ABCMdb

ABCC1 p.Asp1365Asn

Predicted by SNAP2:	A: D (59%), C: N (57%), E: N (66%), F: D (75%), G: D (71%), H: D (63%), I: D (75%), K: D (80%), L: D (75%), M: D (66%), N: D (63%), P: D (80%), Q: D (59%), R: D (75%), S: D (59%), T: N (72%), V: D (71%), W: D (80%), Y: D (71%),
Predicted by PROVEAN:	A: D, C: D, E: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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[hide] Genetic variation of the ABC transporter gene ABCC... BMC Genet. 2015 Sep 23;16(1):114. doi: 10.1186/s12863-015-0271-3. Slomka M, Sobalska-Kwapis M, Korycka-Machala M, Bartosz G, Dziadek J, Strapagiel D
Genetic variation of the ABC transporter gene ABCC1 (Multidrug resistance protein 1-MRP1) in the Polish population.
BMC Genet. 2015 Sep 23;16(1):114. doi: 10.1186/s12863-015-0271-3., [PMID:26395522]

Abstract [show]
BACKGROUND: Multidrug resistance-associated protein 1 (MRP1), encoded by the ABCC1 gene, is an ATP-binding cassette transporter mediating efflux of organic anions and xenobiotics; its overexpression leads to multidrug resistance. In this study, 30 exons (from 31 in total) of the ABCC1 gene as well as and their flanking intron sequences were screened for genetic variation, using the High Resolution Melting (HRM) method, for 190 healthy volunteers representing the Polish population. Polymorphism screening is an indispensable step in personalized patient therapy. An additional targeted SNP verification study for ten variants was performed to verify sensitivity of the scanning method. RESULTS: During scanning, 46 polymorphisms, including seven novel ones, were found: one in 3' UTR, 21 in exons (11 of them non-synonymous) and 24 in introns, including one deletion variant. These results revealed some ethnic differences in frequency of several polymorphisms when compared to literature data for other populations. Based on linkage disequilibrium analysis, 4 haplotype blocks were determined for 9 detected polymorphisms and 12 haplotypes were defined. To capture the common haplotypes, haplotype-tagging single nucleotide polymorphisms were identified. CONCLUSIONS: Targeted genotyping results correlated well with scanning results; thus, HRM is a suitable method to study genetic variation in this model. HRM is an efficient and sensitive method for scanning and genotyping polymorphic variants. Ethnic differences were found for frequency of some variants in the Polish population compared to others. Thus, this study may be useful for pharmacogenetics of drugs affected by MRP1-mediated efflux.

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138 Similarly, three variants changing amino acids in the loop containing NBD2 were detected: c.3886C > T (p.Arg1296Trp) and c.3901C > T (p.Arg1301Cys) are located 30 and 25 amino acids upstream of the Walker A motif, respectively, while c.4093G > A (p.Asp1365Asn) is located 30 amino acids downstream of the motif. Login to comment
140 Analysis of all the non-synonymous variants detected in this study by the PolyPhen-2 tool (data in Additional file 3) showed for HumDiv-trained model that five of them: c.814C > T (p.Pro272Ser), c.1898G > A (p.Arg633 Gln), c.2168G > A (p.Arg723Gln), c.2876A > G (p.Lys 959Arg), the novel one c.4093G > A (p.Asp1365Asn), probably have benign influence on the functioning of the protein. Login to comment
151 Small areas of low |D`| values, and hence weak or lacking of linkage, were defined between polymorphisms from group: c.225 + 26G > A, c.352-66 T > C, c.809 + 31G > T, c.809 + 54C > A, c.809 + 64C > G, c.816G > A, c.825 T > C, c.1062 T > C, c.1218 + 8A > G, c.1677 + 56C > T, and those from group: c.1678-37G > A, c.1684 T > C, Table 2 Summary of ABCC1 variants detected during scanning by HRM (Continued) 28 rs2230671 c.4002G > A p.Ser1334= 102 68 18 0.202 (A) 0.277 28 rs188980645 c.4093G > A p.Asp1365Asn 187 1 0 1 (A) 0.003 29 rs212087 c.4126-45G > A Intron 62 85 42 0.239 (A) 0.447 30 rs212088 c.4487 + 18G > A Intron 136 47 5 0.775 (A) 0.148 31 rs587783374* c.4551G > A p.Gln1517= 186 1 0 1 (A) 0.003 31 rs373453875 c. Login to comment