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Target intelligence / Profile preview
Hypoxia-inducible factor 2-alpha
- Molecular classification
- Transcription factor, bHLH-PAS family
01
Overview
Hypoxia-inducible factor 2-alpha (HIF-2α), also known as Endothelial PAS domain-containing protein 1 (EPAS1), is a transcription factor that plays a central role in the cellular response to low oxygen levels (hypoxia). It belongs to the basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) family of transcription factors. HIF-2α is one of three main HIF-α isoforms, with distinct tissue distribution and biological functions compared to HIF-1α and HIF-3α. It regulates genes involved in angiogenesis, erythropoiesis, glycolysis/energy metabolism, cell proliferation/differentiation/death pathways. HIF-2α is a validated drug target, with inhibitors like belzutifan approved for treating VHL-associated tumors.
- Other names
- Endothelial PAS domain-containing protein 1EPAS1HIF-2A
02
Mechanism of action
Inhibition of HIF-2α by binding to the PAS-B domain, disrupting heterodimer formation with ARNT and blocking downstream gene activation.
03
Biological functions
Transcriptional regulationAngiogenesisErythropoiesisGlycolysis/energy metabolismCell proliferationCell differentiationCell death
04
Disease associations
CancerRenal cell carcinomaNeuroblastomavon Hippel-Lindau disease
05
Interacting drugs
Belzutifan
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