ABCMdb

PMID: 15167703

Lang T, Hitzl M, Burk O, Mornhinweg E, Keil A, Kerb R, Klein K, Zanger UM, Eichelbaum M, Fromm MF
Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver.
Pharmacogenetics. 2004 Mar;14(3):155-64., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC3 p.Ser346Phe ABCC3 p.Gly1423Arg ABCC3 p.Gln513Lys ABCC3 p.His68Tyr ABCC3 p.Arg1297His ABCC3 p.Lys13Asn SNPs 39G>C (allele frequency: 0.5%, located in exon 1), 202C>T (1.6%, exon 2), 1037C>T (0.5%, exon 9), 1537C>A (0.5%, exon 12), 3890G>A (5.2%, exon 27) and 4267G>A (0.6%, exon 29) resulted in Lys13Asn, His68Tyr, Ser346Phe, Gln513Lys, Arg1297His and Gly1423Arg amino acid substitutions, respectively. Login to comment 75 ABCC3 p.Ser346Phe ABCC3 p.His68Tyr ABCC3 p.Lys13Asn Six mutations located in exon 1 (39G.C; Lys13Asn; allele frequency: 0.5%), exon 2 (202C.T; His68Tyr; 1.6%), exon 9 (1037C.T; Ser346Phe; 0.5%), exon 12 (1537C. Login to comment 76 ABCC3 p.Gly1423Arg ABCC3 p.Gln513Lys ABCC3 p.Arg1297His A; Gln513Lys; 0.5%), exon 27 (3890G.A; Arg1297His; 5.2%) and exon 29 (4267G.A; Gly1423Arg; 0.6%) resulted in amino acid substitutions (Fig. 1). Login to comment 78 ABCC3 p.Arg1297His The most frequent amino acid exchange from Arg to His at position 1297 is located near the functionally important second ATP-binding domain (1323-1330). Login to comment 100 ABCC3 p.Ser346Phe ABCC3 p.Gly1423Arg ABCC3 p.Gln513Lys ABCC3 p.His68Tyr ABCC3 p.Arg1297His ABCC3 p.Lys13Asn Table 2 Polymorphisms identified in the MRP3 gene and frequencies of MRP3 mutations estimated among 103 Caucasian individuals Frequency (%) SNP ID 5` Sequence Genetic variation 3` Sequence Region Effect Alleles n Heterozygous Homozygous NCBI SNP ID 1 GAAGCCGGTG À1942G.T GTAGACAAGG Promoter 186 2.2, 0.4-6.6 (2.2) 0.0, 0.0-3.2 (0.0) 2 AGTCCCAGAG À1767G.A CATCAAGGAG Promoter 186 22.6, 15.7-30.9 (21.7) 1.1, 0.1-5.0 (1.5) rs1989983 3 GAGGTGGCTT À1328G.A CCCCTTCTGC Promoter 190 12.6, 7.5-19.7 (11.8) 0, 0.0-3.1 (0.4) 4 GGCTCCCACC À1298C.G ACACCTGCCG Promoter 192 2.1, 0.4-6.4 (2.1) 0, 0.0-3.1 (0.0) 5 TGAAACTGGA À1213C.G AGACCTGTGG Promoter 184 21.7, 14.9-30.0 (21.1) 1.1, 0.1-5.1 (1.4) 6 CCCCAACAAG À1134C.T GGTGCTGAGT Promoter 190 4.2, 1.5-9.4 (4.1) 0.0, 0.0-3.1 (0.0) rs4148403 7 ACCTGTCCTT À897delC CCCCCCCAAC Promoter 196 45.9, 37.3-54.7 (43.7) 9.2, 4.9-15.5 (10.3) rs4148404 8 CAGAGGGAAT À860T.G CACACATGTT Promoter 188 1.1, 0.1-4.9 (1.1) 0.0, 0.0-3.1 (0.0) 9 TCCCCCTGGC À260T.A TGGCCCAGGG Promoter 180 23.9, 16.8-32.4 (20.9) 1.1, 0.1-5.1 (1.6) 10 AGGGCCCCCC À211C.T ACCTCTGCCC Promoter 198 58.6, 49.8-67.0 (50.0) 21.2, 13.8-28.0 (24.5) rs4793665 11 TGGGTCCGAC À35C.A GCGCTCGCCT Exon 1 non-coding 196 1.0, 0.1-4.7 (1.0) 0.0, 0.0-3.0 (0.0) 12 TCGGCTCCAA 39G.C TTCTGGGTAA Exon 1 K13N 198 1.0, 0.1-4.7 (1.0) 0.0, 0.0-3.0 (0.0) 13 TTCTCTGTGT 46-6C.T CCCAGGACTC Intron 1 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 14 ACCTGTGGGT 141C.T GCCCTGCCCT Exon 2 silent 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 15 CATCCTCTCC 202C.T ACCTGTCCAA Exon 2 H68Y 192 3.1, 0.9-7.9 (3.1) 0.0, 0.0-3.1 (0.0) 16 CCAACCTGTG 223-12C.T TCTCTTCGCA Intron 2 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 17 GGGAAGAAGA 349-102A.C GGGGGTGGCC Intron 3 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 18 GGGGTGGCCC 349-90C.T AGAAACTTCT Intron 3 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 19 GAGAAATGGA 349-53G.A GCAGGTCCAG Intron 3 196 5.1, 2.0-10.4 (5.0) 0.0, 0.0-3.0 (0.1) rs2301836 20 CAGCCCCCAA 612þ73C.A CCCTCCAGTT Intron 5 166 10.8, 5.8-18.2 (10.2) 0.0, 0.0-3.5 (0.2) 21 TGATTCCCCC 613-22G.A TCCTATTCTC Intron 5 168 45.2, 36.0-54.8 (40.8) 6.0, 2.4-12.1 (8.2) rs739923 22 ACCCACTGCT 807-18C.T CTTCCTCCCT Intron 7 176 12.5, 7.2-19.8 (13.6) 1.1, 0.1-5.3 (0.6) rs2301837 23 TCCACACTCC 998þ16G.A GCTCACTATA Intron 8 154 7.8, 3.4-14.8 (7.5) 0.0, 0.0-3.8 (0.1) 24 ATGGCCCCCT 1037C.T CTGGTGGGGC Exon 9 S346F 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 25 TGCTTCCTGC 1339-107C.G CATCTACACA Intron 10 170 1.2, 0.1-5.5 (1.2) 0.0, 0.0-3.5 (0.0) 26 TGCCTCCTCA 1339-1G.T AACCTAGGTC Intron 10/Exon 11 splice site 174 1.1, 0.1-5.3 (1.1) 0.0, 0.0-3.4 (0.0) 27 TGAAGCTGTA 1512C.T GCCTGGGAGC Exon 12 silent 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 28 CTTCCTGAAG 1537C.A AGGTGGAGGG Exon 12 Q513K 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 29 GGAGGGCATC 1552A.C GGCAGGGTGA Exon 12 silent 202 6.9, 3.3-12.6 (6.7) 0.0, 0.0-2.9 (0.1) 30 CTTCCTGGTG 1635þ4delA GGCTTGGCAC Intron 12 splice site consenus 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 31 TGCTGGACGC 1695C.T GAGAAGGCCT Exon 13 silent 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 32 GTCCTCCTTT 1871-79C.T CCCTGCCCCC Intron 14 202 23.8, 17.0-31.8 (22.5) 75.2, 67.2-82.2 (75.8) rs879459 33 TTCCCTGCCC 1871-70C.G CCAGCCTCCC Intron 14 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 34 CTCCCTGACC 1871-22C.G TGCCCACCTT Intron 14 202 2.0, 0.4-6.1 (2.0) 0.0, 0.0-2.9 (0.0) 35 ACCTGCCCCC 1926C.A ACTCTGCACA Exon 15 silent 202 3.0, 0.8-7.5 (3.0) 0.0, 0.0-2.9 (0.0) 36 AGATTGGAGA 2238G.A AAGGTACAGA Exon 17 silent 166 1.2, 0.1-5.6 (1.2) 0.0, 0.0-3.5 (0.0) 37 AAGAGGCTAG 2241þ34G.C GCATAGAGCT Intron 17 166 41.0, 31.8-50.6 (42,0) 49.4, 39.9-58.9 (48.8) 38 TTCACACATT 2241þ97G.A GTGTAACGTT Intron 17 160 6.3, 2.5-12.7 (6.7) 1.3, 0.1-5.8 (0.3) 39 CCTTTCAATC 2600-123C.T CCCTCATTTT Intron 19 196 55.1, 46.3-63.7 (47.4) 11.2, 6.4-17.9 (15.0) rs4148415 40 CCAGCCCTCC 2714þ29C.T GGAGGCTGTA Intron 20 196 52.0, 43.3-60.7 (46.7) 11.2, 6.4-17.9 (13.9) rs2072365 41 GGCCTCCCCA 2714þ53A.G GCCCTGCCAG Intron 20 196 46.9, 38.3-55.7 (43.3) 8.2, 4.1-14.2 (10.0) rs2072366 42 TGAGGCTGGG 3039C.T GTCTATGCTG Exon 22 silent 156 10.3, 5.2-17.7 (12.1) 1.3, 0.1-5.9 (0.4) rs4148416 43 CCCCCCAAAC 3067þ71C.T GTGCCCTTGC Intron 22 180 20.0, 13.3-28.2 (19.8) 1.1, 0.1-5.2 (1.2) 44 TTATTGGGGC 3378þ47G.A GGGCAACACA Intron 23 202 11.9, 7.0-18.5 (11.2) 0.0, 0.0-2.9 (0.4) 45 ACACATGGGC 3378þ63G.T GGGGCAGCAG Intron 23 202 3.0, 0.8-7.5 (3.0) 0.0, 0.0-2.9 (0.0) 46 TCCCTCCTTT 3579-66C.T CCCTAAGCAG Intron 24 196 10.2, 5.6-16.7 (9.7) 0.0, 0.0-3.0 (0.3) rs967935 47 TATTCTGTGC 3890G.A CTACCGGCCG Exon 27 R1297H 192 10.4, 5.8-17.0 (9.9) 0.0, 0.0-3.1 (0.3) 48 TGCATGTGCA 3942C.T GGTGGCGAGA Exon 27 silent 192 30.2, 22.5-38.8 (31.1) 4.2, 1.4-9.3 (3.8) rs2277624 49 AGGTACGCGT 3954þ9G.T GGGTAGGCGG Intron 27 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 50 CTCAGAGGGC 4267G.A GGGAGAATCT Exon 29 G1423R 180 1.1, 0.1-5.2 (1.1) 0.0, 0.0-3.3 (0.0) 51 TAGTAGCTGA 4509A.G TTTGATTCTC Exon 31 silent 176 22.7, 15.6-31.3 (21.9) 1.1, 0.1-5.3 (1.6) rs1051640 SNPs with the ID 6, 7, 19, 21, 22, 32, 39, 40, 41, 42, 46, 48 and 51 previously reported by Saito et al. [13]. Login to comment 104 ABCC3 p.Ser346Phe ABCC3 p.Gly1423Arg ABCC3 p.Gln513Lys ABCC3 p.His68Tyr ABCC3 p.Arg1297His ABCC3 p.Lys13Asn 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 16 75 117 163 205 226 269 333 393 447 478 595 624 646 689 748 804 867 905 954 1023 1127 1199 1236 1270 1319 1372 1427 1493546 K13N H68Y S346F Q513K R1297H G1423R splice site mutation SNPs: P Exon: H2N out membrane in TMDs ATP TMDs ATP COOH Fig. 1 MRP3 gene and predicted two-dimensional protein structure using the MRP3 protein topology of Swiss-Prot O15438. Login to comment 112 ABCC3 p.Arg1297His No significant correlation was found between MRP3 protein variants and protein expression level including the most frequent Arg1297His protein variant. Login to comment 150 ABCC3 p.His68Tyr ABCC3 p.Arg1297His mutation found in this study was the SNP 3890G.A in exon 27 (Arg1297His) with an allele frequency of 5.2%, followed by SNP 202C.T in exon 2 (His68Tyr) with an allele frequency of 1.6%. Login to comment 153 ABCC3 p.Arg1297His Arg1297His did not significantly alter MRP3 protein expression. Login to comment