ABCA1 p.Val1704Asp

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PMID: 18974039 [PubMed] Juan T et al: "Identification of three loci affecting HDL-cholesterol levels in a screen for chemically induced recessive mutations in mice."
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246 The S1748L mutation is predicted to be located in a transmembrane domain between the V1704D and N1800H missense mutations identified in patients with Tangier disease (39).
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ABCA1 p.Val1704Asp 18974039:246:85
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247 Although 44 missense mutations have been identified in ABCA1, only 2 (W840R and V1704D) are expected to lie in the transmembrane domain.
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ABCA1 p.Val1704Asp 18974039:247:80
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248 Although 44 missense mutations have been identified in ABCA1, only 2 (W840R and V1704D) are expected to lie in the transmembrane domain.
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ABCA1 p.Val1704Asp 18974039:248:80
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PMID: 17412755 [PubMed] Kyriakou T et al: "Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients."
No. Sentence Comment
67 As expected, compared with the rate of cholesterol efflux in cells transfected with the plasmid expressing the wild-type ABCA1, the rates of cholesterol efflux were significantly lower in untransfected cells and in cells transfected with the plasmid expressing the ABCA1 (V1704D and L1379F) mutant which had previously been shown to result in complete loss of ABCA1 function (24) (P , 0.001; Fig. 4).
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ABCA1 p.Val1704Asp 17412755:67:272
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146 Cultured COS-7 cells were transfected with each of the above plasmids or a plasmid expressing an ABCA1 mutant (V1704D and L1379F) described in Albrecht et al. (24).
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ABCA1 p.Val1704Asp 17412755:146:111
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172 K.O. refers to an ABCA1 (V1704D and L1379F) mutant which had previously been shown to result in complete loss of ABCA1 function (24).
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ABCA1 p.Val1704Asp 17412755:172:25
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69 As expected, compared with the rate of cholesterol efflux in cells transfected with the plasmid expressing the wild-type ABCA1, the rates of cholesterol efflux were significantly lower in untransfected cells and in cells transfected with the plasmid expressing the ABCA1 (V1704D and L1379F) mutant which had previously been shown to result in complete loss of ABCA1 function (24) (P , 0.001; Fig. 4).
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ABCA1 p.Val1704Asp 17412755:69:272
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145 Cultured COS-7 cells were transfected with each of the above plasmids or a plasmid expressing an ABCA1 mutant (V1704D and L1379F) described in Albrecht et al. (24).
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ABCA1 p.Val1704Asp 17412755:145:111
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171 K.O. refers to an ABCA1 (V1704D and L1379F) mutant which had previously been shown to result in complete loss of ABCA1 function (24).
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ABCA1 p.Val1704Asp 17412755:171:25
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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
48 This SNP has been reported to be associated with decreased HDL cholesterol and increased severity of atherosclerosis in Table 1. subPSEC Scores and Probability of Functional Impairment (Pdeleterious) for ABCA1 Mutations and SNPs Mutations SNPs Variant SubPSEC Pdeleterious Variant subPSEC Pdeleterious P85L À4.62 0.83 R219K À0.57 0.08 H160F À2.79 0.45 V399A À2.26 0.32 R230C À4.27 0.78 V771M À2.86 0.46 A255T À1.81 0.23 T774P À1.99 0.27 E284K À2.34 0.34 K776N À3.53 0.63 Y482C À4.21 0.77 V825I À1.06 0.13 R587W À6.04 0.95 I883M À1.38 0.17 W590S À5.19 0.9 E1172D À1.96 0.26 W590L À4.48 0.82 R1587K À0.58 0.08 Q597R À7.15 0.98 S1731C À4.21 0.77 T929I À4.29 0.78 N935H À8.54 1 N935S À7.53 0.99 A937V À6.6 0.97 A1046D À7.52 0.99 M1091T À3.56 0.64 D1099Y À6.09 0.96 D1289N À2.48 0.37 L1379F À3.81 0.69 C1477R À5.44 0.92 S1506L À5.17 0.9 N1611D À5.69 0.94 R1680W À6.02 0.95 V1704D À3.21 0.55 N1800H À4.23 0.77 R1901S À5.06 0.89 F2009S À2.73 0.43 R2081W À8.08 0.99 P2150L À2.88 0.47 Q2196H À2.74 0.43 DOI: 10.1371/journal.pgen.0010083.t001 PLoS Genetics | www.plosgenetics.org December 2005 | Volume 1 | Issue 6 | e83 0740 Accurate Prediction of ABCA1 Variants Synopsis A major goal of human genetics research is to understand how genetic variation leads to differences in the function of genes.
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ABCA1 p.Val1704Asp 16429166:48:868
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ABCA1 p.Val1704Asp 16429166:48:1033
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PMID: 15158913 [PubMed] Albrecht C et al: "Two novel missense mutations in ABCA1 result in altered trafficking and cause severe autosomal recessive HDL deficiency."
No. Sentence Comment
3 ApoAI-mediated efflux of cholesterol from the proband`s fibroblasts was less than 10% of normal and nucleotide sequencing revealed inheritance of two novel mutations in ABCAI, V1704D and L1379F.
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ABCA1 p.Val1704Asp 15158913:3:176
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6 Severe HDL deficiency in the proband was caused by two novel autosomal recessive mutations in ABCA1, one (V1704D) predicted to lie in a transmembrane segment and the other (L1379F) in a large extracellular loop.
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ABCA1 p.Val1704Asp 15158913:6:106
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23 In this study, we describe a patient who has inherited two defective alleles of ABCA1 from apparently unaffected parents, each encoding a previously undescribed single amino acid substitution (L1379F and V1704D).
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ABCA1 p.Val1704Asp 15158913:23:204
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116 In the proband, the paternal allele (clear box) carried the L1379F variant of ABCA1, and the maternal allele (shaded box) carried the V1704D variant.
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ABCA1 p.Val1704Asp 15158913:116:134
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150 In comparison, the allele frequency of the R219K polymorphism was 0.22 (K allele), similar to that found in other European populations [31].
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ABCA1 p.Val1704Asp 15158913:150:84
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151 The proband`s father was heterozygous for L1379F, and her mother and sister for the V1704D variant (Fig. 1).
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ABCA1 p.Val1704Asp 15158913:151:84
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153 Expression of normal and mutant ABCA1 in vitro The L1379F and V1704D mutations were introduced into the full-length cDNA for ABCA1, fused at its carboxy-terminus to eGFP.
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ABCA1 p.Val1704Asp 15158913:153:62
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157 (a) Confocal sections of transiently transfected HEK 293 cells expressing wild-type ABCA1-eGFP (left panel), ABCA1-eGFP L1379F (middle panel) and ABCA1-eGFP V1704D (right panel); eGFP fluorescence is shown in green and DAPI staining of nuclear DNA in blue.
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ABCA1 p.Val1704Asp 15158913:157:157
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159 (b) HEK 293 cells expressing wild-type ABCA1-eGFP, ABCA1-eGFP L1379F and ABCA1-eGFP V1704D were stained for SERCA 2 as an ER marker.
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ABCA1 p.Val1704Asp 15158913:159:84
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161 A large extent of co-localisation was found for both mutants, suggesting retention of L1379F and V1704D in the ER.
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ABCA1 p.Val1704Asp 15158913:161:97
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175 Discussion We describe a patient of English origin with severe HDL deficiency and premature coronary disease who is heterozygous for two rare alleles of ABCA1 that are predicted to cause single amino acid substitutions, L1379F and V1704D.
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ABCA1 p.Val1704Asp 15158913:175:231
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206 The position of the L1379F substitution in ABCA1 is indicated in bold; the residues predicted by Simple Modular Architecture Research Tool (SMART; http://www.smart.embl-heidelberg.de) analysis of the amino acid sequence of ABCA1 to form membrane-spanning segment 7 in ABCA1 and ABCA4 are underlined.
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ABCA1 p.Val1704Asp 15158913:206:124
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207 (b) Above, alignment of human, mouse and chicken ABCA1 and below, human ABCA1 with human ABCA4, showing the position of the V1704D mutation in ABCA1 (indicated in bold).
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ABCA1 p.Val1704Asp 15158913:207:124
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115 In the proband, the paternal allele (clear box) carried the L1379F variant of ABCA1, and the maternal allele (shaded box) carried the V1704D variant.
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ABCA1 p.Val1704Asp 15158913:115:134
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152 Expression of normal and mutant ABCA1 in vitro The L1379F and V1704D mutations were introduced into the full-length cDNA for ABCA1, fused at its carboxyterminus to eGFP.
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ABCA1 p.Val1704Asp 15158913:152:62
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156 (a) Confocal sections of transiently transfected HEK 293 cells expressing wild-type ABCA1-eGFP (left panel), ABCA1-eGFP L1379F (middle panel) and ABCA1-eGFP V1704D (right panel); eGFP fluorescence is shown in green and DAPI staining of nuclear DNA in blue.
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ABCA1 p.Val1704Asp 15158913:156:157
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158 (b) HEK 293 cells expressing wild-type ABCA1-eGFP, ABCA1-eGFP L1379F and ABCA1-eGFP V1704D were stained for SERCA 2 as an ER marker.
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ABCA1 p.Val1704Asp 15158913:158:84
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160 A large extent of co-localisation was found for both mutants, suggesting retention of L1379F and V1704D in the ER.
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ABCA1 p.Val1704Asp 15158913:160:97
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174 Discussion We describe a patient of English origin with severe HDL deficiency and premature coronary disease who is heterozygous for two rare alleles of ABCA1 that are predicted to cause single amino acid substitutions, L1379F and V1704D.
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ABCA1 p.Val1704Asp 15158913:174:231
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PMID: 26546829 [PubMed] Ramasamy I et al: "Update on the molecular biology of dyslipidemias."
No. Sentence Comment
1056 Severe HDL deficiency in a patient was caused by two autosomal recessive mutations of ABCA1, one predicted to lie in the transmembrane segment (V1704D) and the other (L1379F) in the extracellular loop.
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ABCA1 p.Val1704Asp 26546829:1056:144
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