HSPB8 Gene

HGNC Family	Heat shock proteins
Name	heat shock 22kDa protein 8
Description	The protein encoded by this gene belongs to the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain at the C-terminal part of the molecule. The expression of this gene in induced by estrogen in estrogen receptor-positive breast cancer cells, and this protein also functions as a chaperone in association with Bag3, a stimulator of macroautophagy. Thus, this gene appears to be involved in regulation of cell proliferation, apoptosis, and carcinogenesis, and mutations in this gene have been associated with different neuromuscular diseases, including Charcot-Marie-Tooth disease. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HSPB8 is a small heat shock protein that acts as an ATP‐independent molecular chaperone and is emerging as a critical regulator of protein homeostasis in several tissues, particularly in neurons and muscle. Mutations in HSPB8, which affect key residues within its α‐crystallin domain (e.g. K141N/K141E), impair its chaperone function, enhance aberrant self‐ and hetero–oligomerization with other small heat shock proteins, and lead to intracellular aggregate formation that is associated with distal motor neuropathies and Charcot–Marie–Tooth disease (<!-- (1) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", <!-- (12) -->."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In normal and stressed cells, HSPB8 forms a stable complex with the co‐chaperone BAG3 and Hsp70 that facilitates the recognition and autophagic clearance of aggregation‐prone proteins – including mutant superoxide dismutase 1, polyglutamine‐expanded huntingtin, TDP-43 fragments, and even α-synuclein – thereby mitigating proteotoxic stress that underlies neurodegenerative disorders such as amyotrophic lateral sclerosis and Parkinson’s disease (<!-- (2) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", <!-- (3) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", <!-- (6) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", <!-- (7) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", <!-- (14) -->."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, HSPB8 can be secreted or function extracellularly to activate innate immune receptors such as TLR4, thereby contributing to the inflammatory milieu observed in disorders including rheumatoid arthritis (<!-- (4) -->."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Its participation in the chaperone-assisted selective autophagy (CASA) pathway further enables cells to sense and remove mechanically damaged proteins, thus maintaining structural integrity under stress conditions (<!-- (5) -->."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, HSPB8 expression is upregulated in response to cellular stress and is subject to regulation by pathways such as NF-κB, which, by enhancing the BAG3–HSPB8 complex, promotes aggrephagy and cell survival under conditions of proteotoxic and heat stress (<!-- (13) -->"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", <!-- (11) -->."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifunctional role of HSPB8 in safeguarding cells from the deleterious effects of misfolded protein accumulation, and they highlight its potential as a therapeutic target in a variety of neuromuscular and neurodegenerative diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joy Irobi, Katrien Van Impe, Pavel Seeman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1328"}], "href": "https://doi.org/10.1038/ng1328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15122253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15122253"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jean-Marc Fontaine, Xiankui Sun, Adam D Hoppe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.06-5911fje"}], "href": "https://doi.org/10.1096/fj.06-5911fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16935933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16935933"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Serena Carra, Samuel J Seguin, Herman Lambert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HspB8 chaperone activity toward poly(Q)-containing proteins depends on its association with Bag3, a stimulator of macroautophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M706304200"}], "href": "https://doi.org/10.1074/jbc.M706304200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18006506"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18006506"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Valeria Crippa, Daniela Sau, Paola Rusmini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq257"}], "href": "https://doi.org/10.1093/hmg/ddq257"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20570967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20570967"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Serena Carra, Samuel J Seguin, Jacques Landry "}, {"type": "b", "children": [{"type": "t", "text": "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/auto.5407"}], "href": "https://doi.org/10.4161/auto.5407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18094623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18094623"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Serena Carra, Mitchel Sivilotti, Aura T Chávez Zobel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HspB8, a small heat shock protein mutated in human neuromuscular disorders, has in vivo chaperone activity in cultured cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi174"}], "href": "https://doi.org/10.1093/hmg/ddi174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15879436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15879436"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Valeria Crippa, Maria Elena Cicardi, Nandini Ramesh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The chaperone HSPB8 reduces the accumulation of truncated TDP-43 species in cells and protects against TDP-43-mediated toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw232"}], "href": "https://doi.org/10.1093/hmg/ddw232"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27466192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27466192"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mieke F Roelofs, Wilbert C Boelens, Leo A B Joosten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.176.11.7021"}], "href": "https://doi.org/10.4049/jimmunol.176.11.7021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16709864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16709864"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anna Ulbricht, Felix J Eppler, Victor E Tapia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2013.01.064"}], "href": "https://doi.org/10.1016/j.cub.2013.01.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23434281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23434281"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mathieu Nivon, Michel Abou-Samra, Emma Richet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF-κB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.091041"}], "href": "https://doi.org/10.1242/jcs.091041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22302993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22302993"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lei Ke, Roelien A M Meijering, Femke Hoogstra-Berends, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in tachypaced atrial myocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0020395"}], "href": "https://doi.org/10.1371/journal.pone.0020395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21731611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21731611"}]}]}]}
Synonyms	HMN2A, E2IG1, DHMN2, HMN2, HSP22, CMT2L, H11
Proteins	HSPB8_HUMAN
NCBI Gene ID	26353
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HSPB8 has 11,344 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 127 datasets.

Click the + buttons to view associations for HSPB8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 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 HSPB8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HSPB8 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 HSPB8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with HSPB8 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HSPB8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HSPB8 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 HSPB8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HSPB8 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 HSPB8 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with HSPB8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HSPB8 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HSPB8 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 HSPB8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HSPB8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HSPB8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing HSPB8 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HSPB8 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 HSPB8 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HSPB8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HSPB8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HSPB8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HSPB8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HSPB8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HSPB8 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HSPB8 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HSPB8 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 HSPB8 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 HSPB8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HSPB8 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 HSPB8 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 HSPB8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.