A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators
Intrahepatic cholestasis is characterized by the accumulation of compounds in the serum that are normally secreted by hepatocytes into the bile. Genes associated with familial intrahepatic cholestasis (FIC) include <i>ATP8B1</i> (FIC1), <i>ABCB11</i> (FIC2), <i>ABCB4<...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2079-7737/10/2/119 |
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| author | Qinghong Li Yue Sun Sven C. D. van IJzendoorn |
| author_facet | Qinghong Li Yue Sun Sven C. D. van IJzendoorn |
| author_sort | Qinghong Li |
| collection | DOAJ |
| description | Intrahepatic cholestasis is characterized by the accumulation of compounds in the serum that are normally secreted by hepatocytes into the bile. Genes associated with familial intrahepatic cholestasis (FIC) include <i>ATP8B1</i> (FIC1), <i>ABCB11</i> (FIC2), <i>ABCB4</i> (FIC3), <i>TJP2</i> (FIC4), <i>NR1H4</i> (FIC5) and <i>MYO5B</i> (FIC6). With advanced genome sequencing methodologies, additional mutated genes are rapidly identified in patients presenting with idiopathic FIC. Notably, several of these genes, <i>VPS33B</i>, <i>VIPAS39</i>, <i>SCYL1</i>, and <i>AP1S1</i>, together with <i>MYO5B</i>, are functionally associated with recycling endosomes and/or the Golgi apparatus. These are components of a complex process that controls the sorting and trafficking of proteins, including those involved in bile secretion. These gene variants therefore suggest that defects in intracellular trafficking take a prominent place in FIC. Here we review these FIC-associated trafficking genes and their variants, their contribution to biliary transporter and canalicular protein trafficking, and, when perturbed, to cholestatic liver disease. Published variants for each of these genes have been summarized in table format, providing a convenient reference for those who work in the intrahepatic cholestasis field. |
| first_indexed | 2024-03-09T05:38:40Z |
| format | Article |
| id | doaj.art-0c56749482394d1cacc9af5a3e6688d6 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T05:38:40Z |
| publishDate | 2021-02-01 |
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| series | Biology |
| spelling | doaj.art-0c56749482394d1cacc9af5a3e6688d62023-12-03T12:26:54ZengMDPI AGBiology2079-77372021-02-0110211910.3390/biology10020119A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking RegulatorsQinghong Li0Yue Sun1Sven C. D. van IJzendoorn2Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsIntrahepatic cholestasis is characterized by the accumulation of compounds in the serum that are normally secreted by hepatocytes into the bile. Genes associated with familial intrahepatic cholestasis (FIC) include <i>ATP8B1</i> (FIC1), <i>ABCB11</i> (FIC2), <i>ABCB4</i> (FIC3), <i>TJP2</i> (FIC4), <i>NR1H4</i> (FIC5) and <i>MYO5B</i> (FIC6). With advanced genome sequencing methodologies, additional mutated genes are rapidly identified in patients presenting with idiopathic FIC. Notably, several of these genes, <i>VPS33B</i>, <i>VIPAS39</i>, <i>SCYL1</i>, and <i>AP1S1</i>, together with <i>MYO5B</i>, are functionally associated with recycling endosomes and/or the Golgi apparatus. These are components of a complex process that controls the sorting and trafficking of proteins, including those involved in bile secretion. These gene variants therefore suggest that defects in intracellular trafficking take a prominent place in FIC. Here we review these FIC-associated trafficking genes and their variants, their contribution to biliary transporter and canalicular protein trafficking, and, when perturbed, to cholestatic liver disease. Published variants for each of these genes have been summarized in table format, providing a convenient reference for those who work in the intrahepatic cholestasis field.https://www.mdpi.com/2079-7737/10/2/119intrahepatic cholestasisVPS33BVIPARMYO5BAP1S1SCYL1 |
| spellingShingle | Qinghong Li Yue Sun Sven C. D. van IJzendoorn A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators Biology intrahepatic cholestasis VPS33B VIPAR MYO5B AP1S1 SCYL1 |
| title | A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators |
| title_full | A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators |
| title_fullStr | A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators |
| title_full_unstemmed | A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators |
| title_short | A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators |
| title_sort | link between intrahepatic cholestasis and genetic variations in intracellular trafficking regulators |
| topic | intrahepatic cholestasis VPS33B VIPAR MYO5B AP1S1 SCYL1 |
| url | https://www.mdpi.com/2079-7737/10/2/119 |
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