ABCD1 p.Ala61Gly
| Predicted by SNAP2: | C: N (78%), D: N (93%), E: N (93%), F: N (87%), G: N (97%), H: N (87%), I: N (93%), K: N (97%), L: N (93%), M: N (93%), N: N (97%), P: N (93%), Q: N (97%), R: N (97%), S: N (97%), T: N (97%), V: N (93%), W: N (57%), Y: N (66%), |
| Predicted by PROVEAN: | 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, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] ABC drug transporters: hereditary polymorphisms an... Pharmacogenomics. 2001 Feb;2(1):51-64. Kerb R, Hoffmeyer S, Brinkmann U
ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2.
Pharmacogenomics. 2001 Feb;2(1):51-64., [PMID:11258197]
Abstract [show]
Transport by ATP-dependent efflux pumps, such as P-glycoprotein (PGP) and multi-drug resistance related proteins (MRPs), influences bioavailability and disposition of drugs. These efflux pumps serve as defence mechanisms and determine bioavailability and CNS concentrations of many drugs. However, despite the fact that substantial data have been accumulated on the structure, function and pharmacological role of ABC transporters and even though modification of PGP function is an important mechanism of drug interactions and adverse effects in humans, there is a striking lack of data on variability of the underlying genes. This review focuses on the human drug transporter proteins PGP (MDR1) and the multi-drug resistance proteins MRP1 and MRP2. An overview is provided of pharmacologically relevant genetic, structural and functional data as well as on hereditary polymorphisms, their phenotypical consequences and pharmacological implications.
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No. Sentence Comment
97 SNP Region N Frequency of SNPs (%) Effect Heterozygous Homozygous Observed Estimated T-12C E1 85 11.8 0 0.4 Non-coding G-1A E2 188 11.2 0 0.4 TL initiation A61G E2 188 17.6 0.5 0.81 Asn21Asp G-25T I4 85 26 3.5 2.3 G-35C I4 85 1.2 0 0.01 # T307C E5 85 1.2 0 0.01 Phe103Leu C+139T I5 85 48.2 16.5 16.8 C+145T I5 85 2.4 0 0.01 G1199A E11 85 12.9 0 0.4 Ser400Asn C1236T E12 188 48.9 13.3 14.4 Gly412Gly # C+44T I12 188 11.7 0 0.4 T-76A I16 85 45.9 22.4 20.3 A+137G I17 85 1.2 0 0.01 G2677T E21 83b 43.4 42.2 38.4 Ala893Ser G2995A E24 36b 11.1 38.4 Ala999Thr C3435T E26 537 47.7 26.4 24.1 Ile1145Ile C3396T E26 188 0.53 0 0.01 Wobble § MDR1 sequences gb:AC002457 and AC005068 are defined as 'wild type`.
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ABCD1 p.Ala61Gly 11258197:97:156
status: NEW106 A61G leads to the replacement of Asn by Asp at position 21 resulting in a net charge change (basic to acidic) close to the N-terminus of PGP.
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ABCD1 p.Ala61Gly 11258197:106:0
status: NEW[hide] Genetic polymorphisms of the human MDR1 drug trans... Annu Rev Pharmacol Toxicol. 2003;43:285-307. Epub 2002 Jan 10. Schwab M, Eichelbaum M, Fromm MF
Genetic polymorphisms of the human MDR1 drug transporter.
Annu Rev Pharmacol Toxicol. 2003;43:285-307. Epub 2002 Jan 10., [PMID:12359865]
Abstract [show]
P-glycoprotein is an ATP-dependent efflux pump that contributes to the protection of the body from environmental toxins. It transports a huge variety of structurally diverse compounds. P-glycoprotein is involved in limiting absorption of xenobiotics from the gut lumen, in protection of sensitive tissues (brain, fetus, testis), and in biliary and urinary excretion of its substrates. P-glycoprotein can be inhibited or induced by xenobiotics, thereby contributing to variable drug disposition and drug interactions. Recently, several SNPs have been identified in the MDR1 gene, some of which can affect P-glycoprotein expression and function. Potential implications of MDR1 polymorphisms for drug disposition, drug effects, and disease risk are discussed.
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No. Sentence Comment
52 The SNPs at positions A61G (Asn21Asp), C1236T, and C3435T had been reported previously (23, 26).
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ABCD1 p.Ala61Gly 12359865:52:22
status: NEW68 The A61G mutation (Asn21Asp) results in a net charge change (basic to acidic) close to the N-terminus of P-glycoprotein, which appears to be of minor functional importance if recombinant mutational analyses of P-glycoprotein are considered (6).
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ABCD1 p.Ala61Gly 12359865:68:4
status: NEW