ABCC3 p.Ala1513Asp
| Predicted by SNAP2: | C: N (97%), D: N (97%), E: N (97%), F: N (72%), G: N (97%), H: N (97%), I: N (97%), K: N (97%), L: N (97%), M: N (97%), N: N (97%), P: N (93%), Q: N (97%), R: N (97%), S: N (97%), T: N (97%), V: N (97%), W: N (61%), Y: N (72%), |
| Predicted by PROVEAN: | C: N, D: N, E: N, F: D, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] Pharmacogenomics of MRP transporters (ABCC1-5) and... Drug Metab Rev. 2008;40(2):317-54. Gradhand U, Kim RB
Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2).
Drug Metab Rev. 2008;40(2):317-54., [PMID:18464048]
Abstract [show]
Elucidation of the key mechanisms that confer interindividual differences in drug response remains an important focus of drug disposition and clinical pharmacology research. We now know both environmental and host genetic factors contribute to the apparent variability in drug efficacy or in some cases, toxicity. In addition to the widely studied and recognized genes involved in the metabolism of drugs in clinical use today, we now recognize that membrane-bound proteins, broadly referred to as transporters, may be equally as important to the disposition of a substrate drug, and that genetic variation in drug transporter genes may be a major contributor of the apparent intersubject variation in drug response, both in terms of attained plasma and tissue drug level at target sites of action. Of particular relevance to drug disposition are members of the ATP Binding Cassette (ABC) superfamily of efflux transporters. In this review a comprehensive assessment and annotation of recent findings in relation to genetic variation in the Multidrug Resistance Proteins 1-5 (ABCC1-5) and Breast Cancer Resistance Protein (ABCG2) are described, with particular emphasis on the impact of such transporter genetic variation to drug disposition or efficacy.
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No. Sentence Comment
172 Figure 3 Predicted membrance topology of MRP3 (ABCC3) based on hydrophobicity analysis. Locations of the non-synonymous polymorphisms are indicated with arrows. See Table 3 for allele frequencies and description of funtional consequences. NH2 COOH NBD NBD in out Membrane Gly11Asp His68Tyr Ser346Phe Lys13Asn Gln513Lys Thr527Arg Ala528Gly Leu548Gln Gln741* Val799Met Gln933Arg_fs Ser1219Arg Arg1297His Pro1300Leu Leu1362Val Ala1398Val Thr1406Met Gly1423Arg Ala1513Asp MRP3 (ABCC3) NBD NBD Lys13Asn NBD NBD Lys13Asn In accordance with the latter finding, Gradhand et al. (2007b) found no impact of the -211C>T polymorphism on the ABCC3 promoter activity in transfected cell lines.
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ABCC3 p.Ala1513Asp 18464048:172:457
status: NEW174 For example, changing the tryptophan at position 1242 of MRP3 markedly altered the substrate specificity of MRP3 (Oleschuk et al., 2003), as is the case when a similar Table 3 MRP3 (ABCC3) single nucleotide polymorphisms. Location, allele frequency and functional effects. Position in coding sequence Amino acid exchange Location Allele frequency Effect NCBI ID ReferenceAf Ca Jp others 32G>A Gly11Asp Exon 1 - 0 [1] 0.6 [2] - - rs11568609 39G>C Lys13Asn Exon1 - 0.5 [1] 0 [3] - no effect on mRNA or protein in liver [1] 0 [2] 202C>T His68Tyr Exon2 - 1.6 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1037C>T Ser346Phe Exon9 - 0.5 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1537C>A Gln513Lys Exon12 - 0.5 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1580C>G Thr527Arg Exon 12 - - - - - rs1003354 1583C>G Ala528Gly Exon 12 - - - - - rs1003355 1643T>A Leu548Gln Exon 13 - 0.3 [4] 0 [3] 0 [2] - - 2221C>T Gln741* Exon 17 - 0 [1] 0.6 [2] - - 2395G>A Val799Met Exon 18 - 0 [1] 0.6 [2] - - 2798A-2799G del Gln933Arg_fs Exon 21 - 0 [1] 0.6 [2] - frame shift and early stop codon [2] 3657C>A Ser1219Arg Exon 25 - 0 [1] 1.1 [2] - no effect on expression, localization or transport in vesicles from transfected cells [4] 3890G>A Arg1297His Exon27 - 5.2 [1] 8 [4] 0 [3] 0 [2] - no effect on mRNA or protein in liver [1] 3899C>T Pro1300Leu Exon 27 - - - - - rs41280128 4084C>G Leu1362Val Exon 28 - - - - - rs1051625 4193C>T Ala1398Val Exon29 - - - - - rs11549764 4217C>T Thr1406Met Exon29 - 0 [1] 0.6 [2] - - 4267G>A Gly1423Arg Exon29 - 12.5 [1] 0 [3] - no effect on mRNA or protein in liver [1] 0 [2] 4538A>C Ala1513Asp Exon 31 - - - - - rs11656685 1.
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ABCC3 p.Ala1513Asp 18464048:174:1641
status: NEW