ABCC2 p.Leu849Met
| Predicted by SNAP2: | A: D (80%), C: D (71%), D: D (91%), E: D (91%), F: D (80%), G: D (91%), H: D (91%), I: D (59%), K: D (80%), M: D (53%), N: D (85%), P: D (91%), Q: D (80%), R: D (53%), S: D (85%), T: D (85%), V: D (59%), W: D (85%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Potential impact of ABCB1 (p-glycoprotein) polymor... Arch Toxicol. 2007 Aug;81(8):553-63. Epub 2007 Mar 13. Macdonald N, Gledhill A
Potential impact of ABCB1 (p-glycoprotein) polymorphisms on avermectin toxicity in humans.
Arch Toxicol. 2007 Aug;81(8):553-63. Epub 2007 Mar 13., [PMID:17354009]
Abstract [show]
Several members of the ATP binding cassette (ABC) transporter protein superfamily perform xenobiotic efflux functions in mammals, limiting gut absorption, mediating excretion, and controlling entry of a wide range of chemicals to sensitive compartments such as brain, testes and foetus. Perhaps the best characterised of these is p-glycoprotein (gene name ABCB1/MDR1), a barrier epithelia expressed protein with structurally diverse substrates, including the avermectin pesticides. In specific mouse and dog strains, ABCB1 mutations have been identified that result in loss of p-glycoprotein function in the blood brain barrier (BBB) and increased susceptibility to avermectin neurotoxicity. As yet no large rearrangements of the human ABCB1 gene analogous to those in the mouse and dog have been identified. However, numerous human ABCB1 single nucleotide polymorphisms (SNPs) have been identified, the allelic frequencies of which vary with ethnicity. There is no clear consensus on whether or not SNPs, or combinations of SNPs, reduce human p-glycoprotein functionality. However, recent in vivo human data indicate that the two commonest ABCB1 haplotypes both exhibit full BBB functionality. We discuss here the role of p-glycoprotein in limiting brain absorption of avermectin pesticides, as well as the potential impact of the reported functional effects and population frequencies of known ABCB1 polymorphisms on avermectin pesticide risk assessments.
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No. Sentence Comment
132 Only two known human SNP results in change of an amino acid in a transmembrane domain, A2547G which results in substitution of a methionine in place of leucine 849 (Kroetz et al. 2003), and A2956G which results in substitution of valine in place of methionine at amino acid 986 (Tanabe et al. 2001).
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ABCC2 p.Leu849Met 17354009:132:129
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