ABCMdb

ABCA1 p.Phe2009Ser

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Publications

PMID: 20188211 [PubMed] Koldamova R et al: "The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration."

No. Sentence Comment

95 The second example is a compound heterozygous mutation (D1099Y and F2009S) identified in a subject with severe HDL cholesterol deficiency [16]. 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

11 Materials and methods We previously identified mutations in LCAT [T321M, C-deletion (codon 168) P260X [7,8], ABCA1 [D1099Y, F2009S, P85L, R1851Q, IVS46: del T-39…-46] [9-11] and APOA1 [L159P] [12]. Login to comment
46 Therefore, while we Table 1 Genetic variants causing low HDL-C Gene Mutation Number Affected Reference LCAT c-deletion (codon 168) 2 [7] T321M 5 [7] P260X 3 [8] I178T 6 [13] ABCA1 D1099Y 5 [9] F2009S 1 [9] P85L 4 [10] R1851Q 6 [11] IVS46: del T-39…-46 6 [11] APOAI L159P 6 [12] Total 41 cases (includes 3 compound heterozygotes) Table 2 Selected demographic factors, risk factor prevalence, medication use and biochemical measurements (mean and SD) and cIMT in genetic variant HDL-C cases and controls Cases (n=41) Controls (n=73) Age (y) 44.8 (20.7) 44.8 (19.1) BMI (kg/m2 ) 28.0 (4.3) 26.4 (4.9) Hypertension (%) 10.8% 15.9% Diabetes mellitus (%) 2.7% 0% Smoking history (%) 24.3% 31.7% Antiplatelet therapy (%) 18.9% 9.7% Lipid lowering therapy (%) 21.6% 12.9% cIMT (mm) 0.66 (0.17) 0.65 (0.18) TC (mmol/l) 4.92 (1.52) 5.03 (1.06) TG (mmol/l) 2.10 (1.72) ⁎ 1.36 (0.90) HDL-C (mmol/l) 0.67 (0.36) ⁎ 1.58 (0.75) LDL-C (mmol/l) 3.28 (1.31) 2.85 (0.91) APOAI (mg/dl) 96.7 (37.9) ⁎ 151.4 (34.9) APOB (mg/dl) 123.6 (44.8) ⁎ 89.9 (26.6) ⁎ Pb0.05 cases vs. controls. 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

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 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

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
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

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: 12009425 [PubMed] Ho Hong S et al: "Novel ABCA1 compound variant associated with HDL cholesterol deficiency."

No. Sentence Comment

5 The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). Login to comment
43 Pedigree of the kindred showing HDL segregation of D1099Y and F2009S mutations. Login to comment
44 Horizontal line symbols indicates heterozygote carrier status for the D1099Y mutation. Login to comment
45 The heterozygous subjects for F2009S mutation are indicated by vertical line symbols. Login to comment
71 The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). Login to comment
73 The proband had a compound mutation for D1099Y and F2009S (Fig. 1, arrow). Login to comment
77 The F2009S mutation was also associated with low HDL cholesterol [(+), 17.0 F 18.4 vs. ( À ), 40.6 F 13.9 mg/dl; P < 0.05] and apoA-I [(+), 54.0 F 65.1 vs. ( À ) 114.0 F 28.4 mg/dl; P < 0.05] levels. Login to comment
79 The amino acids at the D1099Y and F2009S mutation sites are conserved between human and mouse, indicating a potentially important biological function. Login to comment
80 The D1099Y Table 2 Positions of ABCA1 exons and sequences of oligonucleotide primers Exon Sequence Annealing Tm (jC) 5 5V-CACTTGGCAGTCACTTCTGT-3V 56 5V-ACGGATGCAGAGAAGGTT-3V 6 5V-TCCTGATATGGCGATGCTCC-3V 56 5V-TGAGGAAGCTGGAGGCATCA-3V 9 5V-CGCCAGCTGTTCAGCATGAG-3V 55 5V-CATCTTCCTCAGTGCCATTG-3V 12 5V-GGATGGCTTAGATTGGACAG-3V 55 5V-CATGAAGCGAGATATGGTCC-3V 17 5V-CAGAGCCTGCTGTCTCCTGT-3V 55 5V-AGACAGCCTCAATGTACCAG-3V 21 5V-CAGGCTGACTGTCGAAGA-3V 55 5V-CCTGACAGCTGGCTTGTT-3V 23 5V-GGCCGCACCATTATTCTCTCT-3V 55 5V-CAGCTCACCTTTTTCAGGTA-3V 25 5V-TGTCTCTGCTATCTCCAACC-3V 55 5V-GTCGTCTCTGAGATGCCATA-3V 27 5V-TCCTTGTGCCTTCAGATGGT-3V 55 5V-GGATCAGCAGCATCATCTTC-3V 28 5V-TGGCTTCTTGCAGAATCC-3V 54 5V-GACTCCGTCTGGCAATTA-3V 29 5V-AGATTGTCTTGCCAGCTGTG-3V 55 5V-CTGTTCGTTGTACATCCAGG-3V 36 5V-CTGGCATGCAATCAGCTCTT-3V 55 5V-ACCTCTGAGAGCTGCTGCTT-3V 37 5V-TTCTCTCCAGGATGACCACA-3V 55 5V-AGAGAGCCAGTAGATGACAG-3V 39 5V-TTGTGTCTCAACAGGTGGTC-3V 55 5V-ACATTGTCGGTGAACAGCTC-3V Exons of the ABCA1 gene are designated by the nomenclature of Santamarina-Fojo et al. [17]. Login to comment
82 On the other hand, the region affected by F2009S mutation is within the C-terminal NBD. Login to comment
46 The heterozygous subjects for F2009S mutation are indicated by vertical line symbols. Login to comment
72 The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). Login to comment
74 The proband had a compound mutation for D1099Y and F2009S (Fig. 1, arrow). Login to comment
78 The F2009S mutation was also associated with low HDL cholesterol [(+), 17.0 F 18.4 vs. ( ), 40.6 F 13.9 mg/dl; P < 0.05] and apoA-I [(+), 54.0 F 65.1 vs. ( ) 114.0 F 28.4 mg/dl; P < 0.05] levels. Login to comment
83 On the other hand, the region affected by F2009S mutation is within the C-terminal NBD. Login to comment

PMID: 22959828 [PubMed] Fasano T et al: "Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency."

No. Sentence Comment

236 This hypothesis is unlikely in view of the fact that this mutation was originally reported by Ho Hong et al. [19] in one patient with extremely low plasma HDL-C and ApoA-I (4 and 8 mg/dL respectively, consistent with the diagnosis of TD) who was in fact a compound heterozygote, carrying another missense mutation (p.F2009S), which segregated with low plasma HDL-C phenotype in the patient's pedigree. Login to comment

PMID: 24844148 [PubMed] Koldamova R et al: "ATP-binding cassette transporter A1: from metabolism to neurodegeneration."

No. Sentence Comment

1001 The second example is a compound heterozygous mutation (D1099Y and F2009S) identified in a subject with severe HDL cholesterol deficiency (Ho Hong et al., 2002). Login to comment