ABCMdb

ABCA1 p.Trp590Leu

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Publications

PMID: 17303779 [PubMed] Kiss RS et al: "Genetic etiology of isolated low HDL syndrome: incidence and heterogeneity of efflux defects."

No. Sentence Comment

47 In ABCA1, a total of 19 nonsynonymous coding sequence variants; some of these we reported previously.22 Of these, 9 sequence variants were common polymorphisms (ie, reported in the literature as common or of similar prevalence in control subjects): P85L, P85A, R219K, V399A, V771M, V825I, I883M, E1172D, R1587K.14,32-35 Another 5 sequence variants, identified here, were previously reported to be disease causing: W590L (reported as W590S)14; C1477F (reported as C1477R)13; S1731C (only found in French-Canadian populations)36; N1800H32; and 1851X.37 Five sequence variants were novel: K199F, H551D, R965C, E1386Q, and D1706N. Login to comment
49 Eight subjects with sequence variants in ABCA1 had defective cholesterol efflux (measured in repeated assays cholesterol-loaded monocyte-derived macrophage [MDMs]), and these ABCA1 sequence variants were tested in an in vitro expression system for cholesterol efflux activity.38 ABCA1 proteins containing the sequence variants W590L, C1477F, D1706N, S1731C, or N1800H were all found to have significantly impaired cholesterol efflux, whereas the H551D and E1386Q variants had very minor, if any, effects on cholesterol transport (Figure 1A). Login to comment
88 of Subjects Functional Mutations (All Heterozygous) Percentage of Total Population ApoA-I 2 33X, ⌬K182 2 ABCA1 7 H551D, W590L, C1477F, D1706N, S1731C, N1800H, 1851X 6 LCAT 4 W61X, G104S, N131D, S208T 3 PLTP 1 R459Q 1 Unknown 88 Total no. Login to comment
42 In ABCA1, a total of 19 nonsynonymous coding sequence variants; some of these we reported previously.22 Of these, 9 sequence variants were common polymorphisms (ie, reported in the literature as common or of similar prevalence in control subjects): P85L, P85A, R219K, V399A, V771M, V825I, I883M, E1172D, R1587K.14,32-35 Another 5 sequence variants, identified here, were previously reported to be disease causing: W590L (reported as W590S)14; C1477F (reported as C1477R)13; S1731C (only found in French-Canadian populations)36; N1800H32; and 1851X.37 Five sequence variants were novel: K199F, H551D, R965C, E1386Q, and D1706N. Login to comment
44 Eight subjects with sequence variants in ABCA1 had defective cholesterol efflux (measured in repeated assays cholesterol-loaded monocyte-derived macrophage [MDMs]), and these ABCA1 sequence variants were tested in an in vitro expression system for cholesterol efflux activity.38 ABCA1 proteins containing the sequence variants W590L, C1477F, D1706N, S1731C, or N1800H were all found to have significantly impaired cholesterol efflux, whereas the H551D and E1386Q variants had very minor, if any, effects on cholesterol transport (Figure 1A). Login to comment
83 of Subjects Functional Mutations (All Heterozygous) Percentage of Total Population ApoA-I 2 33X, èc;K182 2 ABCA1 7 H551D, W590L, C1477F, D1706N, S1731C, N1800H, 1851X 6 LCAT 4 W61X, G104S, N131D, S208T 3 PLTP 1 R459Q 1 Unknown 88 Total no. Login to comment

PMID: 17113061 [PubMed] Miller M et al: "Do mutations causing low HDL-C promote increased carotid intima-media thickness?"

No. Sentence Comment

37 These data extend previous observations where increased cIMT was not associated with the ABCA1 variant, W590L [14]. Login to comment

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. Login to comment
110 DOI: 10.1371/journal.pgen.0010083.g003 Table 3. subPSEC Scores for ABCA1 Variants Described in a Cohort of Individuals with Low HDL Cholesterol from the General Population Variant subPSEC Score Macrophage Efflux PolyPhen D1706N À6.57 0.38a Possibly damaging C1477F À5.55 0.34a Probably damaging W590S À5.19 - Probably damaging H551D À4.99 0.32a Probably damaging P85L À4.62 0.8 Probably damaging W590L À4.48 0.31a Probably damaging N1800H À4.23 0.27a Possibly damaging R965C À4.22 0.59 Probably damaging S1731C À4.21 0.28a Possibly damaging A1670T À4.2 - Possibly damaging K401Q À4.2 - Benign T459P À4.11 0.28a Possibly damaging R638Q À4.08 - Possibly damaging L1026P À3.86 0.25a Benign T2073A À3.84 0.28a Possibly damaging E815G À3.53 - Probably damaging R1615Q À3.45 - Possibly damaging S1181F À3.44 - Possibly damaging R306H À3.31 - Benign E1386Q À2.44 0.51 Benign S1376G À2.19 - Benign R1341T À2.09 - Possibly damaging D2243E À1.6 - Benign P248A À0.18 - Benign a Efflux value is 2 SDs or more below control levels of 0.52 6 0.07. Login to comment

PMID: 15767853 [PubMed] Hovingh GK et al: "Inherited disorders of HDL metabolism and atherosclerosis."

No. Sentence Comment

82 In contrast, no effects on carotid IMT were observed in carriers of another ABCA1 mutation (W590L) [37]. Login to comment
85 In addition, HDL-c levels were below 1.0 mmol/l in three of the five ABCA1 mutation carriers and in two of the 10 noncarriers, indicating that the W590L mutation suffers from low penetrance. Login to comment

PMID: 15262183 [PubMed] Probst MC et al: "Screening for functional sequence variations and mutations in ABCA1."

No. Sentence Comment

10 In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). Login to comment
123 These Table 1 Primers and probes for TaqMan analysis of novel polymorphisms in the coding region of ABCA1 W590L (G2082C) TM-W590L-f 5 -AGC TGA CCC CTT TGA GGA CAT-3 TM-W590L-r 5 -CTC CAC CAC ATC CTG CAA GTA G-3 TM-W590-vic 5 -VIC-CCC CCC ¯ AGA CGT A-MGB-NFQ-3 TM-L590-fam 5 -FAM-CCC CCG ¯ AGA CGT A-MGB-NFQ-3 V771M (G2624A) TM-V771M-f 5 -GGC ATC ATC TAC TTC ACG CTG TA-3 TM-V771M-r 5 -CAG AGG TAC TCA CAG CGA AGA TCT T-3 TM-V771-vic 5 -FAM-TGT GAA GCC CAC ¯ GTA G-MGB-NFQ-3 TM-M771-fam 5 -VIC-TGA AGC CCA T ¯ GT AGT C-MGB-NFQ-3 W840R (T2831A) TM-W840R-f 5 -GCT GTT TGA CAC CTT CCT CTA TGG-3 TM-W840R-r 5 -TGT ACC TGG AAA GAC AGC CTC AA-3 TM-W840-vic 5 -VIC-TGT ACC A ¯ GG TCA TCA C-MGB-NFQ-3 TM-R840-fam 5 -FAM-TGT ACC T ¯ GG TCA TCA C-MGB-NFQ-3 P2150L (C6762T) TM-P2150L-f 5 -TTC AGG TTT GGA GAT GGT TAT ACA ATA G-3 TM-P2150L-r 5 -GAA ATG CAA GTC CAA AGA AAT CCT-3 TM-P2150-vic 5 -VIC-CAA CCC ¯ GGA CCT GA-MGB-NFQ-3 TM-L2150-fam 5 -FAM-CAA CCT ¯ GGA CCT GAA-MGB-NFQ-3 F2163S (T6801C) TM-F2163S-f 5 -AAG CCT GTC CAG GAT TTC TTT G-3 TM-F2163S-r 5 -CAT GTT CCG GTG TTT CTC TTT TAG-3 TM-F2163-vic 5 -VIC-CCA GGA A ¯ AT GCA AGT C-MGB-NFQ-3 TM-S2163-fam 5 -FAM-CAG GAG ¯ ATG CAA GTC-MGB-NFQ-3 V2244I (G7043A) TM-V2244I-f 5 -ATG ATG ACC ACT TAA AAG ACC TCT CA-3 TM-V2244I-r 5 -GCT TTC TTT CAC TTT CTC ATC CTG TAG-3 TM-V2244-vic 5 -VIC-TGG ACG ¯ TTG CAG TTC-MGB-NFQ-3 TM-I2244-fam 5 -FAM-AGT AGT GGA CA ¯ T TGC-MGB-NFQ-3 Positions of sequence variations refer to accession number NM005502. Login to comment
186 In the 61-year-old male (patient C), we found the novel mutation G98481T in a heterozygous state, which results in amino acid exchange W590L. Login to comment
192 In addition, patient D was heterozygous for a novel sequence variation in exon 22, Table 5 Sequence variations found in ABCA1 and phenotypes of patients Exon Amino acid Nucleotide Position in DNA (AF275948) Position in mRNA (NM005502) Found in patient with 14 W590L TG ¯ G → TC ¯ G 98481 2082 HDL deficiency (C) 16 V771M G ¯ TG → A ¯ TG 102555 2624 Increased HDL (A) 17 W840R T ¯ GG → A ¯ GG 103822 2831 HDL deficiency (B) 22 R1068C C ¯ GC → T ¯ GC 109904 3515 HDL deficiency (D) 49 F2163S TT ¯ T → TC ¯ T 143483 6801 Low HDL and G6PD deficiency (E) 50 V2244I G ¯ TT → A ¯ TT 144665 7043 A C ABC B S A N ABC B S 44 23 703 681 718 740 769 747 774-794 822 842 1368 1346 1655 1677 1724 1702 1737 1759 1790 1768 1848 1870 642 660 W590L R1068C F2163S P2150L V2244I V771M W840R Fig. 4. Login to comment
241 In the probands with HDL deficiency (patients B, C and D), we have identified three novel sequence variations: W840R, W590L and R1068C. Login to comment
244 It can also be assumed that amino acid exchange W590L, found in patient C, is a mutation causing a defect ABCA1 protein product. Login to comment
245 This is supported by the fact that a mutation in the same codon was shown to cause Tangier disease (W590S) [7], but since the patient is only heterozygous for W590L, it remains unclear what additional mutation in ABCA1 causes the patients analphalipoproteinemia. Login to comment

PMID: 12407001 [PubMed] Hong SH et al: "Lack of association between increased carotid intima-media thickening and decreased HDL-cholesterol in a family with a novel ABCA1 variant, G2265T."

No. Sentence Comment

51 The affected individuals in the kindred were heterozygous for a G2265T substitution (Fig. 2, arrow) with predicted conversion of Trp to Leu (W590L). Login to comment
55 Pedigree of a kindred showing HDL-C segregation of W590L mutation. Login to comment
62 Significant differences between (ϩ) and (-) individuals for the W590L mutation were noted for HDL-C (P ϭ 0.009) and apoA-I (P ϭ 0.036). Login to comment
75 Individuala Sex Age, years TC,b mmol/L TG, mmol/L HDL-C, mmol/L LDL-C, mmol/L apoA-I, g/L apoB, g/L I-2 (-) F 88 5.43 3.28 1.40 3.39 1.67 1.10 I-3 (؉) M 81 4.63 2.20 1.06 3.13 1.21 0.95 II-1 (-) M 48 4.88 4.34 1.14 2.87 1.32 1.00 II-2 (-) F 47 5.53 3.54 1.65 3.18 2.00 1.11 II-3 (؉) M 52 3.10 2.97 0.34 2.17 0.49 0.93 II-4 (-) F 54 3.95 1.63 1.65 1.96 1.54 0.60 II-5 (؉) M 57 5.19 2.38 1.14 3.59 1.39 1.18 II-6 (-) F 54 3.67 1.24 1.14 2.17 1.18 0.64 II-7 (-) M 54 7.13 4.91 1.94 4.21 2.05 1.26 II-8 (؉) F 40 3.80 2.45 0.88 2.43 1.06 0.86 III-1 (-) F 19 4.16 2.48 0.96 2.71 1.01 0.79 III-2 (-) M 27 3.10 2.43 1.27 1.34 1.51 0.54 III-3 (؉) M 31 3.70 2.74 0.54 2.61 0.85 0.98 III-4 (؉) F 28 3.80 2.35 1.03 2.30 1.29 0.80 III-5 (-) F 33 3.98 1.52 1.40 2.27 1.34 0.68 III-6 (-) F 19 3.95 2.74 0.96 2.45 1.10 0.75 III-7 (-) F 27 5.37 2.07 1.96 2.89 1.90 0.93 III-8 (-) M 10 3.64 2.25 1.01 2.20 1.15 0.77 III-9 (-) M 13 3.70 1.60 1.24 2.14 1.24 0.68 III-10 (-) F 17 3.23 3.75 0.88 1.60 1.09 0.62 Mean Ϯ SD (ϩ), n ϭ 6 41.60 Ϯ 12.70 4.04 Ϯ 0.75 2.52 Ϯ 0.29 0.83 Ϯ 0.32c 2.71 Ϯ 0.55 1.016 Ϯ 0.361d 0.950 Ϯ 0.146 (-), n ϭ 14 36.40 Ϯ 21.90 4.41 Ϯ 1.12 2.70 Ϯ 1.12 1.33 Ϯ 0.36c 2.53 Ϯ 0.75 1.435 Ϯ 0.351d 0.819 Ϯ 0.223 a (ϩ) and (-) indicate individuals with and without the ABCA1 W590L mutation, respectively. Login to comment
87 The W590L mutation site in ABCA1 resides in a highly conserved hydrophobic region within the extracellular segment of the NH2 terminus (24, 25) and is identical to amino acid 605 of ABCR. Login to comment
52 The affected individuals in the kindred were heterozygous for a G2265T substitution (Fig. 2, arrow) with predicted conversion of Trp to Leu (W590L). Login to comment
56 Pedigree of a kindred showing HDL-C segregation of W590L mutation. Login to comment
63 Significant differences between (af9;) and (afa;) individuals for the W590L mutation were noted for HDL-C (P afd; 0.009) and apoA-I (P afd; 0.036). Login to comment
76 Individuala Sex Age, years TC,b mmol/L TG, mmol/L HDL-C, mmol/L LDL-C, mmol/L apoA-I, g/L apoB, g/L I-2 (afa;) F 88 5.43 3.28 1.40 3.39 1.67 1.10 I-3 (d19;) M 81 4.63 2.20 1.06 3.13 1.21 0.95 II-1 (afa;) M 48 4.88 4.34 1.14 2.87 1.32 1.00 II-2 (afa;) F 47 5.53 3.54 1.65 3.18 2.00 1.11 II-3 (d19;) M 52 3.10 2.97 0.34 2.17 0.49 0.93 II-4 (afa;) F 54 3.95 1.63 1.65 1.96 1.54 0.60 II-5 (d19;) M 57 5.19 2.38 1.14 3.59 1.39 1.18 II-6 (afa;) F 54 3.67 1.24 1.14 2.17 1.18 0.64 II-7 (afa;) M 54 7.13 4.91 1.94 4.21 2.05 1.26 II-8 (d19;) F 40 3.80 2.45 0.88 2.43 1.06 0.86 III-1 (afa;) F 19 4.16 2.48 0.96 2.71 1.01 0.79 III-2 (afa;) M 27 3.10 2.43 1.27 1.34 1.51 0.54 III-3 (d19;) M 31 3.70 2.74 0.54 2.61 0.85 0.98 III-4 (d19;) F 28 3.80 2.35 1.03 2.30 1.29 0.80 III-5 (afa;) F 33 3.98 1.52 1.40 2.27 1.34 0.68 III-6 (afa;) F 19 3.95 2.74 0.96 2.45 1.10 0.75 III-7 (afa;) F 27 5.37 2.07 1.96 2.89 1.90 0.93 III-8 (afa;) M 10 3.64 2.25 1.01 2.20 1.15 0.77 III-9 (afa;) M 13 3.70 1.60 1.24 2.14 1.24 0.68 III-10 (afa;) F 17 3.23 3.75 0.88 1.60 1.09 0.62 Mean afe; SD (af9;), n afd; 6 41.60 afe; 12.70 4.04 afe; 0.75 2.52 afe; 0.29 0.83 afe; 0.32c 2.71 afe; 0.55 1.016 afe; 0.361d 0.950 afe; 0.146 (afa;), n afd; 14 36.40 afe; 21.90 4.41 afe; 1.12 2.70 afe; 1.12 1.33 afe; 0.36c 2.53 afe; 0.75 1.435 afe; 0.351d 0.819 afe; 0.223 a (af9;) and (afa;) indicate individuals with and without the ABCA1 W590L mutation, respectively. Login to comment