ABCMdb

PMID: 12893986

Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, DeYoung J, Taylor T, Carlson EJ, Herskowitz I, Giacomini KM, Clark AG
Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene.
Pharmacogenetics. 2003 Aug;13(8):481-94., [PubMed]

Sentences

No. Mutations Sentence Comment

103 ABCB1 p.Pro1051Ala ABCB1 p.Arg669Cys ABCB1 p.Thr1256Lys ABCB1 p.Leu662Arg ABCB1 p.Val1251Ile ABCB1 p.Ile849Met ABCB1 p.Met89Thr ABCB1 p.Trp1108Arg A total of 30 segregating sites have not been previously described, including eight non-synonymous changes coding for the following amino acid changes: Met89Thr, Leu662Arg, Arg669Cys, Ile849Met, Pro1051Ala, Trp1108Arg, Val1251Ile, and Thr1256Lys. Login to comment 111 ABCB1 p.Ser1141Thr ABCB1 p.Pro1051Ala ABCB1 p.Thr1256Lys ABCB1 p.Leu662Arg ABCB1 p.Ile261Val These ten variants included five non-synonymous sites (Ile261Val, Leu662Arg, Pro1051Ala, Ser1141Thr, and Thr1256Lys). Login to comment 113 ABCB1 p.Arg669Cys ABCB1 p.Val1251Ile ABCB1 p.Ile849Met ABCB1 p.Trp1108Arg An additional five coding variants occurred at sites that were conserved in six of the seven species, including those resulting in the Arg669Cys, Ile849Met, Trp1108Arg, and Val1251Ile changes. Login to comment 141 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Pro1051Ala ABCB1 p.Arg669Cys ABCB1 p.Thr1256Lys ABCB1 p.Leu662Arg ABCB1 p.Val1251Ile ABCB1 p.Ile849Met ABCB1 p.Met89Thr ABCB1 p.Trp1108Arg ABCB1 p.Ile261Val Unauthorized reproduction of this article is prohibited. Table 1 Genetic variation in ABCB1 Allele frequencyd Variant cDNA NT DNA/AA AA Total CA AA AS ME PA No.a positionb changec position change (n ¼ 494) (n ¼ 200) (n ¼ 200) (n ¼ 60) (n ¼ 20) (n ¼ 14) 1.1Ã (À274) G to A Intron À1 0.006 0 0.016 0 0 0 1.2Ã (À223) C to T Intron À1 0.002 0.005 0 0 0 0 1.3Ã (À146) T to C Intron À1 0.002 0 0.005 0 0 0 1.4Ã (À60) A to T Intron À1 0.004 0 0.010 0 0 0 1.5 (À41) A to G Intron À1 0.002 0 0 0.017 0 0 1.6Ã À241 G to A Non-coding 0.002 0 0 0.017 0 0 1.7 À145 C to G Non-coding 0.002 0 0 0.017 0 0 1.8 À129 T to C Non-coding 0.060 0.051 0.071 0.036 0.100 0.071 1.9 À43 A to G Non-coding 0.012 0 0.020 0.036 0 0 1.10Ã (+140) C to A Intron 1 0.013 0.005 0.021 0 0 0.071 1.11Ã (+237) G to A Intron 1 0.004 0 0.010 0 0 0 2.1 À4 C to T Non-coding 0.004 0 0.010 0 0 0 2.2 À1 G to A Non-coding 0.036 0.080 0.005 0 0.050 0 2.3 61 A to G 21 Asn to Asp 0.045 0.080 0.025 0.017 0 0 4.1Ã (À8) C to G Intron 3 0.002 0.005 0 0 0 0 4.2Ã 266 T to C 89 Met to Thr 0.002 0.005 0 0 0 0 5.1 (À25) G to T Intron 4 0.210 0.158 0.300 0.067 0.200 0.286 8.1 729 A to G 243 Syn 0.002 0.005 0 0 0 0 8.2Ã 781 A to G 261 Ile to Val 0.006 0 0.015 0 0 0 10.1Ã (À44) A to G Intron 9 0.400 0.450 0.255 0.685 0.450 0.571 11.1Ã (À41) T to G Intron 10 0.002 0 0 0.017 0 0 11.2 1199 G to A 400 Ser to Asn 0.014 0.025 0.010 0 0 0 12.1Ã (À4) G to A Intron 11 0.002 0 0.005 0 0 0 12.2 1236 C to T 412 Syn 0.385 0.459 0.209 0.685 0.450 0.571 12.3Ã 1308 A to G 436 Syn 0.002 0 0.005 0 0 0 12.4Ã (+17) G to A Intron 12 0.008 0 0.020 0 0 0 12.5 (+44) C to T Intron 12 0.088 0.046 0.168 0 0 0 13.1 (+24) C to T Intron 13 0.530 0.521 0.542 0.540 0.450 0.571 14.1 1617 C to T 539 Syn 0.002 0.005 0 0 0 0 14.2 (+38) A to G Intron 14 0.540 0.505 0.540 0.683 0.450 0.500 15.1 (+38) G to A Intron 15 0.004 0.005 0.005 0 0 0 16.1Ã 1985 T to G 662 Leu to Arg 0.002 0.005 0 0 0 0 16.2Ã 2005 C to T 669 Arg to Cys 0.004 0 0.010 0 0 0 18.1Ã (À27) A to G Intron 17 0.008 0.010 0.005 0 0.050 0 20.1Ã (+8) C to G Intron 20 0.002 0 0.005 0 0 0 20.2 (+24) G to A Intron 20 0.126 0.121 0.150 0.067 0.200 0 20.3Ã (+40) C to T Intron 20 0.014 0 0.035 0 0 0 21.1Ã 2547 A to G 849 Ile to Met 0.002 0.005 0 0 0 0 21.2 2650 C to T 884 Syn 0.004 0.005 0.005 0 0 0 21.3a 2677 G to T 893 Ala to Ser 0.308 0.464 0.100 0.450 0.400 0.357 21.3b 2677 G to A 893 Ala to Thr 0.035 0.036 0.005 0.067 0 0.357 22.1 (+31) G to A Intron 22 0.002 0 0.005 0 0 0 25.1Ã 3151 C to G 1051 Pro to Ala 0.002 0 0.005 0 0 0 26.1Ã 3322 T to C 1108 Trp to Arg 0.002 0 0.005 0 0 0 26.2 3421 T to A 1141 Ser toThr 0.047 0 0.111 0 0.050 0 26.3 3435 C to T 1145 Syn 0.392 0.561 0.202 0.400 0.500 0.500 28.1 3751 G to A 1251 Val to Ile 0.002 0 0 0 0.050 0 28.2 3767 C to A 1256 Thr to Lys 0.002 0.005 0 0 0 0 28.3 (+21) T to C Intron 28 0.031 0 0.077 0 0 0 a Variants are numbered sequentially by exon. Login to comment 156 ABCB1 p.Asn21Asp Only two haplotypes (ABCB1Ã14 and ABCB1Ã14A) contain two non-synonymous changes (Asn21Asp and Ala893Ser). Login to comment 164 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Thr1256Lys ABCB1 p.Leu662Arg ABCB1 p.Val1251Ile ABCB1 p.Ile849Met ABCB1 p.Met89Thr ABCB1 p.Ile261Val M89T I849M V1251I T1256K S1141TW1108R P1052AR669C A893S/T L662R Cytoplasm S400N I261V N21D Extracellular Fig. 1. Login to comment 301 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Phe103Leu Other non-synonymous variants (Asn21Asp, Phe103Leu, Ser400Asn, and Ala998Thr) have also been shown not to affect P-glycoprotein function [43]. Login to comment