ABCA1 p.Arg130Lys
| Predicted by SNAP2: | A: N (82%), C: N (53%), D: D (53%), E: N (66%), F: D (71%), G: N (57%), H: N (82%), I: N (78%), K: N (93%), L: N (61%), M: N (78%), N: N (66%), P: N (61%), Q: N (72%), S: N (82%), T: N (78%), V: N (57%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, S: N, T: N, V: N, W: D, Y: N, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Novel mutations of ABCA1 transporter in patients w... Mol Genet Metab. 2012 Nov;107(3):534-41. doi: 10.1016/j.ymgme.2012.08.005. Epub 2012 Aug 18. Fasano T, Zanoni P, Rabacchi C, Pisciotta L, Favari E, Adorni MP, Deegan PB, Park A, Hlaing T, Feher MD, Jones B, Uzak AS, Kardas F, Dardis A, Sechi A, Bembi B, Minuz P, Bertolini S, Bernini F, Calandra S
Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency.
Mol Genet Metab. 2012 Nov;107(3):534-41. doi: 10.1016/j.ymgme.2012.08.005. Epub 2012 Aug 18., [PMID:22959828]
Abstract [show]
The objective of the study was the characterization of ABCA1 gene mutations in 10 patients with extremely low HDL-cholesterol. Five patients (aged 6 months to 76 years) presented with splenomegaly and thrombocytopenia suggesting the diagnosis of Tangier disease (TD). Three of them were homozygous for novel mutations either in intron (c.4465-34A>G) or in exons (c.4376delT and c.5449C>T), predicted to encode truncated proteins. One patient was compound heterozygous for a nucleotide insertion (c.1758_1759insG), resulting in a truncated protein and for a nucleotide substitution c.4799A>G, resulting in a missense mutation (p.H1600R). The last TD patient, found to be heterozygous for a known mutation (p.D1009Y), had a complete defect in ABCA1-mediated cholesterol efflux in fibroblasts, suggesting the presence of a second undetected mutant allele. Among the other patients, four were asymptomatic, but one, with multiple risk factors, had severe peripheral artery disease. Three of these patients were heterozygous for known mutations (p.R130K+p.N1800H, p.R1068C, p.N1800H), while two were carriers of novel mutations (c.1195-27G>A and c.396_397insA), predicted to encode truncated proteins. The pathogenic effect of the two intronic mutations (c. 1195-27G>A and c.4465-34A>G) was demonstrated by the analysis of the transcripts of splicing reporter mutant minigenes expressed in COS-1 cells. Both mutations activated an intronic acceptor splice site which resulted in a partial intron retention in mature mRNA with the production of truncated proteins. This study confirms the allelic heterogeneity of TD and suggests that the diagnosis of TD must be considered in patients with an unexplained splenomegaly, associated with thrombocytopenia and hypocholesterolemia.
Comments [show]
None has been submitted yet.
No. Sentence Comment
134 Mo-2 33y (M) TD 2.8 1.2 3.2 0.14 na b0.3 [c.1758_1759insG], p.R587Afs*43+[c.4799A>G], p.H1600R Mo-3 6y (F) TD 1.6 0.9 1.5 0.06 na nd [c.4465-34A>G,ins-33_-1]+[c.4465-34A>G,ins-33_-1], p.Q1488_1489insRPVCLVFM*9 Mo-4 32y (M) TD 1.3 na 2.1 0.03 0.4 b0.3 [c.4367delT]+[c.4367delT], p.M1456Sfs*45 Mo-5 6m (M) TD 2.5 0.57 1.5 0.13 na na [c.5449C>T]+[c.5449C>T], p.R1817* Mo-6 69y (F) FHD 3.7 2.7 1.5 0.3 0.97 0.4 [c.389G>A; c.5398A>C], p.R130K; p.N1800H+[wild type] Mo-7 37y (M) FHD 4.3 na 13.4 0.14 1.29 b0.3 [c.1195-27G>A,ins-25_-1], p.E398ins8V399Gfs*13+[wild type] Geߚ8 60y (F) FHD 5.6 3.6 3.5 0.72 1.16 1.0 [c.396_397insA], p.Q133Tfs*20+[wild type] Ge-9 54y (M) FHD 5.8 3.3 4.4 0.57 1.28 0.8 [c.3202C>T], p.R1068C+[wild type] Ge-10 52y (M) FHD 5.9 4.0 3.7 0.49 0.78 1.37 [c.5398A>C], p.N1800H+[wild type] TD = Tangier disease; FHD = familial HDL deficiency; y = years; m = months; M = males; F = females; na = not available, nd = not detectable.
X
ABCA1 p.Arg130Lys 22959828:134:432
status: NEW176 PolyPhen (PSIC score) SIFT (P score) p.R130K Possibly damaging (1.540) Predicted tolerated p.R1068C Probably damaging (3.143) Predicted not tolerated (0.00) p.D1099Y Probably damaging (3.047) Predicted not tolerated (0.00) p.H1600R Probably damaging (3.197) Predicted not tolerated (0.02) p.N1800H Possibly damaging (1.845) Predicted tolerated termination codon (p.R587Afs*43) and ii) a single nucleotide substitution (c.4799A>G) in exon 36, resulting in a novel missense mutation (p.H1600R) (Table 1).
X
ABCA1 p.Arg130Lys 22959828:176:39
status: NEW193 3.6. Patient # Mo-6 3.6.1. Analysis of ABCA1 gene This patient was a carrier of two single nucleotide substitutions: i) c.389G>A resulting in the conversion of arginine to lysine (p.R130K) predicted in silico to be benign and ii) c.5398A>C resulting in a previously reported missense mutation (p.N1800H) [8], predicted in silico to be possibly damaging (Table 2).
X
ABCA1 p.Arg130Lys 22959828:193:182
status: NEW