABCB11 p.Arg223Cys 19571440:38:211
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.Arg223Cys 19571440:48:1428
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.Arg223Cys 22795478:185:919
status: NEW