ABCB11 p.Glu636Gly
| Reviews: |
p.Glu636Gly
D
|
| Predicted by SNAP2: | A: D (75%), C: D (75%), D: D (85%), F: D (85%), G: D (91%), H: D (85%), I: D (85%), K: D (91%), L: D (91%), M: D (85%), N: D (91%), P: D (95%), Q: D (75%), R: D (91%), S: D (91%), T: D (85%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, 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] Bile salt export pump gene mutations in two Japane... J Pediatr Gastroenterol Nutr. 2003 May;36(5):647-50. Goto K, Sugiyama K, Sugiura T, Ando T, Mizutani F, Terabe K, Ban K, Togari H
Bile salt export pump gene mutations in two Japanese patients with progressive familial intrahepatic cholestasis.
J Pediatr Gastroenterol Nutr. 2003 May;36(5):647-50., [PMID:12717091]
Abstract [show]
BACKGROUND: In recent years, progressive familial intrahepatic cholestasis has been classified into at least three types by genetic analysis: PFIC1, PFIC2, and MDR3. Liver transplantation is effective for treating patients with this intractable syndrome. Confirming the correct diagnosis is of paramount importance because prognosis after transplantation differs with the genetic type of the disease. METHODS: Synthesis of cDNA was accomplished using RNA extracted from liver tissue of two Japanese patients with progressive familial intrahepatic cholestasis. Polymerase chain reaction was performed using 13 primer sets designed for amplification of the bile salt export pump cDNA. Direct sequencing was undertaken, and identified sequences were compared with the sequence for bile salt export pump gene registered with GenBank. In addition, gene sequences for nonprogressive familial intrahepatic cholestasis patients were analyzed. RESULTS: Genetic analysis of patient 1 revealed that substitutions in bile salt export pump protein sequences, namely R575X and E636G, might be the cause of the disease. In patient 2, V330X and R487H might fulfill the same role. Results of gene analysis in parents and cholestatic controls supported these conclusions. CONCLUSIONS: Absence or presence of bile salt export protein gene mutations was confirmed as representing a useful prognostic marker for clinical course after liver transplantation.
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No. Sentence Comment
72 Of the remaining three substitutions, two were also seen in some control subjects, whereas E636G was not seen in any of the control subjects. Results of genetic analyses performed on family members revealed that R575X was paternal in origin, whereas E636G was maternal in origin. None of these mutations were observed in the asymptomatic brother.
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ABCB11 p.Glu636Gly 12717091:72:91
status: NEWX
ABCB11 p.Glu636Gly 12717091:72:250
status: NEW82 Differences between BSEP mRNA sequence of Case 1 and registered sequence, and results of genetic analyses performed on family members Nucleotide number of reference sequence Nucleotide substitutions from reference sequence Type of nucleotide Amino acid substitutions from reference sequence Familial investigation of nucleotide substitutions Frequency of alleles of non-PFIC cases 1015 G → C G Val → Leu 0/10 homo C (V339L) 10/10 1331 T → C T Val → Ala 2/10 hetero C (V444A) 8/10 1723 C → T C Arg → Stop Patient: CT Father: CT 10/10 hetero T (R575X) Mother: CC Brother: CC 0/10 1907 A → G A Glu → Gly Patient: AG Father: AA 110/110 hetero G (E636G) Mother: AG Brother: AA 0/100 2594 C → T C Ala → Val 106/110 hetero T (A865V) 4/110 3084 A → G A (-) 5/10 homo G 5/10 A, adenine; T, thymine; G, guanine; C, cytosine; Val, V, valine; Leu, L, Leucine; Ala, A, alanine; Arg, R, arginine; Glu, E, glutamate; Gly, G, glycine; homo, homozygote; hetero, heterozygote.
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ABCB11 p.Glu636Gly 12717091:82:698
status: NEW86 The R575X mutation seen in patient 1 of the present study is a nonsense mutation in the first nucleotide binding fold of the BSEP protein, whereas the E636G mutation is a missense mutation located between the first nucleotide binding fold and the seventh transmembrane domain.
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ABCB11 p.Glu636Gly 12717091:86:151
status: NEW[hide] The bile salt export pump. Pflugers Arch. 2007 Feb;453(5):611-20. Epub 2006 Oct 19. Stieger B, Meier Y, Meier PJ
The bile salt export pump.
Pflugers Arch. 2007 Feb;453(5):611-20. Epub 2006 Oct 19., [PMID:17051391]
Abstract [show]
Canalicular secretion of bile salts mediated by the bile salt export pump Bsep constitutes the major driving force for the generation of bile flow. Bsep is a member of the B-family of the super family of ATP-binding cassette transporters and is classified as ABCB11. Bsep has a narrow substrate specificity, which is largely restricted to bile salts. Bsep is extensively regulated at the transcriptional and posttranscriptional level, which directly modulates canalicular bile formation. Pathophysiological alterations of Bsep by either inherited mutations or acquired processes such as inhibition by drugs or disease-related down regulation may lead to a wide spectrum of mild to severe forms of liver disease. Furthermore, many genetic variants of Bsep are known, some of which potentially render individuals susceptible to acquired forms of liver disease.
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160 Their bile flow rate is slightly but not significantly lower in comparison to controls, but the total bile salt output into bile is massively reduced and their liver bile salt concen- S114R G238V V284L* C336S D482G R487H S593R E636G G982R G1004D R1153CD R1268Q E186G E297G R432T I498T I498T T923P A926P R1050C R1128H S194P G260D N519S A1228V V444A K461E M677V R698H PFIC2 BRIC2 acquired cholestasis SNP Fig. 2 Putative secondary structure of Bsep (NT-005403) generated with the TOPO program (http://www.sacs.ucsf.edu/TOPO-run/wtopo.pl).
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ABCB11 p.Glu636Gly 17051391:160:227
status: NEW[hide] Prediction of drug-induced intrahepatic cholestasi... Expert Opin Drug Saf. 2007 Jan;6(1):71-86. Sakurai A, Kurata A, Onishi Y, Hirano H, Ishikawa T
Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump.
Expert Opin Drug Saf. 2007 Jan;6(1):71-86., [PMID:17181454]
Abstract [show]
Drug-induced intrahepatic cholestasis is one of the major causes of hepatotoxicity, which often occur during the drug discovery and development process. Human ATP-binding cassette transporter ABCB11 (sister of P-glycoprotein/bile salt export pump) mediates the elimination of cytotoxic bile salts from liver cells to bile, and, therefore, plays a critical role in the generation of bile flow. The authors have recently developed in vitro high-speed screening and quantitative structure-activity relationship analysis methods to investigate the interaction of ABCB11 with a variety of compounds. Based on the extent of inhibition of the bile salt export pump, the authors analysed the quantitative structure-activity relationship to identify chemical groups closely associated with the inhibition of ABCB11. This approach provides a new tool to predict compounds with a potential risk of drug-induced intrahepatic cholestasis.
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120 H2N COOH S56L G238V G260D C336S L339V V444A K461E D482G T923P K930X G982R R1090X R1153C Outside Inside R1268Q A1228VE1186K R1128H R1057X R1050C A926P A865V R698H E636G M677V S593R E592Q N591S R575XA570T Q558H I498T R432T R415Q R299K E297G V284A I206V S194P E186G cholestasis Expert Opin. Drug Saf. (2007) 6(1) Table 1.
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ABCB11 p.Glu636Gly 17181454:120:162
status: NEW124 [47] - 15 1907 A→G Glu636Gly PFIC2 [46] rs11568364 16 2029 A→G Met677Val - [39,41,44,102] - 16 2093 G→A Arg698His - [44] - 16 2098 A→del Frame shift at position 700 PFIC2?
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ABCB11 p.Glu636Gly 17181454:124:26
status: NEW[hide] Novel ABCB11 mutations in a Thai infant with progr... World J Gastroenterol. 2009 Sep 14;15(34):4339-42. Treepongkaruna S, Gaensan A, Pienvichit P, Luksan O, Knisely AS, Sornmayura P, Jirsa M
Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis.
World J Gastroenterol. 2009 Sep 14;15(34):4339-42., 2009-09-14 [PMID:19750581]
Abstract [show]
Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum gamma-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type 2.
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No. Sentence Comment
89 Goto et al[14] have reported four mutations in ABCB11, predicted to yield V330X, R487H, R575X and E636G, in two Japanese PFIC patients.
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ABCB11 p.Glu636Gly 19750581:89:98
status: NEW[hide] The bile salt export pump (BSEP) in health and dis... Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):536-53. doi: 10.1016/j.clinre.2012.06.006. Epub 2012 Jul 12. Kubitz R, Droge C, Stindt J, Weissenberger K, Haussinger D
The bile salt export pump (BSEP) in health and disease.
Clin Res Hepatol Gastroenterol. 2012 Dec;36(6):536-53. doi: 10.1016/j.clinre.2012.06.006. Epub 2012 Jul 12., [PMID:22795478]
Abstract [show]
The bile salt export pump (BSEP) is the major transporter for the secretion of bile acids from hepatocytes into bile in humans. Mutations of BSEP are associated with cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 2 (PFIC-2), benign recurrent intrahepatic cholestasis type 2 (BRIC-2) and genetic polymorphisms are linked to intrahepatic cholestasis of pregnancy (ICP) and drug-induced liver injury (DILI). Detailed analysis of these diseases has considerably increased our knowledge about physiology and pathophysiology of bile secretion in humans. This review focuses on expression, localization, and function, short- and long-term regulation of BSEP as well as diseases association and treatment options for BSEP-associated diseases.
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No. Sentence Comment
185 PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Missense mutations M1V C336S D549V L1055P E135K E137K T87R V43I S701P G19R W342G G556R C1083Y E137K L198P M123T S56L L712L L50S A382G G562D A1110E E186G E297G S194P Q121K A865D M62K R387H A570T S1114R L198P R415Q L198P R128H A865G C68Y A390P L581F G1116E E297G V444A G260D I206V S874P C107R G410D A588V G1116F G374S D482G E297K V284A I939M I112T L413W S593R G1116R A390P N591S V444A G295C R958Q W114R I420T I627T S1120N R432T T655I T510T G295R F959C Y157C D440E E636G R1128C V444A T655I G295S F959V A167T G455E R698C S1144R I498T D676Y R299K T965S A167V K461E S699P R1153C A570T P710P R303K F971L I182K T463I E709K R1153H T586I L827I L339V F971Y M183T Q466K G758R S1154P G648V G855R H423R L1006F M183V R470Q G766R N1173D T655I E1186K V444A N1009H G188W Y472C Y818F T1210P T923P V444D K1145N M217R V481E R832C N1211D A926P V444G I1183T R223C D482G R832H V1212F R948C A459V S226L R487H T859R R1231Q G1004D I468I G238V R487P A865V R1231W R1050C R487L T242I N490D Q869P L1242I G1116R Q546K A257G I498T G877R D1243G R1128H Q558H V284L G499E S901R R1268Q L1197G E592Q E297G I512T R948C A1283V R1231Q V597M R303G N515T N979D G1292V R616G R303K R517H G982R G1298R T619A Q312H F540L G1004D M677L R313S I541L T1029K M677V G327E I541T G1032R R696Q W330R F548Y A1044P R698H Nonsense mutations (premature stop-codons) S25X Y472X Y772X R1090X E96X W493X Q791X V1147X W330X R520X R928X Q1215X Y354X I528X Y1041X R1235X R415X R575X R1057X E1302X R470X Q702X Q1058X Table 1 (Continued) PFIC BRIC/NFC ICP Other liver diseases Genetic variants without disease association Splice site mutations 76 + 3G > T 908 + 1delG 2178 + 1G > T 3057-2A > G Q159Q 77-1G > C 908 + 1G > T 2179-2A > G 3213 + 1delG Q361Q 99-1G > T 908 + 1G > A 2343 + 1G > T 3213 + 4A > G 150 + 3A > C 1435-13 -8del 2343 + 2T > C 3213 + 5G > A 390-1G > A 2012-8T > G 2611-2A > T 611 + 1G > A 2178 + 1G > A R1001R Deletions/insertions/frame shifts Q101Dfs8X L380Wfs18X G648Vfs5X Q1058Hfs38X F959Hfs1X T127Hfs6X A382 A388del K700Sfs12X I1061Vfs34X F959Gfs48X N199Ifs14X P456Pfs24X T919del L1165del L232Cfs9X H484Rfs5X K930Efs92X A1192Efs50X R303Sfs17X I528Sfs21X K930Efs79X T1256Tfs40X V368Rfs27X I610Qfs45X K969 K972del Synonymous variants without disease association R33R F90F L232L I416I G557G I876I A1028A K1145K D36D I134I Y269Y G418G V597V G937G K1070K R52R S136S Q312Q F427F A804A Y981Y T1086T D58D V195V G319G E395E A535A G817G G1004G A1110A The overview shows ࣈ 290 known variants of BSEP on the protein level, except splice site mutations, which are shown on cDNA level.
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ABCB11 p.Glu636Gly 22795478:185:546
status: NEW