ABCMdb

ABCA1 p.Arg1851*

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Publications

PMID: 22923419 [PubMed] Reddy MV et al: "Exome sequencing identifies 2 rare variants for low high-density lipoprotein cholesterol in an extended family."

No. Sentence Comment

38 Genotype by sex interaction We included the extended family together with 10 additional families with previously identified mutations in ABCA16-8 in a gene-sex interaction analysis, comprising 200 individuals and 9 different mutations in ABCA1 (DelED1893, G616V, K776N, N1800H, Q2210H, R1851X, R2084X, R909X and S1731C). Login to comment
41 Genotype by Sex Interaction We included the extended family together with 10 additional families with previously identified mutations in ABCA16 -8 in a gene-sex interaction analysis, comprising 200 individuals and 9 different mutations in ABCA1 (DelED1893, G616V, K776N, N1800H, Q2210H, R1851X, R2084X, R909X, and S1731C). Login to comment
158 Figure 3 shows the age-sex specific population HDL-C percentiles by ABCA1 genotypes and sex in 200 French-Canadian family members from 11 French-Canadian families with different ABCA1 mutations (DelED1893, G616V, K776N, N1800H, Q2210H, R1851X, R2084X, R909X, and S1731C). Login to comment

PMID: 21575609 [PubMed] Sorrenson B et al: "An ABCA1 truncation shows no dominant negative effect in a familial hypoalphalipoproteinemia pedigree with three ABCA1 mutations."

No. Sentence Comment

20 Expression and functional analysis of truncated ABCA1 mutants in isolation is limited to the ABCA1 p.R1851X truncation [9,10]. Login to comment

PMID: 16343503 [PubMed] Alrasadi K et al: "Functional mutations of the ABCA1 gene in subjects of French-Canadian descent with HDL deficiency."

No. Sentence Comment

6 Three probands had the S1731C mutation, while two others had the R1851X and K776N documented mutations, respectively. Login to comment
86 Table 2 Mutations of the ABCA1 gene in French-Canadian probands with HDL deficiency and defective cellular lipid efflux Probandsa Gene region Nucleotide change Amino acid change Predicted effect by Polyphenb Reference ABE Exon 48 C6370T R2084X Truncated protein [8,9] MGA Exon 14 del 2017-2019 del L693 Probably damaging [8,9] ALA Exon 41 del 5618-5623 del ED1893,4 Probably damaging [8,9] RLA Exon 18 C2665T R909X Truncated protein [8,9] RDU Exon 41 C5864T R1851X Truncated protein [4] SBO Exon 40 A5711C N1800H Possibly damaging [27] Exon 49 G6943C Q2210H Probably damaging - RPH Exon 14 G2160T G616V Probably damaging - GOB Exon 41 del 5833 fs F1840L, L1869X Truncated protein - LNO Exon 38 C5505G S1731C Possibly damaging [4] VDU Exon 38 C5505G S1731C Possibly damaging [4] RRI Exon 38 C5505G S1731C Possibly damaging [4] PCH Exon 16 G2641C K776N Possibly damaging [5] GCH - - - - - LBO - - - - - a Probands refer to subjects ID # 301 in the pedigrees. b Polyphen computer software (http://www.bork.embl-heidelberg.de/polphen/). Login to comment
110 In the remaining eight probands, we identified a previously reported mutation [4], R1851X, in proband RDU that perfectly segregated with the low HDL-C trait in the kindred (Fig. 2A). Login to comment

PMID: 14576201 [PubMed] Hong SH et al: "Novel polypyrimidine variation (IVS46: del T -39...-46) in ABCA1 causes exon skipping and contributes to HDL cholesterol deficiency in a family with premature coronary disease."

No. Sentence Comment

100 between premature CHD and either increased carotid intimal-medial thickness or reduced ABCA1-mediated cholesterol efflux.25-27 The premature CHD identified in the proband extends previous observational data in normolipidemic indi- viduals1-3 and may not only reflect alterations in RCT but other recently identified antiatherogenic effects potentially subserved by HDL including reduced ischemic-reperfusion injury28 and improved vascular function.29 To date, only a small proportion of ABCA1 variants have been characterized in pivotal regions (eg, extracellular loop, transmembrane domain, nucleotide binding folds, C-terminus) that when altered, result in marked reduction in ABCA1 activity and/or function.6,7 The G5947A/ R1851Q mutation occurs within the extracellular loop proximal to the final transmembrane spanner and bears regional similarity to the C5946T/R1851X variant recently reported in a compound heterozygote with TD.30 Variants located within the extracellular loop (between amino acids 1370 to 1650) have been shown to adversely affect the interaction of ABCA1 and ApoA-I resulting in reduced cholesterol efflux.31 Whether distal variants (eg, N1800H, R1851G) exhibit similar interactions with ApoA-I has not been studied, but the marked reductions in HDL-C that have been observed in affected subjects suggest that binding may be similarly disrupted. Login to comment
95 Ho Hong et al Exon Skipping in ABCA1 and HDL-C Deficiency between premature CHD and either increased carotid intimal-medial thickness or reduced ABCA1-mediated cholesterol efflux.25-27 The premature CHD identified in the proband extends previous observational data in normolipidemic indi- viduals1-3 and may not only reflect alterations in RCT but other recently identified antiatherogenic effects potentially subserved by HDL including reduced ischemic-reperfusion injury28 and improved vascular function.29 To date, only a small proportion of ABCA1 variants have been characterized in pivotal regions (eg, extracellular loop, transmembrane domain, nucleotide binding folds, C-terminus) that when altered, result in marked reduction in ABCA1 activity and/or function.6,7 The G5947A/ R1851Q mutation occurs within the extracellular loop proximal to the final transmembrane spanner and bears regional similarity to the C5946T/R1851X variant recently reported in a compound heterozygote with TD.30 Variants located within the extracellular loop (between amino acids 1370 to 1650) have been shown to adversely affect the interaction of ABCA1 and ApoA-I resulting in reduced cholesterol efflux.31 Whether distal variants (eg, N1800H, R1851G) exhibit similar interactions with ApoA-I has not been studied, but the marked reductions in HDL-C that have been observed in affected subjects suggest that binding may be similarly disrupted. Login to comment

PMID: 12840658 [PubMed] Miller M et al: "Genetics of HDL regulation in humans."

No. Sentence Comment

67 TD 3` deletion (intron 38) truncated truncation [61] 5587 C/G 38 S1731C extracellular [68] TD 5793 A/C 40 N1800H extracellular loop, sm [65] FHA 5946 C/T 41 R1851X truncation [75..] FHA 6068 del 42 del 1893-1894(E,D) cytoplasmic [63] TD 6152 (14bp Ins) (42-43) truncated truncation [67] 6316 A/G 44 K1974R cytoplasmic [67] 6421 T/C 45 F2009S cytoplasmic [9] TD 6636 C/T 47 R2081W cytoplasmic [64] FHA 6825 C/T 49 R2144X cytoplasmic [63] TD 6825 del C 49 2145X truncation [62] FHA 6844 C/T 49 P2150L cytoplasmic [62] 6898 C/T 49 P2168L cytoplasmic [67] TD CTC6952-4TT 49 2203X truncation [62] TD 6968 (4bp Ins) 49 2215X, truncated PDZ binding (cyto) [65] *Location in accordance with Santamaria-Fojo et al. (Proc Natl Acad Sci U S A 2000; 97:7987-7992). Login to comment

PMID: 12401893 [PubMed] Wellington CL et al: "Truncation mutations in ABCA1 suppress normal upregulation of full-length ABCA1 by 9-cis-retinoic acid and 22-R-hydroxycholesterol."

No. Sentence Comment

27 One new heterozygous subject is included in this study who is from a new TD kindred ( JP2) and contains the truncation mutation R1851X (13). Login to comment
163 Coexpression of FLAG-tagged ABCA1 truncated at amino acid 1851 (R1851X) significantly inhibited efflux compared with cells transfected with a single copy of wild-type ABCA1 (P Ͻ 0.001, n ϭ 3, Fig. 5B). Login to comment
164 Finally, cells were cotransfected with Xpress-tagged wild-type and FLAG-tagged missense ABCA1 (N1611D). Login to comment
196 Cos-7 cells were transfected singly with vector (mock), Xpress-tagged wild-type human ABCA1 cDNA (WT/Xpress), or cotransfected with FLAG-tagged wild-type ABCA1 (WT/Xpress ϩ WT/FLAG), FLAG-tagged ABCA1 containing the N1611D mutation (WT/Xpress ϩ N1611D/FLAG), or with FLAG-tagged ABCA1 containing the R1851X mutation (WT/Xpress ϩ R1851X/FLAG). Login to comment
197 Cos-7 cells were transfected singly with vector (mock), Xpress-tagged wild-type human ABCA1 cDNA (WT/Xpress), or cotransfected with FLAG-tagged wild-type ABCA1 (WT/Xpress WT/FLAG), FLAG-tagged ABCA1 containing the N1611D mutation (WT/Xpress N1611D/FLAG), or with FLAG-tagged ABCA1 containing the R1851X mutation (WT/Xpress R1851X/FLAG). Login to comment

PMID: 12176027 [PubMed] Ohama T et al: "Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands."

No. Sentence Comment

40 In these control experiments, we used the fibroblasts from a homozygous patient with Tangier disease carrying R1851X mutation [10] lacking the epitope for Ab ABCA12177 as a negative control. Login to comment

PMID: 11785958 [PubMed] Nishida Y et al: "Expression and functional analyses of novel mutations of ATP-binding cassette transporter-1 in Japanese patients with high-density lipoprotein deficiency."

No. Sentence Comment

1 In order to know the molecular basis for FHD, we characterized three different ABCA1 mutations associated with FHD (G1158A/ A255T, C5946T/R1851X, and A5226G/N1611D) with respect to their expression in the passaged fibroblasts from the patients and in the cells transfected with the mutated cDNAs. Login to comment
3 In the fibroblasts homozygous for C5946T/R1851X, ABCA1 mRNA was comparable. Login to comment
4 Because the mutant ABCA1 protein (R1851X) was predicted to lack the epitope for the antibody used, we transfected FLAG-tagged truncated mutant (R1851X/ABCA1-FLAG) cDNA into Cos-7 cells, showing that the mutant protein expression was markedly reduced. Login to comment
59 TABLE 1 Clinical Profiles of Patients with Familial HDL Deficiency Case 1 Case 2 Case 3 ABCA1 substitutions found (nt/aa) G1158A/A255T C5946T/R1851X A5226G/N1611D Age (years)/sex (M, F) 56/M 71/F 53/F Total cholesterol (mmol/L) 0.72 1.47 2.7 HDL-cholesterol (mmol/L) 0.16 0.05 0.11 Triglyceride (mmol/L) 2.6 3.27 1.75 Apo-Al (mg/dL) 3.9 5.0 11.0 Atherosclerosis ϩ ϩ ϩ Typical TD phenotype ϩ ϩ - Cholesterol efflux (% of control) 5.0 2.0 7.0 Note. Login to comment
105 R1851X appeared to lack the second nucleotide binding domain. Login to comment
109 We could not find the G1158A/A255T substitution in 48 unrelated Americans or 176 Japanese control subjects (data not shown). Login to comment
111 This mutation caused a premature stop at the codon 1851 (R1851X), resulting that the predicted ABCA1 protein was truncated from lacking the second nucleotide binding domain (NBD) (Figs. 1B and 2). Login to comment
116 In Cases 2 (Ho/ R1851X) and 3 (Ho/N1611D), the expression of mRNA did not appear to be altered with and without the stimulation (Figs. 3A and 3B). Login to comment
120 As it was noted that the predicted mutant ABCA1 (R1851X) lacked the epitope for the antibody we used, we could not see any immunoreactive mass in fibroblasts from Case 2 (Ho/ R1851X). Login to comment
125 It was striking that the protein expression of cDNA construct carrying the truncated mutation (R1851X) was extremely low, though we could see the expected band with smaller size. Login to comment
130 As expected, no significant cholesterol efflux could be detected from cells transfected with R1851X/ ABCA1-FLAG cDNA. Login to comment
145 In Case 2, we found another novel mutation resulting in the presence of truncated ABCA1 which lacks the second NBD (R1851X). Login to comment
146 Our transfection study demonstrated an interesting data to show that the expression level of truncated mutant (R1851X) was much lower than those of other mutants and wild type tested. Login to comment
151 Based upon the results of our transfection experiment (Fig. 3), we speculated that ABCA1 expression was severely impaired at the protein level in Case 2 (Ho/R1851X). Login to comment
58 TABLE 1 Clinical Profiles of Patients with Familial HDL Deficiency Case 1 Case 2 Case 3 ABCA1 substitutions found (nt/aa) G1158A/A255T C5946T/R1851X A5226G/N1611D Age (years)/sex (M, F) 56/M 71/F 53/F Total cholesterol (mmol/L) 0.72 1.47 2.7 HDL-cholesterol (mmol/L) 0.16 0.05 0.11 Triglyceride (mmol/L) 2.6 3.27 1.75 Apo-Al (mg/dL) 3.9 5.0 11.0 Atherosclerosis af9; af9; af9; Typical TD phenotype af9; af9; afa; Cholesterol efflux (% of control) 5.0 2.0 7.0 Note. Login to comment
104 R1851X appeared to lack the second nucleotide binding domain. Login to comment
114 In Cases 2 (Ho/ R1851X) and 3 (Ho/N1611D), the expression of mRNA did not appear to be altered with and without the stimulation (Figs. 3A and 3B). Login to comment
118 As it was noted that the predicted mutant ABCA1 (R1851X) lacked the epitope for the antibody we used, we could not see any immunoreactive mass in fibroblasts from Case 2 (Ho/ R1851X). Login to comment
123 It was striking that the protein expression of cDNA construct carrying the truncated mutation (R1851X) was extremely low, though we could see the expected band with smaller size. Login to comment
128 As expected, no significant cholesterol efflux could be detected from cells transfected with R1851X/ ABCA1-FLAG cDNA. Login to comment
143 In Case 2, we found another novel mutation resulting in the presence of truncated ABCA1 which lacks the second NBD (R1851X). Login to comment
144 Our transfection study demonstrated an interesting data to show that the expression level of truncated mutant (R1851X) was much lower than those of other mutants and wild type tested. Login to comment
149 Based upon the results of our transfection experiment (Fig. 3), we speculated that ABCA1 expression was severely impaired at the protein level in Case 2 (Ho/R1851X). Login to comment