GLI family zinc finger 3 (GLI3)

GLI family zinc finger 3 (GLI3) is a transcription factor in the GLI-Kruppel family characterized by five C2H2-type zinc finger domains that recognize specific DNA motifs to regulate gene transcription[2][3]. GLI3 is a key downstream effector in the Hedgehog (Hh) signaling pathway, switching between transcriptional activator (full-length, GLI3-FL) and repressor (truncated, GLI3-R) forms in response to Hh ligand availability[2]. Mutations in GLI3 cause developmental syndromes such as Greig cephalopolysyndactyly and Pallister-Hall syndrome, reflecting its role in organ patterning, limb formation, and central nervous system development[2]. GLI3 is implicated in several cancers, where it regulates proliferation, angiogenesis, and migration, though it can have tumor-promoting or tumor-suppressing roles depending on the context[2]. Although no drugs directly target GLI3, inhibitors of the Hedgehog pathway (e.g., vismodegib) impact its activity upstream[2]. GLI3 is also essential for the regulation of immune cell development and may have biomarker potential in disease-stratified patient populations[2][1].

Other names

Gli3GLI3-FL (full-length)GLI3-R (repressor)GLI-Kruppel family member 3

Hedgehog pathway inhibition (prevents activation/processing of GLI3); Promotes degradation or suppresses transcriptional activity of GLI3