ABCA1 p.Met1091Leu
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PMID: 16429166
[PubMed]
Brunham LR et al: "Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene."
No.
Sentence
Comment
63
To determine whether the severe phenotype conferred by the M1091T mutation is a result of the sensitivity of this site, or rather is specific to the insertion of the threonine residue, we generated and characterized cell lines transfected with plasmids bearing M1091L and M1091V alleles, both predicted to have no impact on ABCA1 function (subPSEC scores À2.65 and À2.71, respectively).
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ABCA1 p.Met1091Leu 16429166:63:261
status: NEW87 (B) Cholesterol efflux was assessed in 293 cells stably transfected with wild-type, M1091T, M1091L, or M1091V ABCA1 alleles.
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ABCA1 p.Met1091Leu 16429166:87:92
status: NEW139 In addition, both the M1091V and M1091L substitutions severely impaired the function of ABCA1, yet they were predicted to be functionally neutral.
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ABCA1 p.Met1091Leu 16429166:139:33
status: NEW142 Therefore, when calculating amino acid probabilities for position 1091, the subPSEC method includes sequences from only ABCA1 and ABCA4, which represents enough sequence variability to predict that a relatively radical mutation such as M1091T will likely be deleterious but not enough to predict that relatively conservative mutations such as M1091L or M1091V will be deleterious.
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ABCA1 p.Met1091Leu 16429166:142:343
status: NEW143 Our experimental finding that M1091L severely impairs ABCA1 cholesterol efflux suggests that substitution of leucine for methionine at this position may have played an important role in the functional divergence of ABCA7 from ABCA1.
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ABCA1 p.Met1091Leu 16429166:143:30
status: NEW