ABCMdb

PMID: 18716917

George Priya Doss C, Rajasekaran R, Sudandiradoss C, Ramanathan K, Purohit R, Sethumadhavan R
A novel computational and structural analysis of nsSNPs in CFTR gene.
Genomic Med. 2008 Jan;2(1-2):23-32. Epub 2008 May 14., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Phe508Cys Structure analysis was carried out with the major mutation that occurred in the native protein coded by CFTR gene, and which is at amino acid position F508C for nsSNP with id (rs1800093). Login to comment 114 ABCC7 p.Phe508Cys The nsSNP with an id (rs1800093) showed a SIFT tolerance index of 0.00 and PSIC score difference 3.0 at position F508C and was selected for modeling analysis. Login to comment 125 ABCC7 p.Asp1270Asn ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Met1101Lys ABCC7 p.Ser1235Arg ABCC7 p.Phe508Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys ABCC7 p.Leu997Phe ABCC7 p.Ile1027Thr ABCC7 p.Arg1162Leu ABCC7 p.Arg170His ABCC7 p.Leu967Ser ABCC7 p.Phe693Leu ABCC7 p.Ile507Val ABCC7 p.Ala1067Val ABCC7 p.Ile506Met ABCC7 p.Arg1453Trp ABCC7 p.Val562Ile ABCC7 p.Val470Met ABCC7 p.Thr1220Ile ABCC7 p.Ile807Met ABCC7 p.Phe433Leu ABCC7 p.Thr351Ser ABCC7 p.Leu467Phe ABCC7 p.Gln353His ABCC7 p.Ser909Ile ABCC7 p.Leu138Pro ABCC7 p.Tyr903His ABCC7 p.Lys532Glu ABCC7 p.Arg1102Lys ABCC7 p.Val11Cys ABCC7 p.Ser182Gly ABCC7 p.Ser605Phe ABCC7 p.Asn417Lys ABCC7 p.Ser654Gly ABCC7 p.Asp44Val The nsSNPs which were predicted to be Table 1 List of nsSNPs that were predicted to be deleterious by SIFT and PolyPhen SNPs ID Alleles AA change Tolerance index PSIC rs1800072 G/A V11C 1.00 0.150 rs1800073 C/T R31C 0.18 2.288 rs1800074 A/T D44V 0.01 2.532 rs1800076 G/A R75Q 0.03 1.754 rs1800078 T/C L138P 0.01 2.192 rs35516286 T/C I148T 0.41 1.743 rs1800079 G/A R170H 0.05 1.968 rs1800080 A/G S182G 0.03 1.699 rs1800086 C/G T351S 0.30 1.600 rs1800087 A/C Q353H 0.03 2.093 rs4727853 C/A N417K 1.00 0.015 rs11531593 C/A F433L 0.65 0.694 rs1800089 C/T L467F 0.15 1.568 rs213950 G/A V470M 0.17 1.432 rs1800092 C/A/G I506M 0.00 1.574 rs1801178 A/G I507V 0.38 0.314 rs1800093 T/G F508C 0.00 3.031 rs35032490 A/G K532E 1.00 1.525 rs1800097 G/A V562I 0.13 0.345 rs41290377 G/C G576A 0.33 1.262 rs766874 C/T S605F 0.03 2.147 rs1800099 A/G S654G 0.03 1.611 rs1800100 C/T R668C 0.01 2.654 rs1800101 T/C F693L 0.61 0.895 rs1800103 A/G I807M 0.01 1.554 rs1800106 T/C Y903H 0.52 0.183 rs1800107 G/T S909I 0.10 1.624 rs1800110 T/C L967S 0.07 1.683 rs1800111 G/C L997F 0.24 1.000 rs1800112 T/C I1027T 0.03 1.860 rs1800114 C/T A1067V 0.04 1.542 rs36210737 T/A M1101K 0.05 2.637 rs35813506 G/A R1102K 0.52 1.589 rs1800120 G/T R1162L 0.00 2.038 rs1800123 C/T T1220I 0.22 0.059 rs34911792 T/G S1235R 0.45 1.483 rs11971167 G/A D1270N 0.12 1.739 rs4148725 C/T R1453W 0.00 2.513 Highly deleterious by SIFT and damaging by PolyPhen are indicated as bold deleterious in causing an effect in the structure and function of the protein by SIFT, PolyPhen and Pupasuite correlated well with experimental studies (Tsui 1992; Ghanem et al. 1994; Bienvenu et al. 1998) (Table 3). Login to comment 135 ABCC7 p.Phe508Cys According to this, the mutation occurred for native protein (1nbd) at position F508C with an SNP id namely (rs1800093), based on SIFT and PolyPhen results. Login to comment 138 ABCC7 p.Phe508Cys It can be seen that total energy for the native (1nbd) and mutant type structure F508C were found to be - 9786.37 and -9902.49 Kcal/mol respectively. Login to comment 140 ABCC7 p.Phe508Cys The superimposed structures of the native (1nbd) with mutant type protein F508C are shown in Figs. Login to comment 144 ABCC7 p.Phe508Cys It is interesting to note that the residues Ser (434), Tyr (512) and Ser (557) showed a change in solvent accessibility from a buried to exposed state and Ala (566) from an exposed to buried state in the mutant protein F508C. Login to comment 157 ABCC7 p.Phe508Cys Interestingly, on mutation at position F508C two residues, namely Leu (453) and Cys (491), in the native protein were replaced with the residues Glu (542) and Gly (543), respectively. Login to comment 177 ABCC7 p.Phe508Cys We mapped the deleterious mutation for (1nbd) at position F508C with an SNP id (rs1800093) based on SIFT and PolyPhen results. Login to comment 178 ABCC7 p.Phe508Cys Structural significance of native and mutant models of the CFTR gene at position F508C were further investigated in this work by solvent accessibility, secondary structure analysis and stabilizing residues. Login to comment