ABCMdb

ABCA1 p.Phe593Leu

None has been submitted yet.

Publications

PMID: 20880529 [PubMed] Candini C et al: "Identification and characterization of novel loss of function mutations in ATP-binding cassette transporter A1 in patients with low plasma high-density lipoprotein cholesterol."

No. Sentence Comment

61 Eight novel missense variations [c.299C > G (p.S100C), c.1724A > G (p.D575G), c.1779C > G (p.F593L), c.3167T > C (p.L1056P), c.3757G > A (p.E1253K), c.4535C > T (p.T1512M), c.5573T > C (p.V1858A), c.5821T > C (p.C1941R)] were introduced into this chimeric construct by site-directed mutagenesis using Stratagene QuikChange XL site-directed mutagenesis kit according to manufacturer`s instructions (La Jolla, CA, USA). Login to comment
76 Patients (gender, age) Amino acida (nucleotidea ) change TC TG LDL-c HDL-c Clinical manifestations of TD CVD Other relevant clinical data Homozygotes Patient 1 (female, 42) p.L1056P (c.3167T > C) 2.4 0.9 1.99 <0.10 Absent CAD Thrombocytopenia Patient 2 (male, 40) p.Wl747X (c.5240G > A) 1.76 1.93 0.52 0.1-0.3 Neuropathy, splenomegaly, thrombocytopenia Mild stenosis (20-30%) of coronary arteries None Patient 3 (male, 55) p.F593L (c.1779C > G) 4.4 1.4 3.6 <0.10 Absent CAD None p.E1253K (c.3757G > A) Compound heterozygotes Patient 4 (female, 63) p.Q1038X (c.3112C > T) 6.68 2.72 5.4 <0.10 Absent None None p.N1800H (c.5398A > C) [32] Patient 5 (female, 28) p.T1512M (c.4535C > T) 4.42 1.83 3.46 0.1 Absent None None p.N1800H (c.5398A > C) [32] p.C978fsX988 (c.2934delT) Patient 6 (female, 17) p.D575G (c.1724A > G) 4.96 2.84 4.35 <0.10 Absent None DM1 p.C1941R(c.5821T > C) Heterozygotes Patient 7 (male, 42) p.S100C (c.299C > G) 8.5 8.7 4.3 0.3 N.A. None None Patient 8 (male, 58) p.E1172D (c.3516G > C) [33] 6.4 2.7 4.1 0.9 N.A. None None Patient 9 (male, 35) p.S1181F (c.3542C > T) [17] 2.9 0.31 1.88 0.88 N.A. None None Patient 10 (male, 48) p.C1477R (c.4429T > C) [13] 2.01 1.4 0.92 0.46 N.A. CAD None Patient 11 (male, 68) p.V1858A (c.5573T > C) 4.9 3.78 2.41 0.75 N.A. CAD None Patient 12 (female, 36) p.N1800H (c.5398A > C) [32] 4.6 1.2 4 <0.10 N.A. None DM2, obesity Patient 13 (male, 67) p.R282X (c.844C > T) [34] 3.2 1.21 2.14 0.51 N.A. None DM2 Patient 14 (female, 42) p.W424X (c.1272G > A) 2.07 1.04 1.39 0.21 N.A. None None Patient 15 (female, 52) N.A. - (IVS11 - 1G > A) 5.51 3.51 3.28 0.56 N.A. None Hypothyroidism, hypertension Patient 16 (female, 54) N.A. - (IVS48 + 2T > C) 3.29 1.92 1.94 0.49 N.A. None DM2, hypertension a Nomenclature based on guidelines of Human Genome Variation Society. Login to comment
89 In ABCA1, we identified 14 novel and 5 known genetic variations in 16 subjects including one frameshift (p.C978fsX988), 2 splice-site (IVS11-1G > C and IVS48 + 2T > C), 4 nonsense (p.R282X, p.W424X, p.Q1038X, p.Wl747X) and 12 missense variations (p.S100C, p.D575G, p.F593L, p.L1056P, p.E1172D, p.S1181F, p.E1253K, p.C1477R, p.T1512M, p.N1800H, p.V1858A, p.C1941R). Login to comment
94 From eight novel missense variations identified in our cohort, one is localized in the first transmembrane domain (p.S100C), two in the first large extracellular loop (p.D575G and p.F593L), two in the first Nuclear Binding Domain (p.L1056P and p.E1253K), one in the second large extracellular loop (p.T1512M), one in the extracellular region, close to the plasma membrane (p.V1858A) and one is localized in the C-terminal domain (p.C1941R). Login to comment
98 Four out of eight mutations were predicted to be probably damaging (p.S100C, p.D575G, p.T1512M, p.C1941R), two as possibly damaging (p.F593L and p.L1056P) and two were described as benign (p.E1253K and p.V1858A) by PolyPhen. Login to comment
110 Fig. 2 shows that the ABCA1-p.S100C, p.D575G, p.F593L, p.L1056P, p.E1253K, p.T1512M, p.C1941R mutant proteins all had a significantly reduced capacity to efflux cholesterol to apo A-I compared to wild-type ABCA1 which is in line with the low HDL cholesterol levels of the individuals in whom the mutations were identified. Login to comment
148 The ABCA1-p.F593L and ABCA1-p.D575G mutations are located in the first large extracellular loop, while ABCA1-p.T1512M is located in the second extracellular loop. Login to comment

PMID: 24097981 [PubMed] Quazi F et al: "Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants."

No. Sentence Comment

65 Mutations introduced by overlap extension PCR using Pfu AD DNA polymerase in ABCA1 included S100C, W590S, F593L, N935S, T929I, C1477R, T1512M, R2081W, and P2150L. Login to comment
67 ABCA1-MM was constructed to harbor the Walker A-motif lysine-to-methionine mutations K939M/K1952M by the nested PCR method; ABCA4-MM had the corresponding K969M/ K1969M Walker A mutations (37), and ABCA7-MM had the Lipid Transport Activity of ABCA Transporters NOVEMBER 29, 2013ߦVOLUME 288ߦNUMBER 48 JOURNAL OF BIOLOGICAL CHEMISTRY 34415 at SEMMELWEIS UNIV OF MEDICINE on December 3, K847M/K1833M Walker A mutations. Login to comment
208 Expression and Purification of Disease-causing ABCA1 and ABCA4 Mutants-As part of this study, we have generated a number of disease-causing mutations in ABCA1 and ABCA4 to determine their effect on the expression and functional properties of these transporters. We focused our studies on nine missense mutations in ABCA1 known to cause Tangier disease, including three (S100C, W590S, and F593L) in ECD1, two (T929I and N935S) in the NBD1, two (C1477R and T1512M) in ECD2, one (R2081W) in NBD2, and one (P2150L) in the C-terminal segment as shown in Fig. 6A (blue). Login to comment
229 Variants in the ECD1 (S100C, W590S, and F593L), NBD1 (T929I and N935S), and NBD2 (R2081W) of ABCA1 showed significantly reduced ATPase activities in the range of 20-35% of WT activity (Fig. 7A). Login to comment
232 ABCA4 variants showed a similar ATPase activity profile as the ABCA1 mutants with the exception of the T1537M mutation of ABCA4, which was significantly lower than the corresponding T1512M mutant in ABCA1. Login to comment
295 The ABCA1/ABCA4 mutants in the ECD1 (S100C/S100P, W590S/ W605S, and F593L/F608L) displayed the lowest activities (20-30% WT), whereas those in the ECD2 (C1477R/C1502R and T1512M/T1537M) and the P2150L/P2180L mutants in the C terminus showed the highest activities (60-100% WT). Login to comment
211 Expression and Purification of Disease-causing ABCA1 and ABCA4 Mutants-As part of this study, we have generated a number of disease-causing mutations in ABCA1 and ABCA4 to determine their effect on the expression and functional properties of these transporters. We focused our studies on nine missense mutations in ABCA1 known to cause Tangier disease, including three (S100C, W590S, and F593L) in ECD1, two (T929I and N935S) in the NBD1, two (C1477R and T1512M) in ECD2, one (R2081W) in NBD2, and one (P2150L) in the C-terminal segment as shown in Fig. 6A (blue). Login to comment
298 The ABCA1/ABCA4 mutants in the ECD1 (S100C/S100P, W590S/ W605S, and F593L/F608L) displayed the lowest activities (20-30% WT), whereas those in the ECD2 (C1477R/C1502R and T1512M/T1537M) and the P2150L/P2180L mutants in the C terminus showed the highest activities (60-100% WT). Login to comment
64 Mutations introduced by overlap extension PCR using Pfu AD DNA polymerase in ABCA1 included S100C, W590S, F593L, N935S, T929I, C1477R, T1512M, R2081W, and P2150L. Login to comment
206 Expression and Purification of Disease-causing ABCA1 and ABCA4 Mutants-As part of this study, we have generated a number of disease-causing mutations in ABCA1 and ABCA4 to determine their effect on the expression and functional properties of these transporters. We focused our studies on nine missense mutations in ABCA1 known to cause Tangier disease, including three (S100C, W590S, and F593L) in ECD1, two (T929I and N935S) in the NBD1, two (C1477R and T1512M) in ECD2, one (R2081W) in NBD2, and one (P2150L) in the C-terminal segment as shown in Fig. 6A (blue). Login to comment
227 Variants in the ECD1 (S100C, W590S, and F593L), NBD1 (T929I and N935S), and NBD2 (R2081W) of ABCA1 showed significantly reduced ATPase activities in the range of 20-35% of WT activity (Fig. 7A). Login to comment
293 The ABCA1/ABCA4 mutants in the ECD1 (S100C/S100P, W590S/ W605S, and F593L/F608L) displayed the lowest activities (2030% WT), whereas those in the ECD2 (C1477R/C1502R and T1512M/T1537M) and the P2150L/P2180L mutants in the C terminus showed the highest activities (60-100% WT). Login to comment