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Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare hepatic disease caused by genetic mutations of <jats:italic>ABCB4<\/jats:italic>. In this study, we characterized 8 <jats:italic>ABCB4<\/jats:italic> mutations found in PFIC3 patients, using <jats:italic>in vitro<\/jats:italic> molecular assays. First, we examined the transport activity of each mutant by measuring its ATPase activity using paclitaxel or phosphatidylcholine. Then, the pathogenic mechanisms by which these mutations affect MDR3 were examined through immunoblotting, cell surface biotinylation, and immunofluorescence. As a result, three <jats:italic>ABCB4<\/jats:italic> mutants showed significantly reduced transport activity. Among these mutants, one mutation A364V, located in intracellular domains, markedly decreased MDR3 expression on the plasma membrane, while the others did not affect the expression. The expression of MDR3 on the plasma membrane and transport activity of A364V was rescued by a pharmacological chaperone, cyclosporin A. Our study provides the molecular mechanisms of <jats:italic>ABCB4<\/jats:italic> mutations and may contribute to the understanding of PFIC3 pathogenesis and the development of a mutation-specific targeted treatment for PFIC3.<\/jats:p>","DOI":"10.1038\/srep26872","type":"journal-article","created":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T09:40:07Z","timestamp":1464946807000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3"],"prefix":"10.1038","volume":"6","author":[{"given":"Hyo Jin","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Won","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin Hye","family":"Noh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong Jee","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choe","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Young","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Ji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heon Yung","family":"Gee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Ha","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,3]]},"reference":[{"key":"BFsrep26872_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ejps.2005.12.003","volume":"27","author":"Y Shitara","year":"2006","unstructured":"Shitara, Y., Horie, T. & Sugiyama, Y. 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