HSF2 Gene

Name	heat shock transcription factor 2
Description	The protein encoded by this gene belongs to the HSF family of transcription factors that bind specifically to the heat-shock promoter element and activate transcription. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Heat shock transcription factor 2 (HSF2) has emerged as a multifunctional regulator that integrates stress response, development, and cellular homeostasis. In glioma vascular endothelial cells, for example, HSF2 functions downstream of a long non‐coding RNA/miR‐144 axis to promote the transcription of tight junction proteins (ZO‐1, occludin, and claudin‐5), thereby contributing to the maintenance of blood–tumor barrier integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the reproductive system, genetic studies have implicated HSF2 in spermatogenesis; mutations in HSF2 can exert dominant‐negative effects that potentially underlie cases of idiopathic azoospermia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, during late spermatogenesis HSF2, together with HSF1 and SP1, binds to the promoter of Hspa1b to “bookmark” this gene so that rapid activation can occur during early embryonic development, ensuring embryonic viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n HSF2 also plays important roles in proteostasis and stress adaptation. It induces the expression of protective chaperones such as the small heat shock protein αB‐crystallin by interacting with components of the Set1/MLL histone methyltransferase complex, thereby suppressing aggregation of misfolded proteins (for example, polyglutamine‐expanded proteins) and supporting cellular survival under proteotoxic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Its activity is subject to posttranslational regulation; in both Xenopus and human cells, SUMOylation at lysine 82 enhances HSF2’s DNA‐binding capacity, thus representing an evolutionarily conserved mechanism that modulates its transcriptional output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, HSF2 interacts with the A subunit of protein phosphatase 2A (PP2A), thereby influencing PP2A activity and linking the regulation of heat shock protein expression with cell cycle and other PP2A‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " Its expression is dynamically modulated during cellular differentiation; in hematopoietic cells, HSF2 is specifically upregulated during erythroid commitment, suggesting a role in lineage specification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging high‐throughput screening methodologies have enabled the identification of small molecules and aptamers that modulate HSF2 activity in vivo, highlighting its potential as a therapeutic target in conditions ranging from cancer to neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Moreover, studies in vertebrate cells have shown that HSF2 is activated within the physiological (febrile) range of heat stress, thereby setting the threshold for the overall heat shock response and protecting against the accumulation of misfolded proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " While early hypotheses suggested essential developmental roles for HSF2, knockout studies have indicated that, although it contributes to optimal stress responses and cellular regulation, HSF2 is dispensable for normal development and fertility in mice."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings position HSF2 as a central integrator of stress adaptation, proteostasis, and cell fate determination, with broad implications for tumor biology, reproductive health, and the pathogenesis of protein‐misfolding diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Heng Cai, Yixue Xue, Ping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4331"}], "href": "https://doi.org/10.18632/oncotarget.4331"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26078353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26078353"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lisha Mou, Yadong Wang, Honggang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A dominant-negative mutation of HSF2 associated with idiopathic azoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-012-1234-7"}], "href": "https://doi.org/10.1007/s00439-012-1234-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23064888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23064888"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Donald C Wilkerson, Lynea A Murphy, Kevin D Sarge "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of HSF1 and HSF2 with the Hspa1b promoter in mouse epididymal spermatozoa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.107.066241"}], "href": "https://doi.org/10.1095/biolreprod.107.066241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18434628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18434628"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Donald C Wilkerson, Kevin D Sarge "}, {"type": "b", "children": [{"type": "t", "text": "RNA polymerase II interacts with the Hspa1b promoter in mouse epididymal spermatozoa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reproduction (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/REP-09-0015"}], "href": "https://doi.org/10.1530/REP-09-0015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19336471"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19336471"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Naoki Hayashida "}, {"type": "b", "children": [{"type": "t", "text": "Set1/MLL complex is indispensable for the transcriptional ability of heat shock transcription factor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.10.061"}], "href": "https://doi.org/10.1016/j.bbrc.2015.10.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26478434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26478434"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Roland S Hilgarth, Lynea A Murphy, Colleen M O'Connor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Xenopus heat shock transcription factor-2: conserved role of sumoylation in regulating deoxyribonucleic acid-binding activity of heat shock transcription factor-2 proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1379/csc-8r.1"}], "href": "https://doi.org/10.1379/csc-8r.1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15497507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15497507"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "M L Goodson, Y Hong, R Rogers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M008066200"}], "href": "https://doi.org/10.1074/jbc.M008066200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11278381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11278381"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hongyan Xing, Yiling Hong, Kevin D Sarge "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the PP2A-interacting region of heat shock transcription factor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1379/csc-249r.1"}], "href": "https://doi.org/10.1379/csc-249r.1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17688198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17688198"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Y Hong, E J Lubert, D W Rodgers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of competition between HSF2 and catalytic subunit for binding to the PR65/A subunit of PP2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.2000.2733"}], "href": "https://doi.org/10.1006/bbrc.2000.2733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10872807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10872807"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Y Hong, K D Sarge "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of protein phosphatase 2A activity by heat shock transcription factor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.274.19.12967"}], "href": "https://doi.org/10.1074/jbc.274.19.12967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10224043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10224043"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "L Pirkkala, T P Alastalo, P Nykanen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differentiation lineage-specific expression of human heat shock transcription factor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fasebj.13.9.1089"}], "href": "https://doi.org/10.1096/fasebj.13.9.1089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10336892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10336892"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Levi M Smith, Dwipayan Bhattacharya, Daniel J Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-throughput screening system for inhibitors of human Heat Shock Factor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12192-015-0605-0"}], "href": "https://doi.org/10.1007/s12192-015-0605-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26003133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26003133"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Toyohide Shinkawa, Ke Tan, Mitsuaki Fujimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-04-0330"}], "href": "https://doi.org/10.1091/mbc.E11-04-0330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21813737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21813737"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "D Randy McMillan, Elisabeth Christians, Michael Forster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.22.8005-8014.2002"}], "href": "https://doi.org/10.1128/MCB.22.22.8005-8014.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12391166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12391166"}]}]}]}
Synonyms	HSF 2, HSTF 2
Proteins	HSF2_HUMAN
NCBI Gene ID	3298
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HSF2 has 5,497 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for HSF2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HSF2 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HSF2 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 HSF2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HSF2 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 HSF2 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 HSF2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HSF2 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 HSF2 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 HSF2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HSF2 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 HSF2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HSF2 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 HSF2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HSF2 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 HSF2 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 HSF2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HSF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HSF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HSF2 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 HSF2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HSF2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HSF2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HSF2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HSF2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HSF2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HSF2 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 HSF2 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 HSF2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HSF2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HSF2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HSF2 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 HSF2 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 HSF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HSF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HSF2 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 HSF2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HSF2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing HSF2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HSF2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HSF2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of HSF2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.