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. 2000 Jul;47(1):1–5. doi: 10.1136/gut.47.1.1

The molecular genetics of familial intrahepatic cholestasis

P JANSEN 1, M MULLER 1
PMCID: PMC1727973  PMID: 10861251

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Figure 1  .

Figure 1  

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Putative structure of FIC1. The FIC1 gene has been demonstrated to be mutated in patients with progressive familial intrahepatic cholestasis (PFIC) type 1 and benign recurrent intrahepatic cholestasis (BRIC).20 It encodes a membrane protein with 10 putative transmembrane domains that exhibits homology with proteins with presumed aminophospholipid translocase activity. The green boxes represent P type ATPase signature domains; the red symbols mark mutations.

Figure 2  .

Figure 2  

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Putative structure of BSEP. The BSEP (bile salt export pump) gene has been demonstrated to be mutated in patients with progressive familial intrahepatic cholestasis (PFIC) type 2.31 32 It encodes a membrane protein with 12 putative transmembrane domains that functions as a major bile salt export pump.32 33 The white boxes represent the Walker A and B motifs and the "ABC" signature; the red symbols mark mutations (modified after Strautnieks and colleagues31).

Figure 3  .

Figure 3  

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Bile salt transport. (A) Bile salts are taken up from the blood into the hepatocyte via carrier proteins in the basolateral membrane. These are NTCP or "sodium taurocholate cotransporting protein" and OATP or "organic anion transporting protein". At the canalicular membrane bile salts are transported into the bile canaliculus by the ATP dependent "bile salt export pump" (BSEP). Hepatocanalicular transport of phospholipids, mainly phosphatidylcholine, is mediated by the P-glycoprotein MDR3. (B) In patients with progressive familial intrahepatic cholestasis type 2, BSEP is not expressed.

Figure 4  .

Figure 4  

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Putative structure of MDR3. The MDR3 gene has been demonstrated to be mutated in patients with progressive familial intrahepatic cholestasis (PFIC) type 3.44 45 47 It encodes a membrane protein with 12 putative transmembrane domains that functions as a phosphatidylcholine translocator. The white boxes represent the Walker A and B motifs and the "ABC" signature; the red symbols mark mutations.

Figure 5  .

Figure 5  

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Putative structure of MRP2. The MRP2 gene has been demonstrated to be mutated in patients with Dubin-Johnson syndrome6 52-54 It encodes a membrane protein with 17 putative transmembrane domains that functions as a major export pump for anionic conjugates. The white boxes represent the Walker A and B motifs and the "ABC" signature; the red symbols mark mutations.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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