**7. Treatment Options for BSEP-Related Diseases**

Impairment in the expression or function of BSEP leads to one of three human disease phenotypes of differing severity: PFIC2, BRIC2 and intrahepatic cholestasis of pregnancy (ICP). Several drugs with the potential to enhance the expression and function of the transporter have been reported. Disease-causing mutations and potential correctors are listed in Table 1 and depicted in the ABCB11 cryo-EM structure in Figure 3.

**Figure 3.** The positions of disease-causing mutations contained in Table 1 are shown in the ABCB11 cryo-EM structure. C-alpha atoms are shown as spheres and colored according to the resulting disease phenotype (PFIC2: red; BRIC2: blue; either PFIC2 or BRIC2: magenta; nonsense mutations: yellow). Outlines and filled colors indicate the domain organization of the transporter in accordance with Figure 1.

OCA's 100

6α

**Table 1.** Synopsis of a subset of disease-causing mutations, for which potential therapeutic interventions have been proposed. The defects, model systems and associated disease phenotypes are indicated. With the exception of the C129Y and G806D variants, the listed mutants represent a subset of a total of 192 disease-associated missense or nonsense mutations that have been identified to date [99]. PFIC2: progressive familial intrahepatic cholestasis type 2, BRIC2: benign recurrent intrahepatic cholestasis type 2,4-PB: 4-phenylbutyrate, CA: cholic acid, CDCA: chenodeoxycholic acid, DCA: deoxycholic acid, UDCA: ursodeoxycholic acid, FXR: farnesoid X receptor.



**Table 1.***Cont.*


**Table1.***Cont.*


Note: 1 Most frequently reported in Japan. 2 E297G and D482G mutations account for 58% of PFIC2 cases in the Western population [119].
