HDAC8 Gene

HGNC Family	X-linked mental retardation
Name	histone deacetylase 8
Description	Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human histone deacetylase 8 (HDAC8) is a metal‐dependent member of the class I HDAC family that plays multifaceted roles in regulating both chromatin structure and the function of non‐histone proteins. Structural studies have revealed that HDAC8 folds into a single α/β domain with flexible loops surrounding the active site, where conserved residues such as Asp101 and Tyr306 are critical for substrate binding and catalysis; its activity is modulated by divalent metal ions (with Co(II), Fe(II), and Zn(II) supporting activity in a defined order) and even by potassium ions that stabilize its fold."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, HDAC8 deacetylates not only histone substrates but also key non‐histone proteins. By deacetylating the cohesin subunit SMC3, HDAC8 regulates the release of cohesin complexes from chromatin, a process that is vital for proper sister chromatid cohesion and transcriptional regulation; loss‐of‐function mutations in HDAC8 are associated with developmental disorders such as Cornelia de Lange syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, high HDAC8 expression has been linked to enhanced proliferation and poor prognosis in tumors such as neuroblastoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and its selective inhibition can trigger apoptosis in certain hematologic malignancies. Moreover, HDAC8 participates in oncogenic transcriptional repression complexes, for instance by associating with fusion proteins in inv(16) leukemias to repress AML1‐regulated targets"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and it modulates the transcriptional activities of major regulators such as p53"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and ERRα."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, HDAC8 has been found to associate with components of the smooth muscle actin cytoskeleton, thereby influencing cellular contractility in differentiated smooth muscle cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that HDAC8’s unique structural features underlie a diverse range of functions—from the precise deacetylation of substrates involved in chromatin dynamics and sister chromatid cohesion to the modulation of key transcription factors and cytoskeletal elements in both developmental and oncogenic contexts. This multifaceted role not only emphasizes HDAC8’s importance in normal cellular regulation but also highlights its potential as a therapeutic target in cancer and developmental disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alessandro Vannini, Cinzia Volpari, Gessica Filocamo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0404603101"}], "href": "https://doi.org/10.1073/pnas.0404603101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15477595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15477595"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alessandro Vannini, Cinzia Volpari, Paola Gallinari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.embor.7401047"}], "href": "https://doi.org/10.1038/sj.embor.7401047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17721440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17721440"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stephanie L Gantt, Samuel G Gattis, Carol A Fierke "}, {"type": "b", "children": [{"type": "t", "text": "Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi060212u"}], "href": "https://doi.org/10.1021/bi060212u"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16681389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16681389"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kathryn E Cole, Daniel P Dowling, Matthew A Boone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Chem Soc (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/ja205972n"}], "href": "https://doi.org/10.1021/ja205972n"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21790156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21790156"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew A Deardorff, Masashige Bando, Ryuichiro Nakato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11316"}], "href": "https://doi.org/10.1038/nature11316"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22885700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22885700"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ina Oehme, Hedwig E Deubzer, Dennis Wegener, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone deacetylase 8 in neuroblastoma tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-08-0684"}], "href": "https://doi.org/10.1158/1078-0432.CCR-08-0684"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19118036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19118036"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kristie L Durst, Bart Lutterbach, Tanawan Kummalue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.2.607-619.2003"}], "href": "https://doi.org/10.1128/MCB.23.2.607-619.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509458"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "W Yan, S Liu, E Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone deacetylase inhibitors suppress mutant p53 transcription via histone deacetylase 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.81"}], "href": "https://doi.org/10.1038/onc.2012.81"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22391568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22391568"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Frank J Kaiser, Morad Ansari, Diana Braunholz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu002"}], "href": "https://doi.org/10.1093/hmg/ddu002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24403048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24403048"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "David Waltregny, Wendy Glénisson, Siv Ly Tran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.04-2303fje"}], "href": "https://doi.org/10.1096/fj.04-2303fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15772115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15772115"}]}]}]}
Synonyms	CDLS5, MRXS6, CDA07, HD8, HDACL1
Proteins	HDAC8_HUMAN
NCBI Gene ID	55869
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HDAC8 has 7,010 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 124 datasets.

Click the + buttons to view associations for HDAC8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with HDAC8 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HDAC8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HDAC8 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 HDAC8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HDAC8 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 HDAC8 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 HDAC8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HDAC8 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HDAC8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HDAC8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HDAC8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HDAC8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HDAC8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of HDAC8 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 HDAC8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HDAC8 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HDAC8 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HDAC8 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 HDAC8 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 HDAC8 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 HDAC8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HDAC8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HDAC8 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HDAC8 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 HDAC8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.