PMID: 16763017

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., [PubMed]
Sentences
No. Mutations Sentence Comment
63 ABCB4 p.Arg590Gln
X
ABCB4 p.Arg590Gln 16763017:63:5390
status: NEW
view ABCB4 p.Arg590Gln details
ABCB4 p.Thr175Ala
X
ABCB4 p.Thr175Ala 16763017:63:4167
status: NEW
view ABCB4 p.Thr175Ala details
ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:63:5474
status: NEW
view ABCB4 p.Arg652Gly details
ABCB4 p.Pro95Ser
X
ABCB4 p.Pro95Ser 16763017:63:3673
status: NEW
view ABCB4 p.Pro95Ser details
ABCB4 p.Asp87Glu
X
ABCB4 p.Asp87Glu 16763017:63:3591
status: NEW
view ABCB4 p.Asp87Glu details
ABCB4 p.Ile367Val
X
ABCB4 p.Ile367Val 16763017:63:4583
status: NEW
view ABCB4 p.Ile367Val details
ABCB4 p.Glu450Gly
X
ABCB4 p.Glu450Gly 16763017:63:4822
status: NEW
view ABCB4 p.Glu450Gly details
The numbers 1 to 42 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 KO JA Total n % n % n % n % 43 TCAATGCAC g.-7676AϾT GTCTCACAA PromA 110 0.9 96 0.0 88 0.0 294 0.3 44 CTACCCTCT g.-7554TϾC CAATGCCTC PromA 110 0.9 96 0.0 88 0.0 294 0.3 45 GAGTGAAGT g.-7253GϾA TAGAAATCT PromA 106 0.0 96 1.0 94 0.0 296 0.3 46 AATTTAGAA g.-7114AϾT ACTCAATAG PromA 108 0.0 96 1.0 94 0.0 298 0.3 1 AAGAGGAAA g.-7094GϾC TTTCTTGTA PromA 108 13.0 96 30.2 94 24.5 298 22.1 47 CAAGAATTT g.-6816CϾT ATTAGGCAA PromA 102 0.0 96 1.0 92 0.0 290 0.3 48 GAGAGAGAG g.-6639AϾC GAGCTGAAT PromA 110 0.9 90 0.0 92 0.0 292 0.3 49 GAGAGAGAG g.-6637_-6636 delAG CTGAATCAG PromA 110 0.0 90 1.1 92 0.0 292 0.3 2 GTGCCTTTG g.-6588GϾT GTGTGCTGG PromA 110 2.7 88 0.0 92 2.2 290 1.7 3 AAAGAAGAA g.-6540CϾT GAAACCAAA PromA 108 14.8 86 26.7 90 27.8 284 22.5 4 TTAGTGACC g.-6325AϾG AAAGTTTGG PromA 108 17.6 90 31.1 92 26.1 290 24.5 5 ATTCTTTTT g.-6014GϾT TACAAACCC PromA 108 16.7 94 28.7 88 26.1 290 23.4 50 ACTGGTGCT g.-5941GϾA TGGGCACTA PromA 108 0.0 94 0.0 88 1.1 290 0.3 6 TGAAGTCAC g.-5859GϾA TGGCCAGAG PromA 108 16.7 94 28.7 88 26.1 290 23.4 7 ATGAGATGA g.-5717TϾC ATATATGTG PromA 110 0.0 92 1.1 86 3.5 288 1.4 8 CCTTCTTTA g.-5610TϾC ATGCCTAAA PromA 110 100.0 96 100.0 94 97.9 300 99.3 9 TAAGTGTGG g.-5570GϾC CAGCAATTA PromA 110 12.7 96 29.2 94 24.5 300 21.7 51 TACTCTCAC g.-5509GϾA GCTCTTATG PromA 110 0.0 96 1.0 94 0.0 300 0.3 10 CTCTCTTGT g.-5236CϾT TGAGTAATA PromA 108 15.7 90 27.8 94 26.6 292 22.9 52 GAGGATAAA g.-2551AϾT AAGAAAGAT PromB 126 0.0 88 0.0 90 1.1 304 0.3 11 AGCCTTACA g.-2478TϾG CAATGCATA PromB 126 4.8 88 0.0 90 2.2 304 2.6 12 GAAGGAATT g.-1921TϾC GGGTTGATT PromB/Exon -3 122 4.9 92 0.0 82 1.2 296 2.4 53 GAAGAGAAT g.-1899CϾA CTCATGGTC PromB/Exon -3 122 0.8 92 0.0 82 0.0 296 0.3 13 ATCCTAATA g.-1603AϾT CACCCTTAT PromB 128 0.0 94 2.1 86 1.2 308 1.0 14 TTTATAGAT g.-1584CϾT CAATGACTG PromB/Exon -2 118 11.0 94 29.8 74 23.0 286 20.3 54 ACACCAGGG g.-1510TϾG CCACCCAGC PromB 126 0.0 94 1.1 68 0.0 288 0.3 15 CTTATACCA g.-1484TϾC GCTCTGCTT PromB 126 0.0 94 1.1 68 5.9 288 1.7 55 TTTGAAAGT g.-1146CϾT TCCGGTTTC PromB 126 0.0 92 1.1 82 0.0 300 0.3 16 TGGTAGGAG g.-1031CϾT AGAGACAAT PromB 126 11.1 92 30.4 82 24.4 300 20.7 56 GAGACAATT g.-1020CϾG AATACAGAC PromB 126 0.0 92 1.1 82 0.0 300 0.3 17 ATTCAATAC g.-1014AϾG GACAGAAGT PromB 126 13.5 92 30.4 82 24.4 300 21.7 18 GAACTGGGG g.-682AϾC TGCGGAAGC PromB/Exon -1 124 1.6 70 0.0 64 0.0 258 0.8 19 AGGCTCCAG g.-495CϾG CTGATCTCG PromB 126 17.5 86 29.1 84 28.6 296 24.0 20 GCGCCCCGG g.-414CϾT GGCAAGAGC PromB 126 4.8 86 3.5 84 6.0 296 4.7 21 GGCAGGCTG g.-395CϾG GCCCCTGGC PromB 126 13.5 86 3.5 84 6.0 296 8.4 22 GCCCGCGCC g.-378TϾC AGCCTGGGG PromB 126 26.2 86 27.9 84 20.2 296 25.0 57 GCGTTTCCC g.-292GϾT GGCCGGACG PromB 128 0.0 96 0.0 92 1.1 316 0.3 58 CCGGACGCG g.-280CϾA GTGGGGGGC PromB 126 0.8 86 0.0 84 0.0 296 0.3 59 CCCTGCCAG g.-186AϾG CACGCGCGA PromB/Exon 1 128 0.0 96 1.0 92 0.0 316 0.3 23 TGCCCCCGG g.-75GϾT CCCCGCGAC PromB 128 0.0 96 0.0 92 1.1 316 0.3 24 TTTATGTCG g.12597CϾT TGGGTACCA Exon 4 L59L 126 12.7 96 25.0 94 21.3 316 19.0 60 CAAATTTGT g.12680TϾG GATACTGCA Exon 4 V86V 126 0.0 96 0.0 94 1.1 316 0.3 61 ATTTGTTGA g.12683TϾG ACTGCAGGA Exon 4 D87E 126 0.0 96 0.0 94 1.1 316 0.3 62 TTCTCCTTT g.12705CϾT CAGGTAAGC Exon 4 P95S 126 0.0 96 0.0 94 1.1 316 0.3 63 TAGCTTTCA g.20782TϾG ACATTTAAA Intron 4 114 0.0 88 1.1 70 0.0 272 0.4 25 TTTTAAAAA g.20813CϾT CTGGCAATG Intron 4 116 3.4 90 1.1 70 0.0 276 1.8 26 TCACCTATT g.21044AϾG TTATCATTT Intron 5 122 16.4 52 15.4 46 32.6 220 19.5 27 AAAAGAAAA g.22281_22284delGAAAA AAGAAAAGA Intron 5 126 7.9 88 0.0 84 0.0 298 3.4 28 TGACATCAA g.22490CϾT GACACCACT Exon 6 N168N 126 42.9 88 37.5 90 44.4 304 47.7 29 GAACTCAAT g.22509AϾG CGCGGCTAA Exon 6 T175A 126 3.2 88 0.0 90 0.0 304 1.3 64 CTCTGCAGC g.23831CϾT GTTTGGGCA Exon 7 A232A 128 0.0 94 0.0 90 1.1 312 0.3 65 AAGGGTTGA g.25313CϾG CAGAGTGCC Intron 7 124 0.8 96 0.0 90 0.0 310 0.3 30 TGTCCAGAT g.25376AϾT CTCTCGGCA Exon 8 I237l 126 15.1 96 27.1 90 27.8 312 22.4 66 GTTAATATA g.28354TϾC GCATCATAT Exon 9 Y309Y 128 0.8 96 0.0 92 0.0 316 0.3 67 GCATATGTG g.30584AϾG TCTTTGATA Exon 10 I367V 118 0.8 92 0.0 92 0.0 302 0.3 68 TAATATTTA g.31823TϾG AGGAATTCC Intron 11 128 0.0 96 0.0 92 1.1 316 0.3 31 ACTTTTTTT g.31941delT CAAATTTCA Intron 11 128 7.0 96 3.1 94 1.1 318 4.1 69 ACCCTGATG g.32140AϾG GGGCACAGT Exon 12 E450G 128 0.0 96 1.0 94 0.0 318 0.3 70 ACAAATTTG g.32232CϾT GTGTGAATC Intron 12 128 0.0 96 1.0 94 0.0 318 0.3 32 GGCAATGCC g.32277GϾT ATGGATAAT Intron 12 124 6.5 96 3.1 94 3.2 314 4.5 33 CAGCTATTA g.35024AϾG ATGGTTAAA Intron 12 124 95.2 94 70.2 94 72.3 312 80.8 71 ACAGGTAAA g.35273GϾA CCTCTGATA Intron 13 126 0.0 96 0.0 94 1.1 316 0.3 72 AGTGTGCCA g.43862AϾG TACTGTAAC Intron 14 122 0.8 88 0.0 72 0.0 282 0.4 34 TGTGCCAAT g.43864AϾG CTGTAACCC Intron 14 124 0.0 88 1.1 72 2.8 284 1.1 73 TAGCACACC g.43938GϾA ACTGTCTAC Exon 15 R590Q 124 0.8 88 0.0 74 0.0 286 0.3 35 GCTGCCACT g.48606AϾG GAATGGCCC Exon 16 R652G 124 7.3 86 2.3 74 1.4 284 4.2 36 GCTACAATT g.48771AϾG TTGAAATTC Intron 16 114 5.3 86 2.3 70 1.4 270 3.3 37 TTGCAAACA g.51576CϾT CACATAACA Intron 17 122 95.1 70 74.3 80 71.3 272 82.7 38 TTACATAAC g.56969AϾG TGGTTTTAG Intron 20 126 6.3 60 3.3 66 1.5 252 4.4 74 ATATTTTAC g.58304TϾC GTATTAATG Intron 21 124 0.0 96 0.0 92 1.1 212 0.3 39 CTGTATTAA g.58312TϾC GTCTAGAAC Intron 21 122 4.1 96 1.0 92 1.1 310 2.3 75 AAAGGAGGC g.63395delT GAAGAGATG Intron 22 124 0.8 92 0.0 94 0.0 310 0.3 76 AATATTAAG g.63598AϾT TTATTCTAT Intron 23 124 0.0 92 1.1 94 0.0 310 0.3 40 ATGGTCAAG g.68988AϾG AGCAAAGAA Exon 26 E1099G 112 1.8 92 0.0 84 0.0 288 0.7 41 TATTTATAA g.72169TϾC TTGGTTAAC Intron 26 122 91.8 90 65.6 92 75.0 304 78.9 42 GTAACATTT g.73092TϾC CAAATTTAC Intron 27 124 7.3 94 1.1 86 1.2 304 3.6 n, number of alleles analyzed (number of subjects times 2). 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67 ABCB11 p.Val444Ala
X
ABCB11 p.Val444Ala 16763017:67:4868
status: NEW
view ABCB11 p.Val444Ala details
ABCB11 p.Met677Val
X
ABCB11 p.Met677Val 16763017:67:5460
status: NEW
view ABCB11 p.Met677Val details
ABCB11 p.Arg698His
X
ABCB11 p.Arg698His 16763017:67:5544
status: NEW
view ABCB11 p.Arg698His details
ABCB11 p.Val284Ala
X
ABCB11 p.Val284Ala 16763017:67:3812
status: NEW
view ABCB11 p.Val284Ala details
ABCB11 p.Thr619Ala
X
ABCB11 p.Thr619Ala 16763017:67:5292
status: NEW
view ABCB11 p.Thr619Ala details
ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:67:5208
status: NEW
view ABCB11 p.Arg616Gly details
ABCB11 p.Arg299Lys
X
ABCB11 p.Arg299Lys 16763017:67:3895
status: NEW
view ABCB11 p.Arg299Lys details
ABCB11 p.Ile206Val
X
ABCB11 p.Ile206Val 16763017:67:3645
status: NEW
view ABCB11 p.Ile206Val details
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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108 ABCB11 p.Ala865Val
X
ABCB11 p.Ala865Val 16763017:108:326
status: NEW
view ABCB11 p.Ala865Val details
ABCB11 p.Arg958Gln
X
ABCB11 p.Arg958Gln 16763017:108:730
status: NEW
view ABCB11 p.Arg958Gln details
Of 19 genetic variants in coding and noncoding exons, 8 TABLE 4 Continued Variant ID 5Ј Sequence Genetic Variation 3Ј Sequence Region Amino Acid Change CA AA JA Total n % n % n % n 48 TTTTGTAGC g.73233AϾG ATGGGCTGT Exon 20 A804A 200 0.0 66 93.9 96 0.0 362 1.1 49 CTACAGATG g.73505CϾT TTCCCAAGT Exon 21 A865V 178 0.0 74 0.0 82 2.4 334 0.6 73 TGGGAGGGG g.73539AϾC AATAGAAGT Intron 21 176 0.6 74 0.0 84 0.0 334 0.3 74 TGGTAAAAG g.81650CϾT GACTGTGTG Intron 21 196 0.0 86 1.2 94 0.0 376 0.3 75 GTCACGAAA g.82653GϾA GAGTTATTT Intron 22 136 0.0 90 0.0 46 2.2 272 0.4 50 GTTATTTCT g.82665GϾA CCCTTGTAT Intron 22 202 0.0 92 6.5 82 0.0 376 1.6 76 AGGAGAGGC g.82759GϾA GTTCATTGA Exon 23 R958Q 202 0.0 92 0.0 94 1.1 388 0.3 77 CAATATTTA g.82829CϾT GGATTCTGC Exon 23 Y981Y 200 0.0 92 1.1 94 0.0 386 0.3 78 GTTTATTGC g.82871GϾA AATTCTGCT Exon 23 A995A 200 0.0 92 1.1 94 0.0 386 0.3 51 ACTGAGTGC g.85620AϾG ACAGCTCTT Exon 24 A1028A 194 54.1 76 26.3 90 47.8 360 47.8 79 CTATGCAGC g.85774CϾA ATAAAAAAG Intron 24 194 0.0 76 0.0 90 1.1 360 0.3 80 GCAAACTAA g.85848CϾG ACAAGAACA Intron 24 194 0.0 76 1.3 90 0.0 360 0.3 52 TAAATTTAC g.87308AϾG TATCCTTCT Exon 25 T1086T 186 0.0 76 7.9 82 0.0 344 1.7 53 CAATCATGC g.94270AϾG TCTTTGCAT Intron 27 172 55.2 64 75.0 94 51.1 330 48.2 81 CCAGAACGC g.94387GϾA GATATCATT Exon 28 A1283A 194 0.0 64 0.0 94 1.1 352 0.3 82 TCCCAGCAG g.94582GϾA AGGGATTGT Exon 28 192 0.0 26 0.0 88 1.1 306 0.3 n, number of alleles analyzed (number of subjects times 2); %, allele frequencies for Caucasians (CA), African Americans (AA), and Japanese (JA). Login to comment
110 ABCB4 p.Thr175Ala
X
ABCB4 p.Thr175Ala 16763017:110:201
status: NEW
view ABCB4 p.Thr175Ala details
ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:110:210
status: NEW
view ABCB4 p.Arg652Gly details
These included three Caucasian variants in exon 6 (c.523AϾG; allele frequency 3.2%), exon 16 (c.1954AϾG; 7.3%), and exon 26 (c.3296AϾG; 1.8%), resulting in amino acid substitutions p.T175A, p.R652G, and p.E1099G, respectively. Login to comment
111 ABCB4 p.Arg590Gln
X
ABCB4 p.Arg590Gln 16763017:111:259
status: NEW
view ABCB4 p.Arg590Gln details
ABCB4 p.Pro95Ser
X
ABCB4 p.Pro95Ser 16763017:111:276
status: NEW
view ABCB4 p.Pro95Ser details
ABCB4 p.Asp87Glu
X
ABCB4 p.Asp87Glu 16763017:111:268
status: NEW
view ABCB4 p.Asp87Glu details
ABCB4 p.Ile367Val
X
ABCB4 p.Ile367Val 16763017:111:250
status: NEW
view ABCB4 p.Ile367Val details
ABCB4 p.Glu450Gly
X
ABCB4 p.Glu450Gly 16763017:111:288
status: NEW
view ABCB4 p.Glu450Gly details
Five rare missense mutations occurred once as single heterozygotes (singletons) in exon 4 (c.261TϾC and c.283CϾT), exon 10 (c.1099AϾG), exon 12 (c.1349AϾG), and exon 15 (c.1769GϾA), resulting in the amino acid changes p.I367V, p.R590Q, p.D87E, p.P95S, and p.E450G. Login to comment
116 ABCB11 p.Val444Ala
X
ABCB11 p.Val444Ala 16763017:116:141
status: NEW
view ABCB11 p.Val444Ala details
ABCB11 p.Ala865Val
X
ABCB11 p.Ala865Val 16763017:116:412
status: NEW
view ABCB11 p.Ala865Val details
ABCB11 p.Met677Val
X
ABCB11 p.Met677Val 16763017:116:153
status: NEW
view ABCB11 p.Met677Val details
ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:116:302
status: NEW
view ABCB11 p.Arg616Gly details
Two Caucasian-specific variants in exon 13 (c.1331TϾC; 59.4%) and exon 17 (c.2029AϾG; 4.2%) coded for amino acid substitutions p.V444A and p.M677V; one variant, detected in exon 16 (c.1846CϾG, 2.2%) in the African-American population sample, resulted in protein sequence alteration p.R616G; and the Japanese-specific exon 21 variant c.2594CϾT (2.4%) resulted in amino acid substitution p.A865V (Table 4). Login to comment
117 ABCB11 p.Arg698His
X
ABCB11 p.Arg698His 16763017:117:195
status: NEW
view ABCB11 p.Arg698His details
ABCB11 p.Thr619Ala
X
ABCB11 p.Thr619Ala 16763017:117:158
status: NEW
view ABCB11 p.Thr619Ala details
ABCB11 p.Arg299Lys
X
ABCB11 p.Arg299Lys 16763017:117:123
status: NEW
view ABCB11 p.Arg299Lys details
ABCB11 p.Ile206Val
X
ABCB11 p.Ile206Val 16763017:117:59
status: NEW
view ABCB11 p.Ile206Val details
ABCB11 p.Arg958Gln
X
ABCB11 p.Arg958Gln 16763017:117:236
status: NEW
view ABCB11 p.Arg958Gln details
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). Login to comment
143 ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:143:24
status: NEW
view ABCB11 p.Arg616Gly details
ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:143:405
status: NEW
view ABCB11 p.Arg616Gly details
In particular, ABCB11 p.R616G is suspicious for changing the physicochemical properties of the resulting protein (highest Grantham score of 125), is probably deleterious according to the low SIFT value (0.01), is supposed to affect protein function because of its high PSIC score, and is evolutionarily less favorable considering the negative BLOSUM62 value, although sequence alignments indicated that p.R616G is located in a probably less deleterious, evolutionarily unconserved region. Login to comment
144 ABCB11 p.Thr619Ala
X
ABCB11 p.Thr619Ala 16763017:144:39
status: NEW
view ABCB11 p.Thr619Ala details
Similarly, ABCB4 p.E1009G and ABCB11 p.T619A have more radical Grantham scores, are less tolerated substitutions (SIFT) with possibly damaging effect (PSIC), and are evolutionary less acceptable but located in an evolutionary unconserved region. Login to comment
145 ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:145:21
status: NEW
view ABCB4 p.Arg652Gly details
In contrast, ABCB4 p.R652G is a more common variant, which changes an evolutionary conserved amino acid to an evolutionary less acceptable one with probably altered physicochemical properties. Login to comment
146 ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:146:106
status: NEW
view ABCB4 p.Arg652Gly details
On the other hand, SIFT and PSIC scores of this variant do not confirm functional consequences of ABCB4 p.R652G. Login to comment
163 ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:163:8
status: NEW
view ABCB4 p.Arg652Gly details
ABCB4 p.R652G was the only protein-altering variant with high allele frequency in all groups (7.2% in Caucasian, 1.4% in Japanese, and 2.3% in Korean). Login to comment
164 ABCB4 p.Thr175Ala
X
ABCB4 p.Thr175Ala 16763017:164:8
status: NEW
view ABCB4 p.Thr175Ala details
ABCB4 p.T175A (3.2%) and p.E1099G (1.8%) were only present in the Caucasian sample. Login to comment
166 ABCB11 p.Val444Ala
X
ABCB11 p.Val444Ala 16763017:166:59
status: NEW
view ABCB11 p.Val444Ala details
ABCB11 p.Ala865Val
X
ABCB11 p.Ala865Val 16763017:166:223
status: NEW
view ABCB11 p.Ala865Val details
ABCB11 p.Met677Val
X
ABCB11 p.Met677Val 16763017:166:120
status: NEW
view ABCB11 p.Met677Val details
The most common ABCB11 protein-altering polymorphism was p.V444A, which was frequently observed in all groups [ABCB11 p.M677V was present in both the Caucasian (4.2%,) and the African-American (14%) population sample and p.A865V was only found in Japanese samples]. Login to comment
177 ABCB11 p.Val444Ala
X
ABCB11 p.Val444Ala 16763017:177:379
status: NEW
view ABCB11 p.Val444Ala details
ABCB11 p.Ala865Val
X
ABCB11 p.Ala865Val 16763017:177:503
status: NEW
view ABCB11 p.Ala865Val details
ABCB11 p.Met677Val
X
ABCB11 p.Met677Val 16763017:177:455
status: NEW
view ABCB11 p.Met677Val details
ABCB11 p.Arg698His
X
ABCB11 p.Arg698His 16763017:177:479
status: NEW
view ABCB11 p.Arg698His details
ABCB11 p.Val284Ala
X
ABCB11 p.Val284Ala 16763017:177:330
status: NEW
view ABCB11 p.Val284Ala details
ABCB11 p.Thr619Ala
X
ABCB11 p.Thr619Ala 16763017:177:430
status: NEW
view ABCB11 p.Thr619Ala details
ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:177:404
status: NEW
view ABCB11 p.Arg616Gly details
ABCB11 p.Arg299Lys
X
ABCB11 p.Arg299Lys 16763017:177:355
status: NEW
view ABCB11 p.Arg299Lys details
ABCB11 p.Ile206Val
X
ABCB11 p.Ile206Val 16763017:177:306
status: NEW
view ABCB11 p.Ile206Val details
ABCB11 p.Arg958Gln
X
ABCB11 p.Arg958Gln 16763017:177:527
status: NEW
view ABCB11 p.Arg958Gln details
ABCB4 p.Arg590Gln
X
ABCB4 p.Arg590Gln 16763017:177:225
status: NEW
view ABCB4 p.Arg590Gln details
ABCB4 p.Thr175Ala
X
ABCB4 p.Thr175Ala 16763017:177:151
status: NEW
view ABCB4 p.Thr175Ala details
ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:177:249
status: NEW
view ABCB4 p.Arg652Gly details
ABCB4 p.Pro95Ser
X
ABCB4 p.Pro95Ser 16763017:177:127
status: NEW
view ABCB4 p.Pro95Ser details
ABCB4 p.Asp87Glu
X
ABCB4 p.Asp87Glu 16763017:177:104
status: NEW
view ABCB4 p.Asp87Glu details
ABCB4 p.Ile367Val
X
ABCB4 p.Ile367Val 16763017:177:176
status: NEW
view ABCB4 p.Ile367Val details
ABCB4 p.Glu450Gly
X
ABCB4 p.Glu450Gly 16763017:177:200
status: NEW
view ABCB4 p.Glu450Gly details
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). Login to comment
236 ABCB11 p.Val444Ala
X
ABCB11 p.Val444Ala 16763017:236:178
status: NEW
view ABCB11 p.Val444Ala details
With respect to the reference sequence, ABCB11_3, ABCB11_4, ABCB11_5, ABCB11_6, ABCB11_11 ABCB11_37, and ABCB11_38 contain one nonsynonymous cSNP (c.1331TϾC) in exon 13 (p.V444A) and three to four linked intronic SNPs in introns 9, 13, and 14, and 20 as a common denominator. Login to comment
271 ABCB4 p.Thr175Ala
X
ABCB4 p.Thr175Ala 16763017:271:106
status: NEW
view ABCB4 p.Thr175Ala details
ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:271:272
status: NEW
view ABCB4 p.Arg652Gly details
Only two variants from our study had been related to cholestatic disease earlier, ABCB4 c.523AϾG (p.T175A), the second most prevalent nonsynonymous change in Caucasians (Rosmorduc et al., 2001), and the most prevalent nonsynonymous variant, ABCB4 c.1954GϾA (p.R652G), which was present in all of our population samples (Jacquemin et al., 2001). Login to comment
283 ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:283:33
status: NEW
view ABCB4 p.Arg652Gly details
For instance, the MDR3 variant p.R652G was present in PFIC3 patients and healthy subjects and hence cannot, alone, be sufficient to cause cholestasis. Login to comment
284 ABCB4 p.Arg652Gly
X
ABCB4 p.Arg652Gly 16763017:284:24
status: NEW
view ABCB4 p.Arg652Gly details
It was suggested that p.R652G had no or mild consequences under normal conditions, but resulted in cholestasis during pregnancy (Jacquemin et al., 2001). Login to comment
286 ABCB11 p.Glu297Gly
X
ABCB11 p.Glu297Gly 16763017:286:185
status: NEW
view ABCB11 p.Glu297Gly details
ABCB11 p.Arg432Thr
X
ABCB11 p.Arg432Thr 16763017:286:210
status: NEW
view ABCB11 p.Arg432Thr details
ABCB11 p.Lys930*
X
ABCB11 p.Lys930* 16763017:286:101
status: NEW
view ABCB11 p.Lys930* details
A splicing mutation (ϩ3)AϾC (intron 4) combined with a frameshift mutation in exon 22 (p.K930X), resulting in a PFIC2 phenotype and two nonsynonymous variants in exon 9 (p. E297G) and in exon 12 (p.R432T), were encountered in the patient exhibiting a BRIC (benign recurrent intrahepatic cholestasis) phenotype. Login to comment
296 ABCB11 p.Thr619Ala
X
ABCB11 p.Thr619Ala 16763017:296:121
status: NEW
view ABCB11 p.Thr619Ala details
ABCB11 p.Arg616Gly
X
ABCB11 p.Arg616Gly 16763017:296:108
status: NEW
view ABCB11 p.Arg616Gly details
ABCB4 p.Arg590Gln
X
ABCB4 p.Arg590Gln 16763017:296:81
status: NEW
view ABCB4 p.Arg590Gln details
Although experimentally not validated, we conclude that the amino acid changes p.R590Q, p.E1099G (ABCB4), p.R616G, and p.T619A (ABCB11) are the strongest candidates to alter protein function and subsequently biliary excretion (Table 5). Login to comment