ABCMdb

ABCC2 p.Arg1066*

None has been submitted yet.

Publications

PMID: 16086317 [PubMed] Miksch S et al: "Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6."

No. Sentence Comment

292 R1030X in ABCC6, and R1066X in ABCC2 map to conserved arginyl residues among both genes within the first cytoplasmic loop of the third transmembrane domain. Login to comment

PMID: 10355502 [PubMed] Kamisako T et al: "Molecular aspects of organic compound transport across the plasma membrane of hepatocytes."

No. Sentence Comment

72 Studies carried out using antibodies raised against the C-terminal of MRP2 failed to demonstrate the presence of MRP2 in the canalicular membrane of a patient with Dubin-Johnson syndrome, suggesting that the lack of MRP2 is the cause of this syndrome.46 Recently, various gene abnormalities have been reported in a patient with Dubin-Johnson syndrome: a R768W, R1066X and splicing abnormality (1669del147) each in a homozygote, and a compound heterozygote with R768W and 2272del168.50,51 Bile acid transport In the early 1980s, potential-dependent transport in the canalicular membrane was reported to be involved in bile acid excretion from hepatocytes into bile.52 However,the physiological membrane potential (-35--40 mV) in hepatocytes is not high enough to create a concentration gradient between blood and bile (100-1000-fold difference required). Login to comment

PMID: 21044052 [PubMed] Pacifico L et al: "Mutational analysis of ABCC2 gene in two siblings with neonatal-onset Dubin Johnson syndrome."

No. Sentence Comment

27 Mutation analysis showed that both siblings were compound heterozygous for missense mutation on exon 18: p.R768W (c.2302 C>T) and nonsense mutation on exon 23 p.R1066X (c.3196 C>T). Login to comment
28 The study of allelic segregation in Letter to the Editor R100X R393W IVS6_IVS7del L441M IVS13 +2 T>A IVS15 +2 T>C G676R IVS18 +2 T>C R768W * 2748_2883del * R1066X * 3399_3400del L1173F 3615_3843del* Y1275X * R1310X Q1382R R1392_M1393del S325X W709R T1273A IVS8 +4 A>G 1256_1272delins CT 4292_4293delR1150H E1352Q * Exon 1 32 Fig. 1. Login to comment
45 The nonsense mutation p.R1066X is known in DJS and leads to the absence of four membrane-spanning domains and the complete second ATP cassette. Login to comment

PMID: 20082599 [PubMed] Jemnitz K et al: "ABCC2/Abcc2: a multispecific transporter with dominant excretory functions."

No. Sentence Comment

113 Among these mutations recently compiled by Nies and Keppler (2007), of the five amino acids affected that are located outside the nucleotide-binding domains, four are basic (R100X, R393W, R1066X, and R1150H) and one is neutral (I1173F). Login to comment
116 For the R100X, R393W, and R1066X, in vitro expression and analysis needs to be carried out to explore if functional activity is affected by the mutation. Login to comment

PMID: 16952291 [PubMed] Corpechot C et al: "Identification of a novel 974C-->G nonsense mutation of the MRP2/ABCC2 gene in a patient with Dubin-Johnson syndrome and analysis of the effects of rifampicin and ursodeoxycholic acid on serum bilirubin and bile acids."

No. Sentence Comment

78 Mutations in the MRP2/ABCC2 Gene Associated with DJS Nucleotide Mutation Exon Predicted Effect Reference 298C→T 3 R100X 27 974C→G 8 S325X This article IVS8 + 4A→G Intron 8 Aberrant splicing 28 1177C→T 9 R393W 29 1256insCT/ delAAACAG TGAACCT- GATG 10 Frameshift 30 1271A→G 10 R412G 31 1815 + 2T→A 13 Skipped exon 32, 33 1967 + 2T→C 15 Skipped exon 34, 35 2026G→C 16 G676R 35 2125T→C 17 W709R 36 2302C→T 18 R768W 32, 37, 38 2439 + 2T→C 18 Skipped exon 32, 35, 37 3196C→T 23 R1066X 39, 40 3449G→A 25 R1150H 41 3517A→T 25 I1173F 41 3928C→T 28 R1310X 27, 33 4145A→G 29 Q1382R 37 4175delGGATGA 30 R1392 + M1393 deletion 40 4292delCA 30 Frameshift 30 DISCUSSION Identification of a Novel Nonsense Mutation of the MRP2/ABCC2 Gene Up to now, 18 mutations in the sequence of the MRP2/ABCC2 gene have been reported in DJS, including nonsense mutations, deletions, splicing junction mutations, and missense mutations (Table 1). Login to comment

PMID: 16377077 [PubMed] Wada M et al: "Single nucleotide polymorphisms in ABCC2 and ABCB1 genes and their clinical impact in physiology and drug response."

No. Sentence Comment

41 In Japan, the expected number of Table 1 Summary of mutations identified in Dubin-Johnson syndrome (DJS) Mutation Exon IVS Amino acid alteration Reference 298COT 3 R100X a,b 1815C 2TOA 13 Exon13 skip [38] 1967C 2TOC 15 Exon15 skip [62] 2026GOC 16 G676R [92] 2302COT 18 R768W [49,91]c 2439C 2TOC 18 Exon18 skip [38]a,c 3196COT 23 R1066X [47] 3449GOA 25 R1150H [52] 3517AOT 25 I1173F [52] 3928COT 28 R1310X [50] 4145AOG 29 Q1382R [38] 4175- 4180del 30 RM1392-1393del [48] a Adachi and Wada, unpublished data. b Houkibara and Wada, unpublished data. Login to comment

PMID: 12884082 [PubMed] Wakusawa S et al: "Identification of a novel 2026G-->C mutation of the MRP2 gene in a Japanese patient with Dubin-Johnson syndrome."

No. Sentence Comment

43 With respect to the polymorphism )24C fi T, we also employed a restriction enzyme assay with BbsI; the results showed that his spouse and one daughter were heterozygous for this SNP, but other Table 1 Mutations of MRP2 in Dubin-Johnson syndrome (DJS) Nucleotide mutation Predicted effects References Splice site mutation 1815+2T fi A 1669del147 (exon13 skipping) Wada et al. 1998 1967+2T fi C 1901del67 (exon15 skipping) Kajihara et al. 1998 2439+2T fi C 2272del168 (exon18 skipping) Toh et al. 1999 Deletion mutation Del4170-5 Del R1392 , M1393 Tsujii et al. 1999 Missense mutation 2302C fi T R768 W Wada et al. 1998 3449G fi A R1150H Mor-Cohen et al. 2001 3517A fi T I1173F Mor-Cohen et al. 2001 4145A fi G Q1382R Toh et al. 1999 Nonesense mutation 3196C fi T R1066X Paulusma et al. 1997 3928C fi T R1310X Tate et al. 2002 family members did not possess it (Fig. 4). Login to comment