ABCA1 p.Ser107Tyr
| Predicted by SNAP2: | A: N (93%), C: N (82%), D: N (87%), E: N (93%), F: N (66%), G: N (87%), H: N (82%), I: N (87%), K: N (93%), L: N (87%), M: N (78%), N: N (93%), P: N (72%), Q: N (93%), R: N (93%), T: N (97%), V: N (87%), W: N (57%), Y: N (72%), |
| Predicted by PROVEAN: | A: N, 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, T: N, V: N, W: D, Y: N, |
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[hide] Genetic etiology of isolated low HDL syndrome: inc... Arterioscler Thromb Vasc Biol. 2007 May;27(5):1139-45. Epub 2007 Feb 15. Kiss RS, Kavaslar N, Okuhira K, Freeman MW, Walter S, Milne RW, McPherson R, Marcel YL
Genetic etiology of isolated low HDL syndrome: incidence and heterogeneity of efflux defects.
Arterioscler Thromb Vasc Biol. 2007 May;27(5):1139-45. Epub 2007 Feb 15., [PMID:17303779]
Abstract [show]
OBJECTIVE: We have used a multitiered approach to identify genetic and cellular contributors to high-density lipoprotein (HDL) deficiency in 124 human subjects. METHODS AND RESULTS: We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 2 in apolipoprotein A-I (APOA1), 4 in lecithin:cholesterol acyltransferase (LCAT), 1 in phospholipid transfer protein (PLTP), and 7 in the ATP-binding cassette transporter ABCA1, leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. Cholesterol efflux assays performed using cholesterol-loaded monocyte-derived macrophages from the 124 low HDL subjects and 48 control subjects revealed that 33% (41/124) of low HDL subjects had low efflux, despite the fact that the majority of these subjects (34/41) were not carriers of dysfunctional ABCA1 alleles. In contrast, only 2% of control subjects presented with low efflux (1/48). In 3 families without ABCA1 mutations, efflux defects were found to cosegregate with low HDL. CONCLUSIONS: Efflux defects are frequent in low HDL syndromes, but the majority of HDL deficient subjects with cellular cholesterol efflux defects do not harbor ABCA1 mutations, suggesting that novel pathways contribute to this phenotype.
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No. Sentence Comment
43 In the coding region of PLTP, 2 heterozygous nonsynonymous sequence variants were detected in the low HDL population: S107Y and R459Q.
X
ABCA1 p.Ser107Tyr 17303779:43:118
status: NEW45 Previous studies demonstrated the importance of the C-terminal region for the functional activity of PLTP and the arginine at position 459 is within the C-terminus.31 PLTP expression in COS7 cells showed that PLTP mutants S107Y and R459Q had normal and 33% decrease in specific activity relative to wild-type protein, respectively (115.3Ϯ11.2, 66.7Ϯ6.0 of wild-type activity).
X
ABCA1 p.Ser107Tyr 17303779:45:222
status: NEW46 These results suggest that S107Y mutant has normal function, but the R459Q mutant had a significant reduction in activity, which could contribute to impaired HDL metabolism.
X
ABCA1 p.Ser107Tyr 17303779:46:27
status: NEW38 In the coding region of PLTP, 2 heterozygous nonsynonymous sequence variants were detected in the low HDL population: S107Y and R459Q.
X
ABCA1 p.Ser107Tyr 17303779:38:118
status: NEW40 Previous studies demonstrated the importance of the C-terminal region for the functional activity of PLTP and the arginine at position 459 is within the C-terminus.31 PLTP expression in COS7 cells showed that PLTP mutants S107Y and R459Q had normal and 33% decrease in specific activity relative to wild-type protein, respectively (115.3afe;11.2, 66.7afe;6.0 of wild-type activity).
X
ABCA1 p.Ser107Tyr 17303779:40:222
status: NEW41 These results suggest that S107Y mutant has normal function, but the R459Q mutant had a significant reduction in activity, which could contribute to impaired HDL metabolism.
X
ABCA1 p.Ser107Tyr 17303779:41:27
status: NEW