ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population

Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSE...

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Published inCellular and molecular life sciences : CMLS Vol. 74; no. 13; pp. 2513 - 2524
Main Authors Andress, Edward J., Nicolaou, Michael, McGeoghan, Farrell, Linton, Kenneth J.
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.07.2017
Springer Nature B.V
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Abstract Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the canalicular membrane is also critical for bile formation. ABCB4 flops phosphatidylcholine into the outer leaflet of the membrane to be extracted by bile salts in the canalicular space. These mixed micelles reduce the detergent action of the bile salts and protect the biliary tree from their cytotoxic activity. ABCB4 deficiency also causes cholestasis, and might be expected to cause cholangitis and predispose to liver cancer. Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking. Here, we report the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer. All significantly impair the transporter with a range of phenotypes exhibited, including low abundance, intracellular retention, and reduced floppase activity, suggesting that ABCB4 deficiency is the root cause of the pathology in these cases.
AbstractList Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the canalicular membrane is also critical for bile formation. ABCB4 flops phosphatidylcholine into the outer leaflet of the membrane to be extracted by bile salts in the canalicular space. These mixed micelles reduce the detergent action of the bile salts and protect the biliary tree from their cytotoxic activity. ABCB4 deficiency also causes cholestasis, and might be expected to cause cholangitis and predispose to liver cancer. Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking. Here, we report the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer. All significantly impair the transporter with a range of phenotypes exhibited, including low abundance, intracellular retention, and reduced floppase activity, suggesting that ABCB4 deficiency is the root cause of the pathology in these cases.
Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the canalicular membrane is also critical for bile formation. ABCB4 flops phosphatidylcholine into the outer leaflet of the membrane to be extracted by bile salts in the canalicular space. These mixed micelles reduce the detergent action of the bile salts and protect the biliary tree from their cytotoxic activity. ABCB4 deficiency also causes cholestasis, and might be expected to cause cholangitis and predispose to liver cancer. Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking. Here, we report the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer. All significantly impair the transporter with a range of phenotypes exhibited, including low abundance, intracellular retention, and reduced floppase activity, suggesting that ABCB4 deficiency is the root cause of the pathology in these cases.
Author Nicolaou, Michael
Linton, Kenneth J.
McGeoghan, Farrell
Andress, Edward J.
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Cites_doi 10.1016/j.jhep.2012.01.025
10.1053/j.gastro.2011.07.042
10.1053/gast.2003.50144
10.1111/j.1572-0241.2004.04067.x
10.1002/(SICI)1098-2825(1998)12:2<77::AID-JCLA1>3.0.CO;2-G
10.1038/ng0398-219
10.1038/3034
10.1126/sciadv.1600001
10.1046/j.1440-1746.2002.02672.x
10.1074/jbc.272.2.709
10.1016/j.gcb.2010.04.011
10.1038/nmeth.2019
10.1002/hep.20022
10.1007/s00535-015-1110-z
10.1002/path.3019
10.1007/BF01347905
10.1038/ncomms4850
10.1126/science.1168750
10.1016/j.ajpath.2014.10.013
10.1002/hep.26970
10.1158/1541-7786.MCR-07-0172
10.1073/pnas.1320506111
10.1053/j.gastro.2004.04.009
10.1136/gut.38.4.610
10.1023/A:1018831903371
10.1002/hep.20159
10.1038/nature05155
10.1111/j.1478-3231.2009.02148.x
10.1016/0092-8674(93)90380-9
10.1053/j.gastro.2013.10.013
10.1016/j.jhep.2005.06.025
10.1053/gast.2002.35948
10.1053/j.gastro.2013.06.052
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Issue 13
Keywords Liver cancer
Bile flow
Biliary cirrhosis
Inflammatory liver disease
MDR3
Sclerosing cholangitis
Cholestasis
Language English
License Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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References Bull, van Eijk, Pawlikowska, DeYoung, Juijn, Liao, Klomp, Lomri, Berger, Scharschmidt, Knisely, Houwen, Freimer (CR3) 1998; 18
Fickert, Fuchsbichler, Wagner, Zollner, Kaser, Tilg, Krause, Lammert, Langner, Zatloukal, Marschall, Denk, Trauner (CR31) 2004; 127
Choudhury, Tong, Mathavan, Li, Iwata, Zirah, Rebuffat, van Veen, Beis (CR34) 2014; 111
Poupon, Barbu, Chamouard, Wendum, Rosmorduc, Housset (CR5) 2010; 30
Fickert, Zollner, Fuchsbichler, Stumptner, Weiglein, Lammert, Marschall, Tsybrovskyy, Zatloukal, Denk, Trauner (CR9) 2002; 123
CR16
Ikenaga, Liu, Sverdlov, Yoshida, Nasser, Ke, Kang, Popov (CR11) 2015; 185
Groen, Romero, Kunne, Hoosdally, Dixon, Wooding, Williamson, Seppen, Van den Oever, Mok, Paulusma, Linton, Oude Elferink (CR23) 2011; 141
Yamashiki, Kosaka, Nishimura, Watanabe, Nomoto, Ichida (CR28) 1998; 12
Welzel, Graubard, El-Serag, Shaib, Hsing, Davila, McGlynn (CR22) 2007; 5
Iannelli, Collino, Sinha, Radaelli, Nicoli, D’Antiga, Sonzogni, Faivre, Buendia, Sturm, Thompson, Knisely, Natoli, Ghisletti, Ciccarelli (CR7) 2014; 5
Akisawa, Maeda, Tsuda, Nishimori, Morita, Iwasaki, Tomita, Saibara, Onishi, Kiyoku, Enzan (CR21) 1998; 43
Nakayama, Soloway, Nakama, Miyazaki, Ichimiya, Sheen, Ker, Ong, Choi, Boey (CR6) 1986; 31
Razumilava, Gores (CR18) 2013; 11
Schindelin, Arganda-Carreras, Frise, Kaynig, Longair, Pietzsch, Preibisch, Rueden, Saalfeld, Schmid, Tinevez, White, Hartenstein, Eliceiri, Tomancak, Cardona (CR25) 2012; 9
Mauad, van Nieuwkerk, Dingemans, Smit, Schinkel, Notenboom, van den Bergh, Verkruisen, Groen, Oude Elferink (CR10) 1994; 145
Aller, Yu, Ward, Weng, Chittaboina, Zhuo, Harrell, Trinh, Zhang, Urbatsch, Chang (CR33) 2009; 323
Lammert, Wang, Hillebrandt, Geier, Fickert, Trauner, Matern, Paigen, Carey (CR8) 2004; 39
Degiorgio, Crosignani, Colombo, Bordo, Zuin, Vassallo, Syren, Coviello, Battezzati (CR13) 2016; 51
Broome, Olsson, Loof, Bodemar, Hultcrantz, Danielsson, Prytz, Sandberg-Gertzen, Wallerstedt, Lindberg (CR19) 1996; 38
Burak, Angulo, Pasha, Egan, Petz, Lindor (CR20) 2004; 99
Nicolaou, Andress, Zolnerciks, Dixon, Williamson, Linton (CR1) 2012; 226
Rizvi, Gores (CR17) 2013; 145
Nicklisch, Rees, McGrath, Gokirmak, Bonito, Vermeer, Cregger, Loewen, Sandin, Chang, Hamdoun (CR36) 2016; 2
Tougeron, Fotsing, Barbu, Beauchant (CR12) 2012; 57
Smit, Schinkel, Oude Elferink, Groen, Wagenaar, van Deemter, Mol, Ottenhoff, van der Lugt, van Roon (CR2) 1993; 75
Andress, Nicolaou, Romero, Naik, Dixon, Williamson, Linton (CR24) 2014; 59
Popov, Patsenker, Fickert, Trauner, Schuppan (CR30) 2005; 43
Strautnieks, Bull, Knisely, Kocoshis, Dahl, Arnell, Sokal, Dahan, Childs, Ling, Tanner, Kagalwalla, Nemeth, Pawlowska, Baker, Mieli-Vergani, Freimer, Gardiner, Thompson (CR4) 1998; 20
Pauli-Magnus, Kerb, Fattinger, Lang, Anwald, Kullak-Ublick, Beuers, Meier (CR14) 2004; 39
Katzenellenbogen, Mizrahi, Pappo, Klopstock, Olam, Jacob-Hirsch, Amariglio, Rechavi, Domany, Galun, Goldenberg (CR32) 2007; 5
Dawson, Locher (CR35) 2006; 443
Loo, Clarke (CR26) 1997; 272
Lucena, Herrero, Quiroga, Sangro, Garcia-Foncillas, Zabalegui, Sola, Herraiz, Medina, Prieto (CR15) 2003; 124
Poupon, Arrive, Rosmorduc (CR27) 2010; 34
Neuman, Angulo, Malkiewicz, Jorgensen, Shear, Dickson, Haber, Katz, Lindor (CR29) 2002; 17
U Broome (2472_CR19) 1996; 38
TW Loo (2472_CR26) 1997; 272
SC Nicklisch (2472_CR36) 2016; 2
M Yamashiki (2472_CR28) 1998; 12
D Tougeron (2472_CR12) 2012; 57
P Fickert (2472_CR31) 2004; 127
P Fickert (2472_CR9) 2002; 123
F Nakayama (2472_CR6) 1986; 31
2472_CR16
R Poupon (2472_CR27) 2010; 34
TM Welzel (2472_CR22) 2007; 5
M Neuman (2472_CR29) 2002; 17
R Poupon (2472_CR5) 2010; 30
HG Choudhury (2472_CR34) 2014; 111
SS Strautnieks (2472_CR4) 1998; 20
RJP Dawson (2472_CR35) 2006; 443
D Degiorgio (2472_CR13) 2016; 51
K Burak (2472_CR20) 2004; 99
JF Lucena (2472_CR15) 2003; 124
F Iannelli (2472_CR7) 2014; 5
M Katzenellenbogen (2472_CR32) 2007; 5
A Groen (2472_CR23) 2011; 141
S Rizvi (2472_CR17) 2013; 145
EJ Andress (2472_CR24) 2014; 59
N Akisawa (2472_CR21) 1998; 43
JJ Smit (2472_CR2) 1993; 75
C Pauli-Magnus (2472_CR14) 2004; 39
M Nicolaou (2472_CR1) 2012; 226
N Razumilava (2472_CR18) 2013; 11
TH Mauad (2472_CR10) 1994; 145
Y Popov (2472_CR30) 2005; 43
LN Bull (2472_CR3) 1998; 18
J Schindelin (2472_CR25) 2012; 9
N Ikenaga (2472_CR11) 2015; 185
SG Aller (2472_CR33) 2009; 323
F Lammert (2472_CR8) 2004; 39
References_xml – volume: 57
  start-page: 467
  issue: 2
  year: 2012
  end-page: 468
  ident: CR12
  article-title: ABCB4/MDR3 gene mutations and cholangiocarcinomas
  publication-title: J Hepatol
  doi: 10.1016/j.jhep.2012.01.025
  contributor:
    fullname: Beauchant
– volume: 141
  start-page: 1927
  issue: 5
  year: 2011
  end-page: 1937
  ident: CR23
  article-title: Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2011.07.042
  contributor:
    fullname: Oude Elferink
– volume: 124
  start-page: 1037
  issue: 4
  year: 2003
  end-page: 1042
  ident: CR15
  article-title: A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis
  publication-title: Gastroenterology
  doi: 10.1053/gast.2003.50144
  contributor:
    fullname: Prieto
– volume: 99
  start-page: 523
  issue: 3
  year: 2004
  end-page: 526
  ident: CR20
  article-title: Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis
  publication-title: Am J Gastroenterol
  doi: 10.1111/j.1572-0241.2004.04067.x
  contributor:
    fullname: Lindor
– volume: 12
  start-page: 77
  issue: 2
  year: 1998
  end-page: 82
  ident: CR28
  article-title: Analysis of serum cytokine levels in primary biliary cirrhosis patients and healthy adults
  publication-title: J Clin Lab Anal
  doi: 10.1002/(SICI)1098-2825(1998)12:2<77::AID-JCLA1>3.0.CO;2-G
  contributor:
    fullname: Ichida
– volume: 18
  start-page: 219
  issue: 3
  year: 1998
  end-page: 224
  ident: CR3
  article-title: A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis
  publication-title: Nat Genet
  doi: 10.1038/ng0398-219
  contributor:
    fullname: Freimer
– volume: 20
  start-page: 233
  issue: 3
  year: 1998
  end-page: 238
  ident: CR4
  article-title: A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis
  publication-title: Nat Genet
  doi: 10.1038/3034
  contributor:
    fullname: Thompson
– volume: 2
  start-page: e1600001
  issue: 4
  year: 2016
  ident: CR36
  article-title: Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure
  publication-title: Sci Adv
  doi: 10.1126/sciadv.1600001
  contributor:
    fullname: Hamdoun
– volume: 145
  start-page: 1237
  issue: 5
  year: 1994
  end-page: 1245
  ident: CR10
  article-title: Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis
  publication-title: Am J Pathol
  contributor:
    fullname: Oude Elferink
– ident: CR16
– volume: 17
  start-page: 196
  issue: 2
  year: 2002
  end-page: 202
  ident: CR29
  article-title: Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis
  publication-title: J Gastroenterol Hepatol
  doi: 10.1046/j.1440-1746.2002.02672.x
  contributor:
    fullname: Lindor
– volume: 5
  start-page: 1221
  issue: 10
  year: 2007
  end-page: 1228
  ident: CR22
  article-title: Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study
  publication-title: Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc
  contributor:
    fullname: McGlynn
– volume: 272
  start-page: 709
  issue: 2
  year: 1997
  end-page: 712
  ident: CR26
  article-title: Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators
  publication-title: J Biol Chem
  doi: 10.1074/jbc.272.2.709
  contributor:
    fullname: Clarke
– volume: 34
  start-page: 380
  issue: 6–7
  year: 2010
  end-page: 387
  ident: CR27
  article-title: The cholangiographic features of severe forms of ABCB4/MDR3 deficiency-associated cholangiopathy in adults
  publication-title: Gastroenterol Clin Biol
  doi: 10.1016/j.gcb.2010.04.011
  contributor:
    fullname: Rosmorduc
– volume: 9
  start-page: 676
  issue: 7
  year: 2012
  end-page: 682
  ident: CR25
  article-title: Fiji: an open-source platform for biological-image analysis
  publication-title: Nat Methods
  doi: 10.1038/nmeth.2019
  contributor:
    fullname: Cardona
– volume: 39
  start-page: 117
  issue: 1
  year: 2004
  end-page: 128
  ident: CR8
  article-title: Spontaneous cholecysto- and hepatolithiasis in Mdr2/ mice: a model for low phospholipid-associated cholelithiasis
  publication-title: Hepatology (Baltimore Md
  doi: 10.1002/hep.20022
  contributor:
    fullname: Carey
– volume: 51
  start-page: 271
  issue: 3
  year: 2016
  end-page: 280
  ident: CR13
  article-title: ABCB4 mutations in adult patients with cholestatic liver disease: impact and phenotypic expression
  publication-title: J Gastroenterol
  doi: 10.1007/s00535-015-1110-z
  contributor:
    fullname: Battezzati
– volume: 226
  start-page: 300
  issue: 2
  year: 2012
  end-page: 315
  ident: CR1
  article-title: Canalicular ABC transporters and liver disease
  publication-title: J Pathol
  doi: 10.1002/path.3019
  contributor:
    fullname: Linton
– volume: 31
  start-page: 21
  issue: 1
  year: 1986
  end-page: 26
  ident: CR6
  article-title: Hepatolithiasis in East Asia. Retrospective study
  publication-title: Dig Dis Sci
  doi: 10.1007/BF01347905
  contributor:
    fullname: Boey
– volume: 5
  start-page: 3850
  year: 2014
  ident: CR7
  article-title: Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency
  publication-title: Nat Commun
  doi: 10.1038/ncomms4850
  contributor:
    fullname: Ciccarelli
– volume: 323
  start-page: 1718
  issue: 5922
  year: 2009
  end-page: 1722
  ident: CR33
  article-title: Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding
  publication-title: Science
  doi: 10.1126/science.1168750
  contributor:
    fullname: Chang
– volume: 185
  start-page: 325
  issue: 2
  year: 2015
  end-page: 334
  ident: CR11
  article-title: A new Mdr2(/) mouse model of sclerosing cholangitis with rapid fibrosis progression, early-onset portal hypertension, and liver cancer
  publication-title: Am J Pathol
  doi: 10.1016/j.ajpath.2014.10.013
  contributor:
    fullname: Popov
– volume: 59
  start-page: 1921
  issue: 5
  year: 2014
  end-page: 1931
  ident: CR24
  article-title: Molecular mechanistic explanation for the spectrum of cholestatic disease caused by the S320F variant of ABCB4
  publication-title: Hepatology
  doi: 10.1002/hep.26970
  contributor:
    fullname: Linton
– volume: 5
  start-page: 1159
  issue: 11
  year: 2007
  end-page: 1170
  ident: CR32
  article-title: Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice
  publication-title: Mol Cancer Res
  doi: 10.1158/1541-7786.MCR-07-0172
  contributor:
    fullname: Goldenberg
– volume: 111
  start-page: 9145
  issue: 25
  year: 2014
  end-page: 9150
  ident: CR34
  article-title: Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.1320506111
  contributor:
    fullname: Beis
– volume: 127
  start-page: 261
  issue: 1
  year: 2004
  end-page: 274
  ident: CR31
  article-title: Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2004.04.009
  contributor:
    fullname: Trauner
– volume: 11
  start-page: 13
  issue: 1
  year: 2013
  end-page: 21
  ident: CR18
  article-title: Classification, diagnosis, and management of cholangiocarcinoma
  publication-title: Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc
  contributor:
    fullname: Gores
– volume: 38
  start-page: 610
  issue: 4
  year: 1996
  end-page: 615
  ident: CR19
  article-title: Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis
  publication-title: Gut
  doi: 10.1136/gut.38.4.610
  contributor:
    fullname: Lindberg
– volume: 43
  start-page: 2138
  issue: 9
  year: 1998
  end-page: 2142
  ident: CR21
  article-title: Primary biliary cirrhosis associated with cholangiocarcinoma
  publication-title: Dig Dis Sci
  doi: 10.1023/A:1018831903371
  contributor:
    fullname: Enzan
– volume: 39
  start-page: 779
  issue: 3
  year: 2004
  end-page: 791
  ident: CR14
  article-title: BSEP and MDR3 haplotype structure in healthy Caucasians, primary biliary cirrhosis and primary sclerosing cholangitis
  publication-title: Hepatology
  doi: 10.1002/hep.20159
  contributor:
    fullname: Meier
– volume: 443
  start-page: 180
  issue: 7108
  year: 2006
  end-page: 185
  ident: CR35
  article-title: Structure of a bacterial multidrug ABC transporter
  publication-title: Nature
  doi: 10.1038/nature05155
  contributor:
    fullname: Locher
– volume: 30
  start-page: 327
  issue: 2
  year: 2010
  end-page: 331
  ident: CR5
  article-title: Combined features of low phospholipid-associated cholelithiasis and progressive familial intrahepatic cholestasis 3
  publication-title: Liver Int
  doi: 10.1111/j.1478-3231.2009.02148.x
  contributor:
    fullname: Housset
– volume: 75
  start-page: 451
  issue: 3
  year: 1993
  end-page: 462
  ident: CR2
  article-title: Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease
  publication-title: Cell
  doi: 10.1016/0092-8674(93)90380-9
  contributor:
    fullname: van Roon
– volume: 145
  start-page: 1215
  issue: 6
  year: 2013
  end-page: 1229
  ident: CR17
  article-title: Pathogenesis, diagnosis, and management of cholangiocarcinoma
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2013.10.013
  contributor:
    fullname: Gores
– volume: 43
  start-page: 1045
  issue: 6
  year: 2005
  end-page: 1054
  ident: CR30
  article-title: Mdr2 (Abcb4)-/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes
  publication-title: J Hepatol
  doi: 10.1016/j.jhep.2005.06.025
  contributor:
    fullname: Schuppan
– volume: 123
  start-page: 1238
  issue: 4
  year: 2002
  end-page: 1251
  ident: CR9
  article-title: Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles
  publication-title: Gastroenterology
  doi: 10.1053/gast.2002.35948
  contributor:
    fullname: Trauner
– volume: 2
  start-page: e1600001
  issue: 4
  year: 2016
  ident: 2472_CR36
  publication-title: Sci Adv
  doi: 10.1126/sciadv.1600001
  contributor:
    fullname: SC Nicklisch
– volume: 99
  start-page: 523
  issue: 3
  year: 2004
  ident: 2472_CR20
  publication-title: Am J Gastroenterol
  doi: 10.1111/j.1572-0241.2004.04067.x
  contributor:
    fullname: K Burak
– volume: 39
  start-page: 779
  issue: 3
  year: 2004
  ident: 2472_CR14
  publication-title: Hepatology
  doi: 10.1002/hep.20159
  contributor:
    fullname: C Pauli-Magnus
– volume: 9
  start-page: 676
  issue: 7
  year: 2012
  ident: 2472_CR25
  publication-title: Nat Methods
  doi: 10.1038/nmeth.2019
  contributor:
    fullname: J Schindelin
– volume: 59
  start-page: 1921
  issue: 5
  year: 2014
  ident: 2472_CR24
  publication-title: Hepatology
  doi: 10.1002/hep.26970
  contributor:
    fullname: EJ Andress
– volume: 31
  start-page: 21
  issue: 1
  year: 1986
  ident: 2472_CR6
  publication-title: Dig Dis Sci
  doi: 10.1007/BF01347905
  contributor:
    fullname: F Nakayama
– volume: 111
  start-page: 9145
  issue: 25
  year: 2014
  ident: 2472_CR34
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.1320506111
  contributor:
    fullname: HG Choudhury
– volume: 39
  start-page: 117
  issue: 1
  year: 2004
  ident: 2472_CR8
  publication-title: Hepatology (Baltimore Md
  doi: 10.1002/hep.20022
  contributor:
    fullname: F Lammert
– volume: 75
  start-page: 451
  issue: 3
  year: 1993
  ident: 2472_CR2
  publication-title: Cell
  doi: 10.1016/0092-8674(93)90380-9
  contributor:
    fullname: JJ Smit
– volume: 43
  start-page: 2138
  issue: 9
  year: 1998
  ident: 2472_CR21
  publication-title: Dig Dis Sci
  doi: 10.1023/A:1018831903371
  contributor:
    fullname: N Akisawa
– volume: 185
  start-page: 325
  issue: 2
  year: 2015
  ident: 2472_CR11
  publication-title: Am J Pathol
  doi: 10.1016/j.ajpath.2014.10.013
  contributor:
    fullname: N Ikenaga
– volume: 145
  start-page: 1237
  issue: 5
  year: 1994
  ident: 2472_CR10
  publication-title: Am J Pathol
  contributor:
    fullname: TH Mauad
– volume: 43
  start-page: 1045
  issue: 6
  year: 2005
  ident: 2472_CR30
  publication-title: J Hepatol
  doi: 10.1016/j.jhep.2005.06.025
  contributor:
    fullname: Y Popov
– volume: 226
  start-page: 300
  issue: 2
  year: 2012
  ident: 2472_CR1
  publication-title: J Pathol
  doi: 10.1002/path.3019
  contributor:
    fullname: M Nicolaou
– volume: 5
  start-page: 1221
  issue: 10
  year: 2007
  ident: 2472_CR22
  publication-title: Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc
  contributor:
    fullname: TM Welzel
– volume: 20
  start-page: 233
  issue: 3
  year: 1998
  ident: 2472_CR4
  publication-title: Nat Genet
  doi: 10.1038/3034
  contributor:
    fullname: SS Strautnieks
– volume: 124
  start-page: 1037
  issue: 4
  year: 2003
  ident: 2472_CR15
  publication-title: Gastroenterology
  doi: 10.1053/gast.2003.50144
  contributor:
    fullname: JF Lucena
– ident: 2472_CR16
  doi: 10.1053/j.gastro.2013.06.052
– volume: 38
  start-page: 610
  issue: 4
  year: 1996
  ident: 2472_CR19
  publication-title: Gut
  doi: 10.1136/gut.38.4.610
  contributor:
    fullname: U Broome
– volume: 18
  start-page: 219
  issue: 3
  year: 1998
  ident: 2472_CR3
  publication-title: Nat Genet
  doi: 10.1038/ng0398-219
  contributor:
    fullname: LN Bull
– volume: 11
  start-page: 13
  issue: 1
  year: 2013
  ident: 2472_CR18
  publication-title: Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc
  contributor:
    fullname: N Razumilava
– volume: 30
  start-page: 327
  issue: 2
  year: 2010
  ident: 2472_CR5
  publication-title: Liver Int
  doi: 10.1111/j.1478-3231.2009.02148.x
  contributor:
    fullname: R Poupon
– volume: 272
  start-page: 709
  issue: 2
  year: 1997
  ident: 2472_CR26
  publication-title: J Biol Chem
  doi: 10.1074/jbc.272.2.709
  contributor:
    fullname: TW Loo
– volume: 5
  start-page: 1159
  issue: 11
  year: 2007
  ident: 2472_CR32
  publication-title: Mol Cancer Res
  doi: 10.1158/1541-7786.MCR-07-0172
  contributor:
    fullname: M Katzenellenbogen
– volume: 323
  start-page: 1718
  issue: 5922
  year: 2009
  ident: 2472_CR33
  publication-title: Science
  doi: 10.1126/science.1168750
  contributor:
    fullname: SG Aller
– volume: 5
  start-page: 3850
  year: 2014
  ident: 2472_CR7
  publication-title: Nat Commun
  doi: 10.1038/ncomms4850
  contributor:
    fullname: F Iannelli
– volume: 51
  start-page: 271
  issue: 3
  year: 2016
  ident: 2472_CR13
  publication-title: J Gastroenterol
  doi: 10.1007/s00535-015-1110-z
  contributor:
    fullname: D Degiorgio
– volume: 34
  start-page: 380
  issue: 6–7
  year: 2010
  ident: 2472_CR27
  publication-title: Gastroenterol Clin Biol
  doi: 10.1016/j.gcb.2010.04.011
  contributor:
    fullname: R Poupon
– volume: 443
  start-page: 180
  issue: 7108
  year: 2006
  ident: 2472_CR35
  publication-title: Nature
  doi: 10.1038/nature05155
  contributor:
    fullname: RJP Dawson
– volume: 57
  start-page: 467
  issue: 2
  year: 2012
  ident: 2472_CR12
  publication-title: J Hepatol
  doi: 10.1016/j.jhep.2012.01.025
  contributor:
    fullname: D Tougeron
– volume: 12
  start-page: 77
  issue: 2
  year: 1998
  ident: 2472_CR28
  publication-title: J Clin Lab Anal
  doi: 10.1002/(SICI)1098-2825(1998)12:2<77::AID-JCLA1>3.0.CO;2-G
  contributor:
    fullname: M Yamashiki
– volume: 145
  start-page: 1215
  issue: 6
  year: 2013
  ident: 2472_CR17
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2013.10.013
  contributor:
    fullname: S Rizvi
– volume: 127
  start-page: 261
  issue: 1
  year: 2004
  ident: 2472_CR31
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2004.04.009
  contributor:
    fullname: P Fickert
– volume: 141
  start-page: 1927
  issue: 5
  year: 2011
  ident: 2472_CR23
  publication-title: Gastroenterology
  doi: 10.1053/j.gastro.2011.07.042
  contributor:
    fullname: A Groen
– volume: 123
  start-page: 1238
  issue: 4
  year: 2002
  ident: 2472_CR9
  publication-title: Gastroenterology
  doi: 10.1053/gast.2002.35948
  contributor:
    fullname: P Fickert
– volume: 17
  start-page: 196
  issue: 2
  year: 2002
  ident: 2472_CR29
  publication-title: J Gastroenterol Hepatol
  doi: 10.1046/j.1440-1746.2002.02672.x
  contributor:
    fullname: M Neuman
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Snippet Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the...
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SubjectTerms ABC transporter
Abundance
Adenosine Triphosphatases - metabolism
Amino Acid Substitution - genetics
ATP Binding Cassette Transporter, Subfamily B - genetics
Bile
Bile salts
Binding
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cancer
Cell Biology
Cell Membrane - metabolism
Cholangitis
Cholestasis
Cyclosporine - pharmacology
Cytotoxicity
Detergents
Diseases
Etiology
Exports
Gallbladder diseases
Genetic Predisposition to Disease
Glycosylation
HEK293 Cells
Hepatocytes
Human populations
Humans
Intracellular
Intracellular Space - metabolism
Lecithin
Life Sciences
Lipids - chemistry
Liver
Liver cancer
Liver diseases
Micelles
Missense mutation
Molecular Chaperones - metabolism
Mutant Proteins - metabolism
Mutation
Mutation, Missense - genetics
Original
Original Article
Pathology
Patients
Phosphatidylcholine
Phosphatidylcholines - metabolism
Polymorphism, Single Nucleotide - genetics
Population
Protein Stability - drug effects
Protein Transport - drug effects
Salts
Signal transduction
Signaling
Single-nucleotide polymorphism
Subcellular Fractions - metabolism
Vitamins
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Title ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population
URI https://link.springer.com/article/10.1007/s00018-017-2472-6
https://www.ncbi.nlm.nih.gov/pubmed/28220208
https://www.proquest.com/docview/1910235149
https://pubmed.ncbi.nlm.nih.gov/PMC5487885
Volume 74
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