FOXF1 Gene: Function, Mutations, and Associated Diseases | NCBI, OMIM, ClinVar

FOXF1 (Forkhead Box F1) is a transcription factor belonging to the forkhead family, characterized by a conserved DNA-binding forkhead domain. It plays a critical role in embryonic development, particularly in the formation of the lungs, gastrointestinal tract, and vasculature. FOXF1 regulates cell proliferation, differentiation, and migration during organogenesis. Heterozygous deletions or loss-of-function mutations in FOXF1 cause alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe neonatal lung disorder. The gene is also implicated in vascular development and maintenance of the alveolar epithelium.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Developmental Biology (Reactome: R-HSA-1266738)

• Transcriptional regulation by FOXF1 (Reactome: R-HSA-9616222)

• Lung and vascular development (KEGG: hsa04350

• TGF-beta signaling pathway - indirect)

FOXF1 is a 379-amino acid transcription factor containing a highly conserved forkhead DNA-binding domain. It binds to the consensus sequence 5'-RYMAAYA-3' in promoter regions of target genes. The protein is predominantly nuclear and regulates genes involved in cell cycle, extracellular matrix remodeling, and angiogenesis. FOXF1 is essential for alveolar septation and pulmonary vascular formation. In the absence of functional FOXF1, lung capillary alignment fails, leading to lethal respiratory failure in newborns.