HSD3B7 Gene - Bile Acid Synthesis and Congenital Bile Acid Synthesis Defect Type 1

HSD3B7 encodes the enzyme 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase, which catalyzes the second step in the classic bile acid synthesis pathway, converting 7α-hydroxy-cholest-5-en-3-one to 7α-hydroxy-3-oxo-cholest-4-en-3-one. This enzyme is critical for the production of cholic acid and chenodeoxycholic acid. Mutations in HSD3B7 cause congenital bile acid synthesis defect type 1 (CBAS1), an autosomal recessive disorder characterized by progressive cholestasis, giant cell hepatitis, and liver failure in infancy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Bile acid biosynthesis (Reactome: R-HSA-193368)

• Metabolism of steroids (Reactome: R-HSA-8957322)

HSD3B7 encodes a 369-amino acid protein localized to the endoplasmic reticulum membrane. It belongs to the short-chain dehydrogenase/reductase (SDR) family and functions as a bifunctional enzyme with both 3β-hydroxysteroid dehydrogenase and Δ5→Δ4 isomerase activities, specifically for C27 bile acid intermediates. The enzyme is essential for the conversion of 7α-hydroxy-cholest-5-en-3-one to 7α-hydroxy-3-oxo-cholest-4-en-3-one in the classic bile acid synthesis pathway. Deficiency leads to accumulation of toxic monohydroxy bile acids and impaired production of primary bile acids.