Hypoxia-inducible factor 2-alpha (HIF2α), also known as EPAS1. is a key transcriptional regulator of cellular responses to low oxygen levels. As a subunit of the heterodimeric HIF complex, it binds to hypoxia-response elements (HREs) in target genes, activating pathways for angiogenesis, erythropoiesis, and metabolic adaptation. Unlike its paralog HIF1α, HIF2α exhibits tissue-specific expression, prominently in endothelial cells, lung, and placenta, and demonstrates distinct regulatory roles in iron metabolism and catecholamine synthesis.
HIF2α stabilization under hypoxia enables tumor progression by promoting cancer cell survival, metastasis, and therapy resistance. Its dysregulation is linked to clear cell renal cell carcinoma (ccRCC), pheochromocytomas, and congenital erythrocytosis. Germline mutations in HIF2α are associated with Pacak-Zhuang syndrome, while somatic mutations drive sporadic cancers.
HIF2α antibodies are essential tools for detecting protein expression and activation status in research and diagnostics. They are widely used in techniques like Western blotting, immunohistochemistry (IHC), and immunofluorescence to study hypoxia-related pathologies and therapeutic responses. Specific monoclonal antibodies (e.g., clone D9E5) help differentiate HIF2α from HIF1α, crucial given their overlapping functions but divergent clinical implications. Recent pharmaceutical development of HIF2α inhibitors (e.g., belzutifan) for VHL syndrome-associated tumors has further elevated the importance of reliable HIF2α detection in both basic research and clinical biomarker validation. Antibody validation remains critical due to cross-reactivity risks and context-dependent protein expression patterns.