{"entity":{"id":"hif1a","kind":"target","name":"HIF-1α (HIF1A)","aka":["HIF-1","HIF-1 alpha","HIF1","MOP1","hypoxia inducible factor 1 subunit alpha"],"tldr":"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.","summary":"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.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:4910","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4910"},{"label":"UniProt Q16665","url":"https://www.uniprot.org/uniprotkb/Q16665/entry"},{"label":"NCBI Gene 3091","url":"https://www.ncbi.nlm.nih.gov/gene/3091"}],"tags":["wave5-target"],"related":["belzutifan","temsirolimus","hif2a","mtor","vegf"],"cancers":["rcc","clear-cell-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl","angiogenic-switch","cancer-metabolism","renal-cell-carcinoma-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"HIF1A","hgnc":"HGNC:4910","ensembl":"ENSG00000100644","uniprot":"Q16665","entrez":"3091","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.","whereFound":["Hypoxic regions of solid tumours","Clear-cell renal cell carcinoma (VHL loss stabilises HIF-α)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/hif1a/","neighbours":{"drug":[{"id":"belzutifan","kind":"drug","name":"Belzutifan","route":"/drugs/belzutifan/"},{"id":"temsirolimus","kind":"drug","name":"Temsirolimus","route":"/drugs/temsirolimus/"}],"target":[{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"},{"id":"mtor","kind":"target","name":"mTOR","route":"/targets/mtor/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"cancer":[{"id":"clear-cell-rcc","kind":"cancer","name":"Clear cell renal cell carcinoma","route":"/cancers/clear-cell-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"pathway":[{"id":"cancer-metabolism","kind":"pathway","name":"Cancer metabolism","route":"/pathways/cancer-metabolism/"},{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG map)","route":"/pathways/renal-cell-carcinoma-signalling/"},{"id":"angiogenic-switch","kind":"pathway","name":"The angiogenic switch & tumour vessels","route":"/pathways/angiogenic-switch/"},{"id":"hif-vhl","kind":"pathway","name":"VHL / HIF oxygen sensing","route":"/pathways/hif-vhl/"}]}}