ABCMdb

ABCB11 p.Arg1231Gln

None has been submitted yet.

Publications

PMID: 15317749 [PubMed] Alvarez L et al: "Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1."

No. Sentence Comment

44 A, R1231Q) in ABCB11 and lacked immunohistochemically demonstrable BSEP at canaliculi; MRP2 marked normally (Fig. 2). Login to comment
42 A, R1231Q) in ABCB11 and lacked immunohistochemically demonstrable BSEP at canaliculi; MRP2 marked normally (Fig. 2). Login to comment

PMID: 19101985 [PubMed] Byrne JA et al: "Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing."

No. Sentence Comment

100 No spliced ABCB11 PCR product was generated for the nucleotide changes associated with T586I (c.1757CϾT; 0%; Fig. 2D) and R1231Q (c.3692GϾA; 0%; Fig. 2F). Login to comment
154 The following mutations showed an enrichment of mature BSEP: R1153H (c.3458GϾA; Fig. 6B), R1128C (c.3382CϾT), R1128H (c.3383GϾA), R1231Q (c.3692GϾA), R1050C (c.3148CϾT; Fig. 6C) and R1268Q (c.3892GϾA), A570T (c.1708GϾA), and E297K (c.889GϾA; Fig. 6D). Login to comment
219 These include the PFIC-associated mutations E297G (c.890AϾG; Fig. 6A), R1128C (c.3382CϾT) and R1231Q (c.3692GϾA; Fig. 6C), and R1268Q (c.3892GϾA; Fig. 6.d), the BRIC-associated mutations R1128H (c.3383GϾA) and R1050C (c.3148CϾT; Fig. 6C), and E297K (c.889GϾA; Fig. 6D), as well as A570T (c.1708GϾA), which can be associated with either form of disease. Login to comment

PMID: 21490445 [PubMed] Evason K et al: "Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies."

No. Sentence Comment

143 Immunohistochemical Findings and Genetic Abnormalities Patient BSEP Mutation Type of Mutation(s) 1 Absent c.890A>G (p.E297G)* Missense5,7,10,13,16,19,20 2 Absent c.1723C>T (p.R575X) Nonsense7,19,20 c.2178+1G>T Noncoding region20 3 Present c.1708G>A (p.A570T) Missense20 c.3634G>T (p.V1212F) Missense, predicted deleterious 4 Absent c.3164T>C (p.L1055P)* Missense, predicted deleterious 5 Absent c.3692G>A (p.R1231Q) Missense20 c.2296G>A (p.G766R) Missense20 6 Absent c.2782C>T (p.R928X) Nonsense13 c.3268C>T (p.R1090X) Nonsense5,7,13 7 Present c.3347G>A (p.G1116E) Missense, predicted deleterious IVS 23-8 G-A Noncoding region 8 Absent IVS 16-8 T>Gw Noncoding region10 9 Absent c.2944G>A (p.G982R) Missense5,7,19,20 c.2296G>A (p.G766R) Missense20 10 Absent c.2944G>A (p.G982R) Missense5,7,19,20 c.2296G>A (p.G766R) Missense20 11 Absent c.319T>C (p.C107R) Missense, predicted deleterious c.611+4A>G Noncoding region 12 Absent c.1723C>T (p.R575X) Nonsense7,19,20 c.2178+1G>T Noncoding region20 *Homozygous. Login to comment

PMID: 18395098 [PubMed] Strautnieks SS et al: "Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families."

No. Sentence Comment

150 Missense Mutations in ABCB11 Nucleotide change Predicted effect Exon CpG site Location Change in: Size Charge Hyd/Pol Shape c.149Tb0e;C p.Leu50Ser 4 No NH2 term Y Y Y c.470Ab0e;G p.Tyr157Cys 6 No TM2 Y Y Y c.725Cb0e;T p.Thr242Ile 8 No TM4 Y Y c.890Ab0e;G p.Glu297Gly 9 No IC2 Y Y Y c.908Gb0e;A p.Arg303Lys 9 No IC2 c.937Cb0e;A p.Arg313Ser 10 Yes IC2 Y Y Y Y c.980Gb0e;A p.Gly327Glu 10 No TM5 Y Y Y c.1168Gb0e;C p.Ala390Pro 11 No TM/NBF Y c.1229Gb0e;A p.Gly410Asp 12 No TM/NBF Y Y c.1238Tb0e;G p.Leu413Trp 12 No TM/NBF c.1388Cb0e;T p.Thr463Ile 13 No Adj Walker A Y Y Y c.1396Cb0e;A p.Gln466Lys 13 No Adj Walker A Y c.1409Gb0e;A p.Arg470Gln 13 Yes Adj Walker A Y c.1415Ab0e;G p.Tyr472Cys 13 No Adj Walker A Y Y Y c.1442Tb0e;A p.Val481Glu 14 No NBF1 Y Y Y c.1445Ab0e;G p.Asp482Gly 14 No NBF1 Y Y c.1460Gb0e;C p.Arg487Pro 14 Yes NBF1 Y Y Y Y c.1468Ab0e;G p.Asn490Asp 14 No NBF1 Y c.1535Tb0e;C p.Ile512Thr 14 No NBF1 Y Y Y c.1544Ab0e;C p.Asn515Thr 14 No NBF1 Y Y c.1550Gb0e;A p.Arg517His 14 Yes NBF1 Y Y c.1621Ab0e;C p.Ile541Leu 14 No NBF1 c.1622Tb0e;C p.Ile541Thr 14 No NBF1 Y Y Y c.1643Tb0e;A p.Phe548Tyr 15 No Adj ABC c.1685Gb0e;A p.Gly562Asp 15 No ABC Y Y c.1708Gb0e;A p.Ala570Thr 15 Yes ABC/Walker B Y c.1763Cb0e;T p.Ala588Val 15 No Adj Walker B Y c.2272Gb0e;C p.Gly758Arg 19 No NBF/TM Y Y Y c.2296Gb0e;A p.Gly766Arg 19 Yes TM7 Y Y Y c.2494Cb0e;T p.Arg832Cys 21 Yes IC3 Y Y Y Y c.2576Cb0e;G p.Thr859Arg 21 No IC3 Y Y Y Y c.2842Cb0e;T p.Arg948Cys 23 Yes IC4 Y Y Y Y c.2935Ab0e;G p.Asn979Asp 23 No TM11 Y c.2944Gb0e;A p.Gly982Arg 23 Yes TM11 Y Y Y c.3086Cb0e;A p.Thr1029Lys 24 No TM12 Y Y Y Y c.3329Cb0e;A p.Ala1110Glu 25 Yes Adj Walker A Y Y Y c.3382Cb0e;T p.Arg1128Cys 25 Yes Adj Walker A Y Y Y Y c.3457Cb0e;T p.Arg1153Cys 26 Yes NBF2 Y Y Y Y c.3458Gb0e;A p.Arg1153His 26 Yes NBF2 Y Y c.3460Tb0e;C p.Ser1154Pro 26 No NBF2 Y c.3628Ab0e;C p.Thr1210Pro 27 No Adj ABC Y c.3691Cb0e;T p.Arg1231Trp 27 Yes ABC/Walker B Y Y c.3692Gb0e;A p.Arg1231Gln 27 Yes ABC/Walker B Y c.3724Cb0e;A p.Leu1242Ile 27 No Walker B c.3892Gb0e;A p.Gly1298Arg 28 No NBF2 Y Y Y NOTE. Login to comment

PMID: 22795478 [PubMed] Kubitz R et al: "The bile salt export pump (BSEP) in health and disease."

No. Sentence Comment

173 By the use of an in vitro minigene approach, interference with splicing was shown for c.1445A > G (p.D482G), c.1757C > T (p.T586I), c.3432C > A (p.S1144R), c.3458G > A (p.R1153H), c.3460T > C (p.S1154P), c.3691C > T (p.R1231 W) and c.3692G > A (p.R1231Q) [132]. Login to comment

PMID: 24530123 [PubMed] Naoi S et al: "Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2."

No. Sentence Comment

1 A homozygous c.3692G>A (p.R1231Q) mutation was identified in ABCB11. Login to comment
9 To test this hypothesis, we investigated the effects of 4PB therapy in a patient with PFIC2 carrying a homozygous c.3692G>A (p.R1231Q) mutation in ABCB11. Login to comment
22 She developed hepatocellular cholestasis and jaundice with normal serum gamma-glutamyl transferase (GGT) activity at the age of 2 months and was diagnosed with PFIC2 by the presence of the c.3692G>A (p.R1231Q) mutation in both alleles of ABCB11 and no detectable immunosignal for BSEP at the canalicular membrane of a liver section sample (Figure 1, A and B). Login to comment
28 In Vitro Studies pShuttle (Clontech, Palo Alto, California) containing complementary DNA (cDNA) of human BSEP with a hemagglutinin (HA) tag at the N-terminus (HA-BSEPwild type [WT] ) and that of HA-BSEPWT with the c.3692G>A (p.R1231Q) or p.T1210P mutation (HA-BSEPR1231Q and HA-BSEPT1210P ) were used for this study.8 The c.3692G>A (p.R1231Q) and p.T1210P mutations were introduced into pShuttle containing HA-BSEPWT cDNA by site-directed mutagenesis as described previously.9 HEK293T cells and McA-RH7777 cells transfected with pShuttle containing HA-BSEPWT , HA-BSEPR1231Q , or HA-BSEPT1210P cDNA, or empty vector (EV) (HA-BSEPWT , HA-BSEPR1231Q , HA-BSEPT1210P , or EV HEK293T cells and HA-BSEPWT , HA-BSEPR1231Q , HA-BSEPT1210P , or EV McA-RH7777 cells) were subjected to analysis of quantitative PCR (qPCR), cell surface biotinylation, immunofluorescence, and transport.Allinvitroexperiments were performed asdescribed previously,7,9 and a detailed description of the experiments is presented in the Appendix. Login to comment
48 The homozygous c.3692G>A (p.R1231Q) mutation in ABCB11 identified is shown by the arrowhead. Login to comment
56 HEK293T cells (top) and McA-RH7777 cells (bottom) expressing HA-BSEPWT (WT; left) or HA-BSEPR1231Q (R1231Q, right) were analyzed by confocal immunofluorescence microscopy as described in the Methods. Login to comment
64 Therefore, all encoding exons and flanking areas of both ATP8B1 and ABCB11 were sequenced, and a homozygous c.3692G>A (p.R1231Q) mutation in ABCB11 was identified, which has been reported previously in European white patients with PFIC2 (Figure 1, A).12 This result, combined with the immunosignal of ATP8B1, but not of BSEP at the canalicular membrane of liver sections (Figure 1, B), was the basis of the diagnosis of PFIC2. Login to comment
65 To characterize the effect of the c.3692G>A (p.R1231Q) mutation on BSEP, HA-BSEPWT and HA-BSEPR1231Q were expressed ectopically in HEK293T cells and McA-RH7777 cells, a rat hepatoma cell line that develops canalicular membranes through the formation of couplets as hepatocytes. Login to comment
79 These results suggest that 4PB treatment at a clinically relevant dosage for humans could increase BSEP expression at the canalicular membrane in patients with PFIC2 with the c.3692G>A (p.R1231Q) mutation in ABCB11 and, consequently, expand the capacity to secrete bile salt into bile. Login to comment
82 Therapeutic Effect of 4PB in the Patient with PFIC2 with the c.3692G>A (p.R1231Q) Mutation in ABCB11 Serum liver tests and the itching score did not improve during the period of 4PB treatment at the dosages of 200 and 350 mg/kg/day. However, the serum level of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) started to decrease when the dosage was increased to 500 mg/kg/day. Login to comment
97 HA-BSEPWT (WT) and HA-BSEPR1231Q (R1231Q) HEK293T cells were treated with or without 1 mM 4PB for 24 hour and subjected to A, qPCR and B, cell surface biotinylation and analyzed as described in Methods. Login to comment
99 McA-RH7777 cells expressing HA-BSEPWT (WT, left) or HA-BSEPR1231Q (R1231Q, right) were treated with or without 1 mM 4PB for 24 hours and then subjected to confocal immunofluorescence microscopy as described in Figure 1, E. Login to comment
136 Analysis using an in vitro minigene system has suggested that c.3692G>A (p.R1231Q) in ABCB11 causes aberrant ABCB11 splicing.22 However, because BSEP was detected around 160 kDa, which is identical to the value in the control patients (Figure 4, C) and to the reported molecular weight,9 it is likely that the correct splicing occurred to some degree in our patient despite having c.3692G>A (p.R1231Q) in ABCB11 and its resultant protein product on the canalicular membrane was prevented from degradation by 4PB therapy. Login to comment

PMID: 25027376 [PubMed] Kubitz R et al: "Genetic variations of bile salt transporters."

No. Sentence Comment

137 BSEP/Bsep NTCP ASBT Exon skipping E186G G1116R G319G R1128C T463I R1128H A926P E1186K A1028Aa R1231W A1110E Aberrant splicing E297K R1153H R832C S1154P S1144R No splice product T586I R1231Q Reduced plasma membrane expression E135K A570T I223T E297Gb N591Sb V444A R1050C Intracellular retention Y818F G982R Reduced or absent bile salt transport A570T R432T A64T K314E V98Ic M264V I206V Q558H I223T C144Y P290S E297Gb N591Sb S267F L243P G374S E1186K I279T T262M a A1028A induces significant exon skipping in vitro but probably not in vivo (unpublished data; Dro &#a8;ge, Ha &#a8;ussinger, Kubitz). Login to comment