Folding Defects in P-Type Atp 8B1 Associated With Hereditary Cholestasis Are Ameliorated by 4-Phenylbutyrate

Abstract

A surprisingly large proportion of ATP8B1 mutations resulted in aberrant folding and decreased expression at the plasma membrane. These effects were partially restored by treatment with 4-phenylbutyrate. We propose that treatment with pharmacological chaperones may represent an effective therapeutic strategy to ameliorate the recurrent attacks of cholestasis in patients with intermittent (BRIC1) disease.