ABCC7 p.Trp1282Gly
| ClinVar: |
c.3844T>G
,
p.Trp1282Gly
?
, not provided
c.3846G>A , p.Trp1282* D , Pathogenic c.3844T>C , p.Trp1282Arg ? , not provided |
| CF databases: |
c.3846G>A
,
p.Trp1282*
D
, CF-causing
c.3844T>G , p.Trp1282Gly (CFTR1) D , The mutation W1282G was detected by DGGE and direct sequencing in a patient from Brazil (Caucasian origin), she carries [delta]F508 on the other chromosome and he presents PI and mild lung disease. c.3844T>C , p.Trp1282Arg (CFTR1) ? , In exon 20 we have found one Russian patient with the mutation T3976C. This mutation creates an AciI site. This enzyme also cuts DNA with the A4002G polymorphism. The two can be distinguished based on the size of the products. c.3846G>T , p.Trp1282Cys (CFTR1) ? , Found by DGGE and DNA sequencing. (CF patient, genotype [delta]F508/W1282C) |
| Predicted by SNAP2: | A: D (85%), C: D (85%), D: D (95%), E: D (95%), F: D (80%), G: D (95%), H: D (95%), I: D (80%), K: D (95%), L: D (71%), M: D (85%), N: D (95%), P: D (95%), Q: D (95%), R: D (75%), S: D (95%), T: D (95%), V: D (80%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, Y: N, |
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[hide] Polymorphisms of MRP1 (ABCC1) and related ATP-depe... Pharmacogenet Genomics. 2005 Aug;15(8):523-33. Conseil G, Deeley RG, Cole SP
Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters.
Pharmacogenet Genomics. 2005 Aug;15(8):523-33., [PMID:16006996]
Abstract [show]
Genetic variations in drug metabolizing enzymes and targets are established determinants of adverse drug reactions and interactions, but less is known about the role of genetic polymorphisms in membrane transport proteins. MRP1 (ABCC1) is one of 13 polytopic membrane proteins that comprise the 'C' subfamily of the ATP-binding cassette (ABC) superfamily of transport proteins. MRP1 and related ABCC family members, including MRP2, 3, 4 and 5 (ABCC2, 3, 4 and 5), each have a distinctive pattern of tissue expression and substrate specificity. Together, these five transporters play important roles in the disposition and elimination of drugs and other organic anions, and in maintenance of blood-tissue barriers, as confirmed by enhanced chemosensitivity of respective knockout mice. Moreover, Mrp2 (Abcc2) deficient animals display mild conjugated hyperbilirubinemia, corresponding to a human condition known as Dubin-Johnson syndrome (DJS). Naturally occurring mutations in MRP/ABCC-related drug transporters have been reported, some of which are non-synonymous single nucleotide polymorphisms. The consequences of the resulting amino acid changes can sometimes be predicted from in vitro site-directed mutagenesis studies or from knowledge of mutations of analogous (conserved) residues in ABCC proteins that cause DJS, Pseudoxanthoma elasticum (ABCC6), cystic fibrosis (CFTR/ABCC7) or persistent hyperinsulinemic hypoglycemia of infancy (SUR1/ABCC8). Continual updating of databases of sequence variants and haplotype analysis, together with in vitro biochemical validation assays and pharmacological studies in knockout animals, should make it possible to determine how genetic variation in the MRP-related transporters contributes to the range of responses to drugs and chemicals observed in different human populations.
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No. Sentence Comment
56 In the kidney, glomeruli and distal collecting tubules express MRP1, and, in the brain, MRP1 appears to form part of the drug permeability barrier Fig. 1 CF (CFTR/ABCC7) Q1291R E1228G Q1238R G1244E/V G1247R G1249R S1251N S1255P/L W1282G/R/C R1283K/M N1303K Y1307C E1321Q K1351E Q1352H R1268Q V1298F T1301I G1302R A1303P R1314W/Q G1321S R1339C Q1347H I1350L G1354R D1361N Q1382R A1450T R1347E R1351P V1359G/M S1368A G1377R G1382S R1392H R1419C R1435Q G1477R G1479R R1492W E1505K DJS (MRP2/ABCC2) NBD1 NBD2 COOH MEMBRANE MSD MSD MSD 12131415161710116 7 8 91 23 4 5TM H2 N Extracellular Intracellular PXE (ABCC6) PHHI (SUR1/ABCC8) Two-dimensional structure of MRP-related proteins.
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ABCC7 p.Trp1282Gly 16006996:56:230
status: NEW[hide] Cystic fibrosis in a southern Brazilian population... Clin Genet. 2007 Sep;72(3):218-23. Faucz FR, Gimenez J, Ramos MD, Pereira-Ferrari L, Estivill X, Raskin S, Casals T, Culpi L
Cystic fibrosis in a southern Brazilian population: characteristics of 90% of the alleles.
Clin Genet. 2007 Sep;72(3):218-23., [PMID:17718859]
Abstract [show]
Cystic fibrosis (CF) is a genetic disease that frequently leads to death in infancy among Europeans and their descendants. The goals of the present study were to analyze the molecular aspects of CFTR gene characterizing mutations, their frequencies, and the haplotypes formed by four CFTR gene intragenic markers, IVS8-6(T)n, IVS8CA, IVS17bTA and IVS17bCA, in a southern Brazilian population of Caucasian origin. DNA samples from 56 non-related CF patients were analyzed using scanning techniques (single strand conformation polymorphism and denaturing gradient gel electrophoresis), restriction fragment length polymorphism and direct DNA sequencing to identify the mutations. Our results revealed a total of 25 different CF mutations representing nearly 90% of CF alleles, two being novel mutations. Microsatellite haplotypes were defined for CF and normal alleles. The mutational spectrum and the associated haplotypes described for the first time in this study should prove relevant for genetic counselling and CF population screening in Brazil. Moreover, our results suggest the presence of a major Mediterranean component in the contemporary Brazilian CF patient pool.
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No. Sentence Comment
61 One was detected by DGGE analysis and direct sequencing of exon 20 showing a substitution of T to G at nucleotide 3976, named W1282G, (p.Trp1282Gly).
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ABCC7 p.Trp1282Gly 17718859:61:126
status: NEWX
ABCC7 p.Trp1282Gly 17718859:61:137
status: NEW80 Mutations G85E, R334W, R553X, 62111G.A, 1717-8G.A, G1069R and W1282G were associated with haplotypes not observed in the normal CFTR genes.
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ABCC7 p.Trp1282Gly 17718859:80:62
status: NEW85 In addition, 16 other mutations were characterized, including two novel mutations, W1282G and 232del18.
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ABCC7 p.Trp1282Gly 17718859:85:83
status: NEW[hide] Improvement in clinical markers in CF patients usi... J Cyst Fibros. 2008 Sep;7(5):433-6. Epub 2008 May 21. Visca A, Bishop CT, Hilton SC, Hudson VM
Improvement in clinical markers in CF patients using a reduced glutathione regimen: an uncontrolled, observational study.
J Cyst Fibros. 2008 Sep;7(5):433-6. Epub 2008 May 21., [PMID:18499536]
Abstract [show]
CFTR mutation, which causes cystic fibrosis (CF), has also recently been identified as causing glutathione system dysfunction and systemic deficiency of reduced glutathione (GSH). Such dysfunction and deficiency regarding GSH may contribute to the pathophysiology of CF. We followed 13 patients (age range 1-27 years) with cystic fibrosis who were using a regimen of reduced glutathione (GSH), including oral glutathione and inhaled buffered glutathione in an uncontrolled, observational study. Dosage ranged from 66-148 mg/kg/day in divided doses, and the term examined was the initial 5.5 months of GSH use (45 days of incrementally adjusted dose, plus 4 months of use at full dosage). Baseline and post-measurements of FEV1 percent predicted, BMI percentile, and weight percentile were noted, in addition to bacterial status and pulmonary exacerbations. Significant improvement in the following clinical parameters was observed: average improvement in FEV1 percent predicted (N=10) was 5.8 percentage points (p<0.0001), average weight percentile (N=13) increased 8.6 points (p<0.001), BMI percentile (N=11) improved on average 1.22 points (p<0.001). All patients improved in FEV1 and BMI, if measured in their case; 12 of 13 patients improved in weight percentile. Positive sputum cultures of bacteria in 11 patients declined from 13 to 5 (p<0.03) with sputum cultures of Pseudomonas aeruginosa becoming negative in 4 of 5 patients previously culturing PA, including two of three patients chronically infected with PA as determined by antibody status. Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies.
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No. Sentence Comment
43 65 64 71 28.5 28 30 9 5 6 PA PA none 3, F, 19 DF508/G1244E 47 48 55 43 43 48 3 3 9 PA b PAb PA 4, M, 5 DF508/R347P NA NA NA 17 17.5 19 33 33 40 SA SA none 5, M, 24 W1282G/G542X 60 58 70 51 51.5 57 3 3 7 BC BC BC 6, F, 14 3659delC/?
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ABCC7 p.Trp1282Gly 18499536:43:164
status: NEW64 15.1 15.3 1 0 36 30 3, F, 19 DF508/G1244E 16.3 18.3 0 0 9 18 4, M, 5 DF508/R347P 14.7 15.4 0 1 11 11 5, M, 24 W1282G/G542X 17.8 19.7 1 0 16 20 6, F, 14 3659delC/?
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ABCC7 p.Trp1282Gly 18499536:64:110
status: NEW