HIF1A Gene

HGNC Family	Basic helix-loop-helix proteins (BHLH)
Name	hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)
Description	This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hypoxia‐inducible factor 1α (HIF1A) is a master transcriptional regulator that orchestrates the cellular response to reduced oxygen availability by linking oxygen sensing to diverse physiological processes. Under hypoxic conditions, diminished activity of prolyl hydroxylases (which include key isoforms such as those described in"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "leads to stabilization of HIF1A through inefficient hydroxylation, while interactions with regulatory proteins such as VHL and FIH‐1 further modulate its transactivation function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Stabilized HIF1A then translocates to the nucleus where it binds to hypoxia‐responsive elements (HREs) in target gene promoters, thereby upregulating genes essential for adaptive responses."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the vascular compartment, HIF1A directly activates vascular endothelial growth factor (VEGF) transcription to promote neovascularization in settings of ischemia and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " HIF1A also plays a central role in metabolic reprogramming by inducing the expression of glycolytic enzymes and pyruvate dehydrogenase kinase 1 (PDK1), which shifts metabolism from mitochondrial oxidative phosphorylation to glycolysis, thereby minimizing reactive oxygen species production and favoring cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Its transcriptional activity is further enhanced by coactivators such as PKM2, which, upon post‐translational modification, engages with HIF1A to promote downstream gene expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and is modulated by mTOR signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of immune regulation, HIF1A is a critical mediator of inflammation and immune cell fate. In myeloid cells, for example, stabilization of HIF1A by metabolites such as succinate contributes to the upregulation of interleukin‐1β"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while it is required for effective cell infiltration and bactericidal functions of myeloid cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Moreover, HIF1A governs the expression of immune checkpoint molecules like PD-L1 on myeloid-derived suppressor cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "and influences the balance between T helper 17 and regulatory T cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n HIF1A further contributes to tumor progression by driving epithelial-to-mesenchymal transition (EMT) through activation of transcription factors such as TWIST, thereby promoting metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Aberrant HIF1A activation—such as that observed in the context of IDH1 mutations in gliomas—leads to enhanced tumor cell survival and angiogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and in endothelial cells, HIF1A mediates cell-autonomous responses that contribute to basement membrane invasion and tube formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, HIF1A modulates the tumor microenvironment by altering the function and differentiation of myeloid-derived suppressor cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and its activity is differentially balanced with that of HIF-2α in cancers such as renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Epigenetic regulators, for example SIRT6, further fine-tune HIF1A-driven transcriptional programs, impacting glucose homeostasis and cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that HIF1A functions as a central mediator linking oxygen availability to angiogenesis, metabolic reprogramming, immune responses, and tumor progression. Its activity is intricately controlled by oxygen-dependent regulators and coactivators, ensuring that the cellular response is appropriately tailored to hypoxic stress"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": " \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Edurne Berra, Emmanuel Benizri, Amandine Ginouvès, et al. 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Synonyms	HIF-1-alpha, HIF1-ALPHA, HIF-1A, HIF1, PASD8, BHLHE78, HIF-1ALPHA, MOP1
Proteins	HIF1A_HUMAN
NCBI Gene ID	3091
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HIF1A has 27,331 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 135 datasets.

Click the + buttons to view associations for HIF1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HIF1A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HIF1A gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HIF1A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HIF1A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of HIF1A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HIF1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of HIF1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HIF1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving HIF1A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HIF1A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HIF1A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HIF1A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of HIF1A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HIF1A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of HIF1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with HIF1A gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HIF1A gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HIF1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HIF1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of HIF1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HIF1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HIF1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HIF1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HIF1A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HIF1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with HIF1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HIF1A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HIF1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HIF1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HIF1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HIF1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HIF1A gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HIF1A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HIF1A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HIF1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with HIF1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with HIF1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HIF1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HIF1A protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HIF1A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HIF1A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.