Hypoxia-inducible factor 3 alpha (HIF-3α)

Hypoxia-inducible factor 3 alpha (HIF-3α) is a transcription factor belonging to the basic helix-loop-helix-PAS (bHLH-PAS) family, serving as a key component of the cellular machinery that senses and responds to low oxygen levels (hypoxia) (Source: NIH, Gene ID: 64344). It is encoded by the HIF3A gene, which undergoes extensive alternative splicing to produce multiple isoforms, such as IPAS (inhibitory PAS domain protein) and NEPAS (neonatal and embryonic PAS), each possessing distinct regulatory roles (Source: NIH, PMID: 25936862). While HIF-1α and HIF-2α primarily act as transcriptional activators of genes involved in angiogenesis and glycolysis, HIF-3α often functions as a negative regulator by competing for the common HIF-1β subunit or by binding directly to HIF-1α to prevent its transcriptional activity (Source: NIH, PMID: 26166140). However, certain HIF-3α variants can also act as activators for specific genes, contributing to processes like cell proliferation, apoptosis, and autophagy (Source: ResearchGate, DOI: 10.1042/BJ20090361). Dysregulation of HIF-3α is associated with various diseases, including renal, pancreatic, and cervical cancers, as well as cardiovascular and metabolic disorders (Source: NIH, PMID: 355210). Despite its potential as a therapeutic target for fine-tuning the hypoxic response, no specific small-molecule inhibitors or activators have been clinically approved to date (Source: NIH, PMID: 26166140).

Other names

HIF3AHypoxia-inducible factor 3-alphaPAS domain-containing protein 7MOP7Inhibitory PAS domain proteinIPASNeonatal and embryonic PASNEPASbHLHe17Member of PAS protein 7

Currently, there are no approved drugs specifically targeting HIF-3α. Potential therapeutic strategies involve modulating its expression or activity to fine-tune the cellular response to hypoxia, either by inhibiting its pro-tumorigenic variants or enhancing its inhibitory variants (like IPAS) to suppress HIF-1/2 signaling (Source: NIH, PMID: 26166140).