ABCMdb

ABCG2 p.Ser13Leu

Predicted by SNAP2:	A: D (66%), C: D (75%), D: D (75%), E: D (71%), F: D (85%), G: D (75%), H: D (80%), I: D (80%), K: D (75%), L: D (80%), M: D (71%), N: D (66%), P: D (80%), Q: D (63%), R: D (80%), T: D (63%), V: D (80%), W: D (91%), Y: D (85%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, T: N, V: N, W: D, Y: N,

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Publications
[hide] Genetic variation and haplotype structure of the A... Drug Metab Pharmacokinet. 2006 Apr;21(2):109-21. Maekawa K, Itoda M, Sai K, Saito Y, Kaniwa N, Shirao K, Hamaguchi T, Kunitoh H, Yamamoto N, Tamura T, Minami H, Kubota K, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Ozawa S, Sawada J
Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population.
Drug Metab Pharmacokinet. 2006 Apr;21(2):109-21., [PMID:16702730]

Abstract [show]
The ATP-binding cassette transporter, ABCG2, which is expressed at high levels in the intestine and liver, functions as an efflux transporter for many drugs, including clinically used anticancer agents such as topotecan and the active metabolite of irinotecan (SN-38). In this study, to elucidate the linkage disequilibrium (LD) profiles and haplotype structures of ABCG2, we have comprehensively searched for genetic variations in the putative promoter region, all the exons, and their flanking introns of ABCG2 from 177 Japanese cancer patients treated with irinotecan. Forty-three genetic variations, including 11 novel ones, were found: 5 in the 5'-flanking region, 13 in the coding exons, and 25 in the introns. In addition to 9 previously reported nonsynonymous single nucleotide polymorphisms (SNPs), 2 novel nonsynonymous SNPs, 38C>T (Ser13Leu) and 1060G>A (Gly354Arg), were found with minor allele frequencies of 0.3%. Based on the LD profiles between the SNPs and the estimated past recombination events, the region analyzed was divided into three blocks (Block -1, 1, and 2), each of which spans at least 0.2 kb, 46 kb, and 13 kb and contains 2, 24, and 17 variations, respectively. The two, eight, and five common haplotypes detected in 10 or more patients accounted for most (>90%) of the haplotypes inferred in Block -1, Block 1, and Block 2, respectively. The SNP and haplotype distributions in Japanese were different from those reported previously in Caucasians. This study provides fundamental information for the pharmacogenetic studies investigating the relationship between the genetic variations in ABCG2 and pharmacokinetic/pharmacodynamic parameters.

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No. Sentence Comment
10 In addition to 9 previously reported nonsynonymous single nucleotide polymorphisms (SNPs), 2 novel nonsynonymous SNPs, 38CÀT (Ser13Leu) and 1060GÀA (Gly354Arg), were found with minor allele frequencies of 0.3z. Login to comment
73 Two novel nonsynonymous SNPs, 38CÀT (Ser13Leu) and 1060GÀA (Gly354Arg), were heterozygous in dierent patients at an allele frequency of 0.003. Login to comment
130 In Block 1, seven haplotype groups (*1 to *7) were inferred, and the groups of *2 to *7 harbored non-synonymous SNPs, 421CÀA (Gln141Lys) (*2), 34GÀA (Val12Met) (*3), 376CÀT (Gln126X) (*4), 38CÀT (Ser13Leu) (*5), 479GÀA (Arg160Gln) (*6), and 1060GÀA (Gly354Arg) (*7). Login to comment
152 Eleven nonsynonymous variations, including two novel ones (Ser13Leu and Gly354Arg), were found. Login to comment
158 The functional eects of the other ve nonsynonymous SNPs (Ser13Leu, Arg160Gln, Gly354Arg, Phe431Leu, and Phe489Leu) have not yet been characterized. Login to comment
159 Using the PolyPhen program (http:WW www.bork.embl-heidelberg.deWPolyPhenW) to predict the functional eect of these amino acid substitutions, three substitutions, Ser13Leu, Arg160Gln, and Gly354Arg, were estimated to cause possible alterations in protein function based on the PSIC (position specic independent count) prole score. Login to comment