HDAC5 Gene

Name	histone deacetylase 5
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 the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HDAC5, a class IIa histone deacetylase, functions as a dynamic regulator of gene expression in diverse tissues by modulating histone acetylation and partnering with transcriptional regulators. In the brain, chronic stress or cocaine exposure promotes the nuclear export and decreased activity of HDAC5 in the nucleus accumbens, thereby increasing histone acetylation at specific loci and sensitizing gene expression programs that underlie the transition from adaptive responses to psychiatric disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In bone, HDAC5 acts as a negative regulator of osteoblast differentiation by enhancing the degradation of Runx2; repression of HDAC5 by microRNA (miR-2861) stabilizes Runx2, thereby facilitating BMP2‐induced osteogenesis and influencing bone formation and mass."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the heart, proper phosphorylation‐dependent regulation of HDAC5 is critical for transcriptional control of key metabolic genes – as demonstrated by the deleterious consequences of expressing a signal‐resistant HDAC5 variant that disrupts the activation of mitochondrial biogenesis coactivators such as PGC-1α – highlighting its role in maintaining cardiac mitochondrial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In skeletal muscle, activation of AMPK leads to site-specific phosphorylation of HDAC5, which results in its nuclear export, derepression of MEF2-dependent transcription, and consequent upregulation of GLUT4 expression to restore energy balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neural stem cells, HDAC5 is recruited by the nuclear receptor TLX to the promoters of genes such as p21 and pten; this interaction is essential for repressing these inhibitors and thereby promoting neural stem cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In vascular endothelium, HDAC5 acts as a transcriptional repressor of angiogenic factors—the silencing of HDAC5 enhances the expression of pro-angiogenic genes like FGF2 and Slit2, thus promoting capillary sprouting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, in osteocytes, HDAC5 negatively regulates the expression of sclerostin (SOST) by binding to and inhibiting the activity of MEF2C at a distal enhancer, thereby modulating the anabolic activity of osteoblasts and influencing bone turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "William Renthal, Ian Maze, Vaishnav Krishnan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2007.09.032"}], "href": "https://doi.org/10.1016/j.neuron.2007.09.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17988634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17988634"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hui Li, Hui Xie, Wei Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI39832"}], "href": "https://doi.org/10.1172/JCI39832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19920351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19920351"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michael P Czubryt, John McAnally, Glenn I Fishman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha ) and mitochondrial function by MEF2 and HDAC5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0337639100"}], "href": "https://doi.org/10.1073/pnas.0337639100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12578979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12578979"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sean L McGee, Bryce J W van Denderen, Kirsten F Howlett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db07-0843"}], "href": "https://doi.org/10.2337/db07-0843"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18184930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18184930"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Guoqiang Sun, Ruth T Yu, Ronald M Evans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0704089104"}], "href": "https://doi.org/10.1073/pnas.0704089104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17873065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17873065"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Carmen Urbich, Lothar Rössig, David Kaluza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-01-196485"}], "href": "https://doi.org/10.1182/blood-2009-01-196485"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19351956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19351956"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marc N Wein, Jordan Spatz, Shigeki Nishimori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC5 controls MEF2C-driven sclerostin expression in osteocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbmr.2381"}], "href": "https://doi.org/10.1002/jbmr.2381"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25271055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25271055"}]}]}]}
Synonyms	NY-CO-9, HD5
Proteins	HDAC5_HUMAN
NCBI Gene ID	10014
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HDAC5 has 10,198 functional associations with biological entities spanning 9 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, sequence feature) extracted from 145 datasets.

Click the + buttons to view associations for HDAC5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HDAC5 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 HDAC5 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 HDAC5 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 HDAC5 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 HDAC5 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 HDAC5 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 HDAC5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving HDAC5 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HDAC5 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 HDAC5 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 HDAC5 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 HDAC5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HDAC5 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 HDAC5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HDAC5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HDAC5 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 HDAC5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HDAC5 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 HDAC5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of HDAC5 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HDAC5 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 HDAC5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HDAC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HDAC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HDAC5 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing HDAC5 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 HDAC5 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 HDAC5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing HDAC5 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HDAC5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HDAC5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HDAC5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HDAC5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HDAC5 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 HDAC5 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 HDAC5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for HDAC5 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HDAC5 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HDAC5 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 HDAC5 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 HDAC5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.