Inhibin subunit beta E (INHBE) (INHBE)

Inhibin subunit beta E (INHBE) is a member of the transforming growth factor-beta (TGF-beta) superfamily that is predominantly expressed in the liver (UniProt P58166). It encodes the beta E subunit, which forms Activin E, a hepatokine involved in the regulation of energy homeostasis and body fat distribution (Sugiyama et al., 2009). Human genetic studies, including large-scale exome sequencing, have identified that loss-of-function variants in the INHBE gene are strongly associated with a favorable metabolic profile, including lower visceral adiposity, reduced waist-to-hip ratio, and a decreased risk of type 2 diabetes (Backman et al., 2021). Because individuals with these genetic variants appear healthy, INHBE mRNA in hepatocytes has emerged as a validated therapeutic target for obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Current therapeutic development, most notably Alnylam Pharmaceuticals' ALN-HBE, utilizes RNA interference (RNAi) to specifically silence INHBE mRNA in the liver (Alnylam Pharmaceuticals, 2023). By reducing the production and secretion of Activin E, these drugs aim to mimic the metabolic benefits observed in individuals with natural genetic deficiency of the protein.

Other names

Activin beta-EInhibin beta-E chainINHBE

RNA interference (siRNA) mediated silencing of INHBE mRNA in hepatocytes to reduce circulating levels of the INHBE protein.