HSPA4 Gene

HGNC Family	Heat shock proteins
Name	heat shock 70kDa protein 4
Description	Predicted to enable adenyl-nucleotide exchange factor activity. Involved in chaperone-mediated protein complex assembly and protein insertion into mitochondrial outer membrane. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HSPA4, a member of the HSP70 family, plays a multifaceted role in maintaining cellular homeostasis under stress by acting as a molecular chaperone. In its intracellular role, HSPA4 facilitates the proper folding of nascent polypeptides, prevents protein aggregation, and assists in the quality‐control processes that govern protein turnover. In addition, HSPA4 participates in specialized trafficking events; for instance, chaperones related to the HSP70 family are recruited to organellar import receptors to deliver preproteins for membrane translocation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, HSPA4 works together with co‐chaperones and ubiquitin ligases—such as CHIP—to regulate ubiquitin-dependent degradation of misfolded proteins, a mechanism that is relevant to neuroprotective as well as tumor suppressive pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its intracellular functions, extracellular forms of HSP70 proteins—which include HSPA4 homologues—can be actively secreted via exosomal pathways without relying on the classical endoplasmic reticulum–Golgi route."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Once in the extracellular milieu, these chaperones interact with innate immune receptors, such as Toll-like receptors TLR2 and TLR4, to trigger proinflammatory cytokine production and modulate immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " This dual functionality—promoting both intracellular proteostasis and extracellular signaling—positions HSPA4 as an important mediator in processes that span from stress resilience to the regulation of inflammation, cancer progression, and neurodegenerative disease."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HSPA4 contributes to the maintenance of proteome integrity by assisting in protein folding and targeting damaged proteins for degradation, while its extracellular release and receptor interactions facilitate intercellular communication in stress and disease contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " These combined activities underscore its potential as a therapeutic target in conditions ranging from cancer and chronic inflammation to neurodegeneration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jason C Young, Nicholas J Hoogenraad, F Ulrich Hartl "}, {"type": "b", "children": [{"type": "t", "text": "Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(02)01250-3"}], "href": "https://doi.org/10.1016/s0092-8674(02"}, {"type": "t", "text": "01250-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12526792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12526792"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuzuru Imai, Mariko Soda, Shigetsugu Hatakeyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00583-x"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00583-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12150907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12150907"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Minghao Zhang, Mark Windheim, S Mark Roe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2005.09.023"}], "href": "https://doi.org/10.1016/j.molcel.2005.09.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16307917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16307917"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Graeme I Lancaster, Mark A Febbraio "}, {"type": "b", "children": [{"type": "t", "text": "Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502017200"}], "href": "https://doi.org/10.1074/jbc.M502017200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15826944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15826944"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexzander Asea, Michael Rehli, Edith Kabingu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200497200"}], "href": "https://doi.org/10.1074/jbc.M200497200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11836257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11836257"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ramunas M Vabulas, Parviz Ahmad-Nejad, Sanghamitra Ghose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111204200"}], "href": "https://doi.org/10.1074/jbc.M111204200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11842086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11842086"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jürgen Radons "}, {"type": "b", "children": [{"type": "t", "text": "The human HSP70 family of chaperones: where do we stand?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12192-016-0676-6"}], "href": "https://doi.org/10.1007/s12192-016-0676-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26865365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26865365"}]}]}]}
Synonyms	HS24/P52, HSP70RY, RY, HEL-S-5A, HSP70, APG-2, HSPH2
Proteins	HSP74_HUMAN
NCBI Gene ID	3308
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HSPA4 has 17,494 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 128 datasets.

Click the + buttons to view associations for HSPA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HSPA4 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 HSPA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with HSPA4 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HSPA4 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HSPA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HSPA4 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 HSPA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HSPA4 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HSPA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HSPA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HSPA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HSPA4 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 HSPA4 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 HSPA4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HSPA4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HSPA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HSPA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HSPA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HSPA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HSPA4 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 HSPA4 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 HSPA4 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 HSPA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HSPA4 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 HSPA4 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 HSPA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HSPA4 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 HSPA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HSPA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.