HIF-1α (HIF1A)

aka HIF-1, HIF-1 alpha, HIF1, MOP1, hypoxia inducible factor 1 subunit alpha

HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.

HIF1A (chromosome 14q23.2) encodes the oxygen-regulated subunit of hypoxia-inducible factor 1, the master transcriptional regulator of the adaptive response to hypoxia: under low oxygen it activates more than 40 genes including erythropoietin, glucose transporters, glycolytic enzymes and VEGF, heterodimerises with ARNT (HIF-1β) to bind DNA, and is essential for embryonic vascularisation, tumour angiogenesis and ischaemic disease (UniProt Q16665). The VHL/HIF pathway record explains that prolyl hydroxylases mark HIF-α for VHL-dependent destruction in normoxia and that VHL loss in most clear-cell renal cancers lets HIF-α accumulate. In OnCo, HIF-1α is named as the isoform belzutifan does not target (belzutifan stops HIF-2α dimerising with HIF-1β) and as the protein whose translation temsirolimus reduces by inhibiting mTORC1.

HIF-1α (HIF1A): what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.

1 · What it is
HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.
2 · What goes wrong in cancer
HIF-1α and HIF-2α share the ARNT partner and many hypoxia genes; the pathway record calls HIF-2α the oncogenic paralogue in renal cell carcinoma, which is why the approved inhibitor was built for that isoform and HIF-1α remains without a direct drug in the corpus.
3 · How drugs use it
No product in this corpus aims at HIF-1α (HIF1A) yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

External identifiers

HIF1AHGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI GeneOMIM

Biology

HIF-1α and HIF-2α share the ARNT partner and many hypoxia genes; the pathway record calls HIF-2α the oncogenic paralogue in renal cell carcinoma, which is why the approved inhibitor was built for that isoform and HIF-1α remains without a direct drug in the corpus.

Where it is found