Forkhead box protein A3 (FOXA3)

Forkhead box protein A3 (FOXA3) is a DNA-binding transcription factor of the forkhead box family, formerly known as hepatocyte nuclear factor 3-gamma (HNF-3G)[4][5]. It functions as a "pioneer" factor, opening compacted chromatin and serving as a transcriptional activator for liver-specific genes such as albumin, transthyretin, and gluconeogenic genes, and modulates both lipid and glucose homeostasis[4][5]. FOXA3 regulates hepatocyte proliferation and liver regeneration by activating transcription of key genes such as CEBPB and protects against atherosclerosis by upregulating apolipoprotein A-I (ApoA-I) expression and enhancing reverse cholesterol transport[1][2]. In adipose tissue, FOXA3 is a direct target and co-factor of the glucocorticoid receptor, mediating glucocorticoid-induced expansion of visceral fat and age-associated declines in metabolic function[3][6]. Loss or gain of FOXA3 function influences liver repair, fat accumulation, energy expenditure, and overall metabolic health, making it a promising but complex therapeutic target for metabolic diseases, liver injury, and cardiovascular risk[1][2][3][6].

Other names

Hepatocyte nuclear factor 3-gammaHNF-3GTCF-3GFork head-related protein FKH H3Transcription factor 3GFKHH3

Transcriptional modulation: drugs/compounds affecting expression or activity of FOXA3 alter transcription of metabolic and regenerative gene targets (e.g., CEBPB, ApoA-I)[1][2]