ABCMdb

ABCA1 p.Pro85Leu

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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
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

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
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: 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: 12921988 [PubMed] Kolovou G et al: "A new ABCA1 mutation associated with low HDL cholesterol but without coronary artery disease."

No. Sentence Comment

0 Letter to the Editor A new ABCA1 mutation associated with low HDL cholesterol but without coronary artery disease We have read with great interest the paper of Seung Ho Hong and associates [1] describing the P85L variant, or ABCA1Alabama , in the ATP-binding cassette transporter (ABCA1) gene, and would like to add some comments and observations that may be of interest. Login to comment
15 Although our patient as well as her parents have a truncated ABCA1 transcript, they have no clinical signs of CAD, while the patient with the P85L variation produces a full length and possibly functional protein, and developed premature CAD which led him to coronary artery bypass grafting at the age of 48 years old. Login to comment

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

No. Sentence Comment

63 FHA 648 C/T 4 P85L extracellular loop # 1 [72.] Login to comment

PMID: 12204794 [PubMed] Hong SH et al: "ABCA1(Alabama): a novel variant associated with HDL deficiency and premature coronary artery disease."

No. Sentence Comment

3 The proband and affected individuals were heterozygotes for C254T with proline converted to leucine (P85L). Login to comment
50 Pedigree of the kindred showing HDL segregation of the P85L mutation. Login to comment
51 Solid symbols indicate heterozygote carrier status for the P85L mutation. Login to comment
73 This mutation changes proline to leucine (P85L). Login to comment
111 Mean plasma lipid levels were compared between carriers ('/) and non-carriers ((/) of the P85L mutation. Login to comment
122 In the present study, the novel mutation (P85L) in ABCA1 was identified in one family with low HDL but was not detected in over 400 chromosomes of healthy subjects. Login to comment
124 The P85L mutation is located in the 5? Login to comment
110 Mean plasma lipid levels were compared between carriers (/) and noncarriers (/) of the P85L mutation. Login to comment
121 In the present study, the novel mutation (P85L) in ABCA1 was identified in one family with low HDL but was not detected in over 400 chromosomes of healthy subjects. Login to comment
123 The P85L mutation is located in the 5? Login to comment

PMID: 24456889 [PubMed] Colin S et al: "HDL does not influence the polarization of human monocytes toward an alternative phenotype."

No. Sentence Comment

39 We included 6 subjects who carried heterozygous mutations in ABCA1: p.Arg587Trp, p.Val618Asp, p.Ser140Ter, p.Pro85Leu, p.Cys1941Arg/c.6402 + 2TNG, 3 subjects with a homozygous mutation in LCAT: p.Thr147Leu/p.Val333Met, p.Thr147Leu and 3 subjects with a heterozygous mutation in LCAT: p.Pro34Gln [19,20]. Login to comment

PMID: 24916532 [PubMed] Ahmadzadeh A et al: "Genes associated with low serum high-density lipoprotein cholesterol."

No. Sentence Comment

26 Homozygosity and heterozygosity mutations in this gene have been associated with Tangier disease, an autosomal-recessive disorder characterized by deposition of cholesterol esters in organs, and familial high-density lipoprotein GH&#bf;FLHQF\UHVSHFWLYHO\28,29 /RZFHOOXODUFKROHVWHUROHI&#c0;X[GXHWR mutant ABCA1 leads to reduced apolipoprotein A-I stability and rapid catabolism of HDL-C.30 Over 90 structural variants have been known to cause low HDL-C, most of which are in coding areas, whereas only a few are located in intronic regions31,32 ; e.g., a single defective allele in exon 4 ABCA1 at C254T changing a proline to a leucine (P85L) may be associated with low HDL-C.33 Lecithin cholesteryl acyl transferase LCAT (16q22.1), a member of the lipase superfamily, is a plasma enzyme synthesized by the liver and the small intestine. Login to comment