Hypoxia-inducible factor prolyl hydroxylase 1 (PHD1) (PHD1)

Hypoxia-inducible factor prolyl hydroxylase 1 (PHD1), encoded by the EGLN2 gene, is a key oxygen-sensing enzyme that regulates the stability of hypoxia-inducible factors (HIFs) (UniProt: P59722). Under normal oxygen levels, PHD1 uses molecular oxygen and 2-oxoglutarate to hydroxylate specific proline residues on HIF-alpha subunits, marking them for recognition by the von Hippel-Lindau (VHL) protein and subsequent proteasomal degradation (PubMed: 11292061). In states of hypoxia or pharmacological inhibition, HIF-alpha stabilizes and translocates to the nucleus to activate the transcription of genes involved in erythropoiesis, such as erythropoietin (EPO), and iron metabolism (PubMed: 21386037). Beyond its role in oxygen sensing, PHD1 has been identified as a coactivator for estrogen receptor alpha, suggesting a role in the progression of hormone-sensitive breast cancers (PubMed: 19776355). Therapeutic targeting of PHD1, typically through pan-PHD inhibitors like Roxadustat and Daprodustat, is primarily used to treat anemia associated with chronic kidney disease by stimulating endogenous EPO production (PubMed: 31340090). However, clinical use requires careful monitoring due to risks of hypertension, thromboembolic events, and the potential for promoting tumor angiogenesis (FDA: Jesduvroq Label).

Other names

Egl nine homolog 2EGLN2Prolyl hydroxylase domain-containing protein 1HPH-3HIF-PH1

HIF prolyl hydroxylase inhibitor