ABCMdb

ABCA1 p.Met1091Thr

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Publications

PMID: 21875686 [PubMed] Tietjen I et al: "Increased risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT."

No. Sentence Comment

117 COOHA B T929I H2N R587W B A M1091T C1477R K776N N935S S1181F IVS24+1 G>C V2244I R282X D571G M640L S930F M968T R1615WIVS16-5 CA>del ABCA1 Transmembrane domain ATP-binding domain Q597R A) AA 1 AA 267 K130del L202P 74 90 98 112 122 145 167 189 211 215 233 253 APOA1 Negative charge domain Alpha-helix E222K E134DT37M 140 178 206 41127 104 121 165 200 229 360 391 Y135N V246F 127 206 369 401 Catalytic triad R322C L338H V371MV52M Y107X A117T T147I V333M Phe Leu Asp His AA 1 AA 440 R159Q I202T LCAT Alpha helixBeta sheet B) 419I.Tietjenetal./BiochimicaetBiophysicaActa1821(2012)416-424 3.4. Login to comment
169 Effects of some ABCA1 mutations described here are also consistent with previous in vitro cellular efflux studies; for example, the highly expressive ABCA1 mutations R587W, Q597R, N935S, and M1091T cause ~10-25% of wild-type efflux in vitro, while the less expressive mutations K776N and T929I cause 62 and 80% efflux, respectively [35-37]. Login to comment

PMID: 20418488 [PubMed] Acuna-Alonzo V et al: "A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans."

No. Sentence Comment

99 (A) Polyclonal stable cell lines expressing the ABCA1 wild-type (WT), variant R230C and mutant M1091T (known defective in lipid efflux) were generated, and efflux activity for cholesterol was performed as described in Materials and Methods. Login to comment
103 (B) The expression of WT, variant R230C and mutant M1091T ABCA1 protein in Flp-In cells was assessed by western immunoblotting. Login to comment
151 The M1091T ABCA1 mutation previously identified in Tangier patients was used as control (32). Login to comment
101 (A) Polyclonal stable cell lines expressing the ABCA1 wild-type (WT), variant R230C and mutant M1091T (known defective in lipid efflux) were generated, and efflux activity for cholesterol was performed as described in Materials and Methods. Login to comment
105 (B) The expression of WT, variant R230C and mutant M1091T ABCA1 protein in Flp-In cells was assessed by western immunoblotting. Login to comment
153 The M1091T ABCA1 mutation previously identified in Tangier patients was used as control (32). Login to comment

PMID: 20067955 [PubMed] Vergeer M et al: "Carriers of loss-of-function mutations in ABCA1 display pancreatic beta-cell dysfunction."

No. Sentence Comment

46 Subjects included in the present study were heterozygous carriers of the following extremely rare ABCA1 mutations: C1477R, M1091T, and R587W (4,7-10) and L996P and Q978X (C. Candini et al., manuscript in preparation). Login to comment
48 C1477R has been reported in nine heterozygous individuals, M1091T in four individuals, and R587W in seven individuals (11). Login to comment
93 Carriers were recruited from five different families (four C1477R carriers, three M1091T carriers, three R587W carriers, four L996P carriers, and one Q978X carrier); family control subjects were siblings, cousins, or partners of a carrier. Login to comment
103 This group consisted of four C1477R carriers, two M1091T carriers, one L996P carrier, one Q978X carrier, and eight control subjects. Login to comment
47 Subjects included in the present study were heterozygous carriers of the following extremely rare ABCA1 mutations: C1477R, M1091T, and R587W (4,7-10) and L996P and Q978X (C. Candini et al., manuscript in preparation). Login to comment
49 C1477R has been reported in nine heterozygous individuals, M1091T in four individuals, and R587W in seven individuals (11). Login to comment
95 Carriers were recruited from five different families (four C1477R carriers, three M1091T carriers, three R587W carriers, four L996P carriers, and one Q978X carrier); family control subjects were siblings, cousins, or partners of a carrier. Login to comment
105 This group consisted of four C1477R carriers, two M1091T carriers, one L996P carrier, one Q978X carrier, and eight control subjects. Login to comment

PMID: 20656214 [PubMed] Kang MH et al: "Adenosine-triphosphate-binding cassette transporter-1 trafficking and function."

No. Sentence Comment

40 The importance of ABCA1 localization to the PM is observed in several mutations underlying TD (R587W, Q597R, ΔL693, M1091T), where mislocalization of ABCA1 away from the cell surface leads to a significant reduction in cholesterol efflux function (Singaraja et al. 2006). Login to comment

PMID: 19556522 [PubMed] Singaraja RR et al: "Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function."

No. Sentence Comment

125 As a control, cells expressing the ABCA1 mutant M1091T were used. Login to comment
147 Circulation Research July 17, 2009 at harboring the naturally occurring ABCA1 mutation M1091T that was previously characterized as severe loss-of-function mutation8 was reduced by Ϸ80%. Login to comment
156 The severe loss-of-function patient mutation M1091T, previously shown to be absent from the plasma membrane, was used as a positive control. Login to comment
177 As a control, efflux of lipids was reduced by Ϸ80% in a cell line harboring M1091T, a naturally occurring loss-of-function patient mutation. Login to comment
209 As controls for the efflux assay, we used a cell line harboring M1091T, a naturally occurring patient mutation that was previously characterized as severe loss-of-function mutation8 and showed Ͼ80% reduction in efflux, likely representing the absence of ABCA1 both at the plasma membrane and at intracellular sites of function. Login to comment
120 As a control, cells expressing the ABCA1 mutant M1091T were used. Login to comment
142 Circulation Research July 17, 2009 harboring the naturally occurring ABCA1 mutation M1091T that was previously characterized as severe loss-of-function mutation8 was reduced by b07;80%. Login to comment
151 The severe loss-of-function patient mutation M1091T, previously shown to be absent from the plasma membrane, was used as a positive control. Login to comment
172 As a control, efflux of lipids was reduced by b07;80% in a cell line harboring M1091T, a naturally occurring loss-of-function patient mutation. Login to comment
204 As controls for the efflux assay, we used a cell line harboring M1091T, a naturally occurring patient mutation that was previously characterized as severe loss-of-function mutation8 and showed b0e;80% reduction in efflux, likely representing the absence of ABCA1 both at the plasma membrane and at intracellular sites of function. Login to comment

PMID: 18706283 [PubMed] Iatan I et al: "Effect of ABCA1 mutations on risk for myocardial infarction."

No. Sentence Comment

119 Genetic variation in ABCA1 and risk of myocardial infarction Study* / year Population screened HDL-C, mmol/L ABCA1 variants Conclusions Clee et al. [28] / 2000 Within 11 TD families: Del L693, R2144X † , Del E,D1893,94 † , R909X, M1091T † , P2150L † , ivs25+1G→C, Del C6825→2145X, CTC6952- 4TT→2203X, C1477R, Q597R, T929I ABCA1 heterozygous patients had a 40%-45% decrease in HDL-C and a greater than threefold increased risk of CHD versus unaffected individuals. Login to comment

PMID: 16873719 [PubMed] Singaraja RR et al: "Specific mutations in ABCA1 have discrete effects on ABCA1 function and lipid phenotypes both in vivo and in vitro."

No. Sentence Comment

43 In ABCA1 heterozygotes, 3 distinct phenotypic groups emerged, one in which HDL-C levels were Ϸ50% of those of age-and sex-matched controls, one in which HDL-C levels were at least 70% of controls (A255T, W590S, T929I), and one in which HDL-C levels were significantly below the expected 50% of the levels for controls (30.4% of controls) (M1091T) (Table). Login to comment
92 Indeed the loss of function mutations showed an intermediate phenotype compared with the mutants with partial function, and the putative dominant negative mutant M1091T showed the most severe phenotype. Login to comment
97 <50% of Normal HDL-C Levels in ABCA1 Heterozygotes Imply a Dominant-Negative Function for the Mutant Allele Of the ABCA1 heterozygotes described thus far, only 1 missense mutation, M1091T, results in HDL-C levels that are Figure 3. Login to comment
107 A significant reduction in biotinylated M1091T was observed, thus corroborating the intracellular localization and EndoH data (Figure 4C). Login to comment
109 Patients heterozygous for this mutation have only 36% of normal relative efflux levels.4 These findings, along with the Ϸ30% of normal HDL-C levels observed in patients harboring this mutation, led us to hypothesize that M1091T acted in a dominant-negative manner and prevented the functioning of the normal ABCA1 allele. Login to comment
118 A, The M1091T mutant was retained in an intracellular compartment and did not reach the plasma membrane. Login to comment
119 B, Endo H digestion of M1091T showed that it was localized to the ER. Login to comment
120 C, Cell surface biotinylation of M1091T confirmed its lack of localization at the plasma membrane compared with wild-type ABCA1. Login to comment
121 D, The M1091T mutant showed a significant reduction in its ability to induce ApoA-I binding. Login to comment
122 A significant reduction in the ability of M1091T to promote efflux of both phosphocholine (E) and cholesterol efflux (F) to ApoA-I acceptors was observed. Login to comment
164 One mutant, M1091T, when present in heterozygous patients, results in significantly lower than 50% of normal HDL-C and efflux levels. Login to comment
169 Thus M1091T may act in a dominant-negative manner by an as of yet unknown mechanism. Login to comment
166 One mutant, M1091T, when present in heterozygous patients, results in significantly lower than 50% of normal HDL-C and efflux levels. Login to comment
171 Thus M1091T may act in a dominant-negative manner by an as of yet unknown mechanism. Login to comment

PMID: 16704350 [PubMed] Brunham LR et al: "Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis."

No. Sentence Comment

554 Conversely, a small number of mutations are associated with less than 50% of control HDL cholesterol, specifically M1091T, G1216V, and the truncation mutations R2144X, R282X, and R909X. Login to comment
555 Since a complete loss of function allele would be expected to result in a 50% reduction in HDL levels, a greater than 50% reduction in HDL is most likely explained by a dominant negative allele, in which TABLE 3 Patient phenotypes associated with heterozygous ABCA1 mutations Mutation HDL (mmol/L) HDL (% of control) Number of patients M1091T 0.48 ± 0.5 30 ± 30 4 G1216V 0.50 40 1 R2144X 0.56 ± 0.2 41 ± 18 12 R282X 0.52 41 1 R909X 0.59 ± 0.3 42 ± 19 5 K776N 0.55 ± 0.1 47 ± 5 2 R587W 0.61 ± 0.1 47 ± 8 7 S364C 0.60 48 1 P1065S 0.80 51 1 c-ter deletion 0.75 53 1 N1800H - 56.5 33 P85L 0.72 ± 0.4 57 ± 33 5 Del693L 0.79 ± 0.2 57 ± 15 8 D1289N 0.80 ± 0.1 59 ± 12 4 R2081W 0.80 ± 0.1 59 ± 12 4 2203X 0.80 ± 0.2 59 ± 20 4 DelED1893,4 0.77 ± 0.2 59 ± 18 8 2145X 0.82 ± 0.1 59 ± 9 4 A1046D 0.70 ± 0.1 60 ± 8 2 Q597R 0.82 ± 0.1 60 ± 5 5 C1477R 0.82 ± 0.2 61 ± 15 9 IVS25 + 1G > C 0.78 ± 0.1 62 ± 12 4 D1099Y 0.83 ± 0.3 63 ± 21 5 1552X 1.00 64 1 F2009S 0.82 ± 0.2 64 ± 19 6 R587W 0.86 ± 0.1 65 ± 17 2 R1068H 0.90 ± 0.3 67 ± 26 9 N935S 1.00 ± 0.3 74 ± 16 7 T929I 1.01 ± 0.2 76 ± 7 8 1284X 1.11 ± 0.2 83 ± 14 5 A937V 1.15 ± 0.6 85 ± 28 2 R1680W 1.22 ± 0.2 87 ± 17 3 635X 1.24 ± 0.5 90 ± 32 7 W590S 1.32 ± 0.6 103 ± 46 15 the mutant protein actually interferes with the activity of the remaining wild-type protein. 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 0;4.21 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
61 Of all ABCA1 alleles tested functionally, M1091T displays the greatest reduction in cholesterol efflux (6.9 6 20% of wild-type ABCA1), consistent with previous reports that this is a severe mutation associated with a severe clinical presentation [4,13]. Login to comment
63 To determine whether the severe phenotype conferred by the M1091T mutation is a result of the sensitivity of this site, or rather is specific to the insertion of the threonine residue, we generated and characterized cell lines transfected with plasmids bearing M1091L and M1091V alleles, both predicted to have no impact on ABCA1 function (subPSEC scores À2.65 and À2.71, respectively). Login to comment
64 Interestingly, both of these mutations dramatically impair cholesterol efflux, to a similar extent as the M1091T mutation (Figure 2B). Login to comment
75 Cholesterol Efflux Values for 293 Cells Transfected with ABCA1 Variants and subPSEC and PolyPhen Predictions of the Functional Impact of these Variants Variant Variant Type subPSEC Cholesterol Efflux PolyPhen R2081W Mutation À8.08 21.1 6 21%* Probably damaging N935S Mutation À7.53 29.3 6 13%* Benign A1046D Mutation À7.52 16.8 6 7%* Possibly damaging Q597R Mutation À7.15 17.7 6 14%* Probably damaging R587W Mutation À6.04 31.7 6 33%* Probably damaging C1477R Mutation À5.44 20.5 6 10%* Probably damaging W590S Mutation À5.19 47.1 6 13%* Probably damaging S1506L Mutation À5.17 17.8 6 15%* Probably damaging T929I Mutation À4.29 69.9 6 11%* Possibly damaging N1800H Mutation À4.23 31.3 6 16%* Possibly damaging S1731C SNP À4.21 12.3 6 10%* Possibly damaging M1091T Mutation À3.56 6.9 6 20%* Probably damaging P2150L Mutation À2.88 88.4 6 21% Probably damaging V771M SNP À2.86 145.4 6 33% Benign D1289N Mutation À2.48 137.7 6 86% Benign I883M SNP À1.38 69.1 6 16%* Benign R219K SNP À0.57 103.7 6 21.05 Benign Wild-type - 0.0 100% - *p , 0.01 compared to wild-type ABCA1. Login to comment
87 (B) Cholesterol efflux was assessed in 293 cells stably transfected with wild-type, M1091T, M1091L, or M1091V ABCA1 alleles. Login to comment
138 The subPSEC score for the naturally occurring M1091T mutation (À3.56) is only marginally predictive of a negative impact on function, but this variant resulted in a severe reduction in ABCA1 function, consistent with the severe phenotype observed in patients harboring this mutation [4,13]. Login to comment
142 Therefore, when calculating amino acid probabilities for position 1091, the subPSEC method includes sequences from only ABCA1 and ABCA4, which represents enough sequence variability to predict that a relatively radical mutation such as M1091T will likely be deleterious but not enough to predict that relatively conservative mutations such as M1091L or M1091V will be deleterious. Login to comment

PMID: 14644402 [PubMed] Kuivenhoven JA et al: "Heterozygosity for ABCA1 gene mutations: effects on enzymes, apolipoproteins and lipoprotein particle size."

No. Sentence Comment

49 In family 2, two sisters with near complete HDL deficiency (HDL-cholesterol levels of 0.06 and 0.1 mmol/l, respectively) were found to only be heterozygous for a missense mutation (T3212C) resulting in M1091T. Login to comment
185 The material and method section describes that we have excluded two female heterozygotes of family 2 who presented with a remarkable HDL-deficiency (0.1 and 0.06 mmol/l, respectively) but were only found to be heterozygous for the M1091T defect. Login to comment
186 Heterozygosity for the same mutation surprisingly only resulted in half normal HDL-cholesterol in two of their sisters indicating that dominant-negative effects of M1091T are unlikely as was recently described for ABCA1 truncation mutations [38]. Login to comment

PMID: 12763760 [PubMed] Singaraja RR et al: "Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene."

No. Sentence Comment

83 TABLE 2. Conservation of Amino Acid Residues Mutated in Humans Mutation H. sapiens M. musculus G. gallus D. melanogaster C. elegans P85L P P P ⅐ ⅐ ⅐ P R230C R R R P G A255T A A S ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ R587W R R R ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ W590S W W W R Q Q597R Q Q Q Q Q ⌬L693 L L L L L T929I T T T T T N935S/H N N N N N A937V A A A A A A1046D A A A A A M1091T M M M M M D1099Y D D D D D D1289L/N D D D D D C1477R C C C ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ S1506L S S S ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ N1611D N N N N S R1680W R R R R R N1800H N N N A W F2009S F F F I M R2081W R R R R R P2150L P P P R N ⌬E1893 E E E D S ⌬D1894 D D D D D Twenty-three of 24 (95.83%) amino acids affected by mutations are conserved with G. gallus, reflecting the functional importance of these residues. Login to comment
124 This could be caused by dominant-negative effects of ABCA1, as previously shown for truncation mutations.69 Patients harboring the mutation M1091T show HDL-C levels that are 30% of age-and sex-matched controls.70 This finding suggests that ABCA1 acts as a dimer or as part of a complex in the exertion of its function. Login to comment
136 Single Nucleotide Polymorphisms in the ABCA1 Gene Nucleotide Amino Acid Exon -1095A/G Promoter ⅐ ⅐ ⅐ -477C/T Promoter ⅐ ⅐ ⅐ -419A/C Promoter ⅐ ⅐ ⅐ -320G/C Promoter ⅐ ⅐ ⅐ -191G/C Promoter ⅐ ⅐ ⅐ C69T 5ЈUTR 1 C117G 5ЈUTR 1 InsG319 5ЈUTR 2 G378C 5ЈUTR 2 G1051A R219K 7 T1591C V399A 11 G2706A V771M 16 A2715C T774P 16 G2723C K776N 16 G2826A V825I 17 A3044G I883M 18 G3911C E1172D 24 G5255A R1587K 35 C5587G S1731C 38 markers, namely, increased arterial wall thickness and ABCA1-mediated cholesterol efflux, was performed.73 The study group consisted of 30 individuals heterozygous for 4 different missense mutations in the ABCA1 gene, C1477R, M1091T, P2150L, and T929I. Login to comment
75 TABLE 2. Conservation of Amino Acid Residues Mutated in Humans Mutation H. sapiens M. musculus G. gallus D. melanogaster C. elegans P85L P P P ዼ ዼ ዼ P R230C R R R P G A255T A A S ዼ ዼ ዼ ዼ ዼ ዼ R587W R R R ዼ ዼ ዼ ዼ ዼ ዼ W590S W W W R Q Q597R Q Q Q Q Q èc;L693 L L L L L T929I T T T T T N935S/H N N N N N A937V A A A A A A1046D A A A A A M1091T M M M M M D1099Y D D D D D D1289L/N D D D D D C1477R C C C ዼ ዼ ዼ ዼ ዼ ዼ S1506L S S S ዼ ዼ ዼ ዼ ዼ ዼ N1611D N N N N S R1680W R R R R R N1800H N N N A W F2009S F F F I M R2081W R R R R R P2150L P P P R N èc;E1893 E E E D S èc;D1894 D D D D D Twenty-three of 24 (95.83%) amino acids affected by mutations are conserved with G. gallus, reflecting the functional importance of these residues. Login to comment
116 This could be caused by dominant-negative effects of ABCA1, as previously shown for truncation mutations.69 Patients harboring the mutation M1091T show HDL-C levels that are 30% of age-and sex-matched controls.70 This finding suggests that ABCA1 acts as a dimer or as part of a complex in the exertion of its function. Login to comment
128 Single Nucleotide Polymorphisms in the ABCA1 Gene Nucleotide Amino Acid Exon afa;1095A/G Promoter ዼ ዼ ዼ afa;477C/T Promoter ዼ ዼ ዼ afa;419A/C Promoter ዼ ዼ ዼ afa;320G/C Promoter ዼ ዼ ዼ afa;191G/C Promoter ዼ ዼ ዼ C69T 5b18;UTR 1 C117G 5b18;UTR 1 InsG319 5b18;UTR 2 G378C 5b18;UTR 2 G1051A R219K 7 T1591C V399A 11 G2706A V771M 16 A2715C T774P 16 G2723C K776N 16 G2826A V825I 17 A3044G I883M 18 G3911C E1172D 24 G5255A R1587K 35 C5587G S1731C 38 Singaraja et al Clinical and Biochemical Impact of ABCA1 Variants markers, namely, increased arterial wall thickness and ABCA1-mediated cholesterol efflux, was performed.73 The study group consisted of 30 individuals heterozygous for 4 different missense mutations in the ABCA1 gene, C1477R, M1091T, P2150L, and T929I. Login to comment

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

No. Sentence Comment

66 TD 1591 T/C 11 V399A extracellular [68] TD 1979 (110bpAlu Ins) 12 truncated truncation [60] TD/FHA 2154 C/T 14 R587W extracellular [67,69] TD 2164 G/C 14 W590S extracellular [61] TD 2185 A/G 14 Q597R extracellular [59,67] TD 2219 G/del 14 truncated, 635X truncated [60,61] FHA 2472-2474 3bp del 15 Del L693 TM domain #3 [59] phosphorylation 2706 G/A 16 V771M extracellular [68] 2715 A/C 16 T774P extracellular [68] 2723 G/C 16 K776N extracellular [68] 2868 G/A 17 V825I TM domain #6 [67,68] TD/FHA 3044 A/G 18 I883M cytoplasmic [68] phosphorylat site FHA 3120 C/T 19 R909X truncation [63,71] TD 3181 C/T 19 T929I cytoplasmic [62] TD 3199 A/G 19 N935S Walker A [61] TD 3205 C/T 19 A937V Walker A [61] TD 3532 C/A 22 A1046D cytoplasmic, Walker A/B [70] FHA 3667 T/C 23 M1091T cytoplasmic [63] 3690 G/T 23 D1099Y cytoplasmic [9] TD 3738 2bp del 23 1145X truncation [66] FHA 3911 G/C 24 E1172D linker/cytoplasmic [68] FHA 4242 4bp del 27 1297X truncated [64] TD 4260 G/A 27 D1289N linker cytoplasm [64,65] TD 4824 T/C 31 C1477R extracellular [59] TD 4912 C/T 32 S1506L extracellular loop #2 [71] TD 5025 ins A 34 A1544S?1552X truncation [70] 5059 T/C 34 I1555T extracellular loop #2 [67] 5155 G/A 35 R1587K extracellular loop #2 [68] FHA 5226 A/G 36 N1611D extracellular loop #2 [75..] 5338 T/C 36 L1648P extracellular loop #2 [67] TD 5443 C/T 37 R1680W cytoplasmic [74.] Login to comment

PMID: 12700344 [PubMed] Hovingh GK et al: "The role of the ABCA1 transporter and cholesterol efflux in familial hypoalphalipoproteinemia."

No. Sentence Comment

81 The two compound heterozygous patients have been described previously [one of the compound heterozygous carriers suffered from a missense mutation (T to C at position 4,369) resulting in a C1477R, and a defect (IVS24 ϩ 1G to C) that caused differential splicing, whereas the other was shown to carry a missense mutation (C to T at position 3,181 resulting in T929I) and a de novo nonsense mutation] (16). Login to comment
82 A missense mutation (T3212C) resulting in M1091T, and a C to T nucleotide substitution at position 6,844 resulting in P2150L were the defects in the two heterozygous carriers. Login to comment

PMID: 12642355 [PubMed] Marcil M et al: "Cellular phospholipid and cholesterol efflux in high-density lipoprotein deficiency."

No. Sentence Comment

85 Molecular Characterization of ABCA1 Gene in Study Subjects Cell Lines HDL-C, mmol/L Nucleotide Change Predicted Protein Alteration TD CTL-1 0.10 Exon 30 T4369C; exon 24 splice site G3C C1477R; part of the transcript deleted TD CTL-2 0.15 Exon 13 A1730G Q597R FHD-1 0.40 Exon 14 ⌬2017-9 ⌬L693 FHD-2 0.18 Exon 48 C6370T R2144X FHD-3 0.39 Exon 41 ⌬5618-23 ⌬ED1893,4 FHD-4 0.18 Exon 18 C2665T R909X FHD-5 0.10 Exon 23 T3667C M1091T FHD-6 0.57 Exon 49 C6844T P2150L, R587W TD-1 0.03 Exon 48 ⌬C6370; ND 2145X TD-2 0.07 ND ND TD-3 0.03 ND 2203X TD-4 0.09 Exon 19 C3181T; ND T929I; ND CTL indicates control. Login to comment
79 Molecular Characterization of ABCA1 Gene in Study Subjects Cell Lines HDL-C, mmol/L Nucleotide Change Predicted Protein Alteration TD CTL-1 0.10 Exon 30 T4369C; exon 24 splice site G3C C1477R; part of the transcript deleted TD CTL-2 0.15 Exon 13 A1730G Q597R FHD-1 0.40 Exon 14 èc;2017-9 èc;L693 FHD-2 0.18 Exon 48 C6370T R2144X FHD-3 0.39 Exon 41 èc;5618-23 èc;ED1893,4 FHD-4 0.18 Exon 18 C2665T R909X FHD-5 0.10 Exon 23 T3667C M1091T FHD-6 0.57 Exon 49 C6844T P2150L, R587W TD-1 0.03 Exon 48 èc;C6370; ND 2145X TD-2 0.07 ND ND TD-3 0.03 ND 2203X TD-4 0.09 Exon 19 C3181T; ND T929I; ND CTL indicates control. 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."

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131 Expression data by mutation Family Mutation Proteinc Induced/Uninduced HDL-C Net Effluxd mmol/l % of control FHA1 Del L 693 5.95 (0.82) 0.4 79.47 (22.63) FHA2 R2144X 2.45 (0.19) 0.18 64.01 (11.12) FHA3 Del E,D 1893, 1894 7.82 (1.48) 0.39 60.03 (11.85) FHA4 R909X 2.32 (0.52) 0.18 72.28 (18.01) FHA5 M1091T 6.42 (0.29) 0.1 47.24 (3.79) TD1 ivs2511G-C, C1477R 3.46 (0.50) 0.1 2.73 (1.05) TD1-ha C1477R 10.28 (1.07) 0.9 58.14 (5.49) TD3 GG 5277C - 1636 2.89 (0.59) 0.09 23.3 (1.29) TD3-hb T9291 6.65 (0.10) 1.12 51.8 (1.30) TD4 Del C 6825 - 2145X, unidentified 1.14 (0.13) 0.03 17.22 (0) Control None 11.31 (0.68) 1.63 100.00 (7.09) a TD1-h is the heterozygous parent of the TD1 proband. Login to comment

PMID: 11809185 [PubMed] van Dam MJ et al: "Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study."

No. Sentence Comment

52 The ABCA1 mutations in NL-014 and NL-016, which have been previously described, consist of 4369T→C (C1477R) and 3212T→C (M1091T), respectively.6,9 Mutation carriers from the two newly discovered families with familial hypoalphalipoproteinaemia NL-020 and NL-016 had a 6844C→T (P2150L) and a 3181C→T (T929I) mutation in the ABCA1 gene respectively. Login to comment

PMID: 20799350 [PubMed] Kelly L et al: "Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains."

No. Sentence Comment

50 Disease-associated nsSNPs at Three Structural Hotspots in Human ABC Transporter NBDs Gene Disease Position ARA motif ABCB11 BRIC2 A570T ABCD1 X-ALD A616V CFTR CF A559T ABCC6 PXE R765Q ABCC8 HHF1 R841G ABCC8 HHF1 R1493Q ABCC8 HHF1 R1493W ABCD1 X-ALD R617C ABCD1 X-ALD R617G ABCD1 X-ALD R617H CFTR CF R560K CFTR CF R560S CFTR CF R560T ABCA1 HDLD1 A1046D ABCB4 ICP A546D C-loop 1 motif ABCC8 HHF1 D1471H ABCC8 HHF1 D1471N CFTR CBAVD G544V ABCC8 HHF1 G1478R C-loop2 motif ABCA4 STGD1 H2128R ABCC8 HHF1 K889T ABCD1 X-ALD R660P ABCD1 X-ALD R660W ABCA1 HDLD2 M1091T ABCA4 STGD1 E2131K ABCA12 LI2 E1539K ABCA4 STGD1 and CORD3 E1122K CFTR CF L610S ABCC8 HHF1 L1543P ABCA1 Colorectal cancer sample; somatic mutation A2109T ABCC9 CMD1O A1513T ABCD1 X-ALD H667D CFTR CF A613T ABCA1 HDLD2 D1099Y ABCD1 X-ALD T668I CFTR CF D614G ABCA4 STGD1 R2139W ABCA4 STGD1 R1129C ABCA4 ARMD2, STGD1, and FFM R1129L Disease abbreviations are as follows: BRIC2, benign recurrent intrahepatic cholestasis type 2; X-ALD, X-linked adrenoleukodystrophy; CF, cystic fibrosis; PXE, Pseudoxanthoma elasticum; HHF1, familial hyperinsulinemic hypoglycemia-1; HDLD1, high density lipoprotein deficiency type 1; ICP, intrahepatic cholestasis of pregnancy; CBAVD, congenital bilateral absence of the vas deferens; STGD1, Stargardt disease type 1; HDLD2, high density lipoprotein deficiency type 2; LI2, ichthyosis lamellar type 2; CORD3, cone-rod dystrophy type 3; CMD1O, cardiomyopathy dilated type 1O; ARMD2, age-related macular degeneration type 2; FFM, fundus flavimaculatus. Login to comment

PMID: 26616730 [PubMed] Murano T et al: "Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation."

No. Sentence Comment

124 The mutations, Pro1065Ser and Met1091Thr, have been shown to disturb the ATP-binding function; these mutations cause FHA [7,19,21, 26]. Login to comment