ABCA1 p.Leu144Arg
| Predicted by SNAP2: | A: D (53%), C: N (66%), D: D (80%), E: D (75%), F: N (78%), G: D (80%), H: D (66%), I: N (87%), K: D (75%), M: N (78%), N: D (66%), P: D (71%), Q: D (71%), R: D (75%), S: D (66%), T: N (53%), V: N (87%), W: D (71%), Y: D (59%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, F: N, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: N, T: N, V: N, W: D, Y: N, |
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[hide] Role of apoA-I, ABCA1, LCAT, and SR-BI in the biog... J Mol Med (Berl). 2006 Apr;84(4):276-94. Epub 2006 Feb 25. Zannis VI, Chroni A, Krieger M
Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL.
J Mol Med (Berl). 2006 Apr;84(4):276-94. Epub 2006 Feb 25., [PMID:16501936]
Abstract [show]
The concentration, composition, shape, and size of plasma high-density lipoprotein (HDL) are determined by numerous proteins that influence its biogenesis, remodeling, and catabolism. The discoveries of the HDL receptor (scavenger receptor class B type I, SR-BI) and the ABCA1 (ATP-binding cassette transporter A1) lipid transporter provided two missing links that were necessary to understand the biogenesis and some of the functions of HDL. Existing data indicate that functional interactions between apoA-I and ABCA1 are necessary for the initial lipidation of apoA-I. Through a series of intermediate steps, lipidated apoA-I proceeds to form discoidal HDL particles that can be converted to spherical particles by the action of lecithin:cholesterol acyltransferase (LCAT). Discoidal and spherical HDL can interact functionally with SR-BI and these interactions lead to selective lipid uptake and net efflux of cholesterol and thus remodel HDL. Defective apoA-I/ABCA1 interactions prevent lipidation of apoA-I that is necessary for the formation of HDL particles. In the same way, specific mutations in apoA-I or LCAT prevent the conversion of discoidal to spherical HDL particles. The interactions of lipid-bound apoA-I with SR-BI are affected in vitro by specific mutations in apoA-I or SR-BI. Furthermore, deficiency of SR-BI affects the lipid and apolipoprotein composition of HDL and is associated with increased susceptibility to atherosclerosis. Here we review the current status of the pathway of HDL biogenesis and mutations in apoA-I, ABCA1, and SR-BI that disrupt different steps of the pathway and may lead to dyslipidemia and atherosclerosis in mouse models. The phenotypes generated in experimental mouse models for apoA-I, ABCA1, LCAT, SR-BI, and other proteins of the HDL pathway may facilitate early diagnosis of similar phenotypes in the human population and provide guidance for proper treatment.
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110 Another study suggested that phosphorylation of Thr-1286 and Thr-1305 within a proline, glutamic acid, serine, and threonine-rich domain (PEST) of ABCA1 promoted the calpain-mediated degradation in differentiated THP-1 cells and that binding of apoA-I to ABCA1 promoted dephos- 509 13 65 67 98 100 120 122 142 144 164 184 219 242166 186 22887 208 12 34 5 6 7 8,91 0 Leu90Pro ∆Lys107 Pr ApoA-I mutations associated with reduced LCAT activation and/or low HDL levels COOHNH2 509 13 65 67 98 100 120 122 142 144 164 184 219 242166 186 22887 208 1 2 3 4 5 6 7 8,9 10 Gly26Arg Trp50Arg Leu60Arg ∆(60-71), INS Val, Thr ∆(70-72) Arg173Pro ∆Lys107 Leu141Arg Pro143Arg ∆Glu235 FS 203-229, ∆(230-243), Arg173Cys ∆(165-175) o165Arg FS 162-207, ∆(208-243) Arg160Leu Leu159Arg Leu159Pro Ala158Glu Val156Glu Arg151Cys ∆(146-160) Leu144Arg ApoA-I mutations associated with reduced LCAT activation and/or low HDL levels ApoA-I mutations associated with familial amyloidosis and low HDL levels b Fig. 2 (continued) phorylation and decreased its degradation [57].
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ABCA1 p.Leu144Arg 16501936:110:876
status: NEW[hide] HDL Cholesterol and Risk of Type 2 Diabetes: A Men... Diabetes. 2015 Sep;64(9):3328-33. doi: 10.2337/db14-1603. Epub 2015 May 13. Haase CL, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R
HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study.
Diabetes. 2015 Sep;64(9):3328-33. doi: 10.2337/db14-1603. Epub 2015 May 13., [PMID:25972569]
Abstract [show]
Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores and allele numbers associated with up to -13 and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2 diabetes for a 0.2 mmol/L reduction in HDL cholesterol were 0.91 (0.75-1.09) and 0.93 (0.78-1.11) for HDL cholesterol-decreasing gene scores and allele numbers, respectively, compared with the corresponding observational hazard ratio of 1.37 (1.32-1.42). In conclusion, genetically reduced HDL cholesterol does not associate with increased risk of type 2 diabetes, suggesting that the corresponding observational association is due to confounding and/or reverse causation.
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36 ATP-binding cassette transporter A1 (ABCA1) N1800H (rs146292819), cholesteryl-ester transfer protein (CETP) 2629C.A (rs1800775) and Taq1bG.A (rs708272), lecithin-cholesterol acyltransferase (LCAT) S208T (rs4986970), hepatic lipase (LIPC) 2480C.T (rs1800588), apolipoprotein A1 (APOA1) S36A (rs199759119), F71Y (rs138407155), K107del (rs number not available), and L144R (rs number not available) were genotyped using an ABI PRISM 7900HT Sequence Detection System (Applied Biosystems, Life Technologies, Paisley, U.K.) and TaqMan-based assays.
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ABCA1 p.Leu144Arg 25972569:36:364
status: NEW