FoxA

FoxA refers to the Forkhead box A family of transcription factors in animals, comprising FOXA1, FOXA2, and FOXA3. These proteins belong to the forkhead/winged-helix family and share a conserved DNA-binding forkhead domain. They are widely regarded as pioneer transcription factors because they can bind compacted chromatin and facilitate the recruitment of other transcription factors to regulatory elements.

FoxA factors regulate endoderm development and the formation and function of several endoderm-derived organs, including the liver, pancreas, lungs, and gastrointestinal tract. In vertebrates, FOXA1/FOXA2 are essential for liver and pancreatic development and for early foregut patterning, while FOXA3 is prominent in visceral endoderm and mucosal tissues. In adults, FOXA proteins continue to regulate tissue-specific gene expression, metabolism, and hormone-responsive pathways.

In humans, the genes FOXA1, FOXA2, and FOXA3 encode the A family members and have overlapping as well as distinct expression patterns. Genetic studies in model organisms show that loss of FoxA genes disrupts organ morphogenesis and lineage specification. Clinically, altered expression of FOXA1/FOXA2 has been observed in various cancers, including breast and prostate cancer, where they influence hormone receptor signaling and tumor cell identity. FoxA factors are also studied for their roles in liver diseases and metabolic regulation.

For context, the FoxA family is named after the founding Drosophila forkhead gene family; the human genes are commonly referred to as FOXA1, FOXA2, and FOXA3, with historical aliases HNF3A, HNF3B, and HNF3G (hepatocyte nuclear factor 3 alpha/beta/gamma).