ACSS2 Gene

HGNC Family	Acyl-CoA synthetase family (ACS)
Name	acyl-CoA synthetase short-chain family member 2
Description	This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ACSS2 is a conserved nucleocytosolic enzyme that converts acetate into acetyl‐CoA and thereby plays a multifaceted role in cellular metabolism and gene regulation. In cancer cells facing hypoxic or lipid‐depleted conditions, ACSS2 is upregulated to capture extracellular acetate and channel it into de novo lipogenesis, contributing significantly to fatty acid and phospholipid synthesis and ultimately promoting tumor growth and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, when the canonical acetyl‐CoA generating enzyme ATP‐citrate lyase (ACLY) is compromised, cells compensate by upregulating ACSS2 to maintain sufficient acetyl‐CoA levels for both lipid synthesis and histone acetylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neuronal cells, nuclear ACSS2 localizes to gene regulatory regions where it facilitates “on‐site” production of acetyl‐CoA that is used for histone acetylation and the transcriptional activation of genes related to differentiation and spatial memory."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, in tumor cells ACSS2 can function bi‐directionally—as it may also catalyze the reverse reaction to interconvert acetyl‐CoA and acetate—thus buffering metabolic fluctuations under stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In models of diet‐induced obesity, ACSS2 additionally contributes to hepatic steatosis and systemic fat storage by promoting dietary lipid absorption and regulating the expression of fatty acid oxidation genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, in the context of obesity‐related malignancies, ACSS2 overexpression stabilizes oncogenic factors and further facilitates cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight ACSS2 as a central integrator of acetate metabolism that links nutrient availability with both epigenetic modifications and lipid biosynthesis. This dual role makes ACSS2 a promising target for therapeutic intervention across a range of pathologies including cancer, metabolic liver disease, and neurological disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zachary T Schug, Barrie Peck, Dylan T Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2014.12.002"}], "href": "https://doi.org/10.1016/j.ccell.2014.12.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25584894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25584894"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomoyuki Mashimo, Kumar Pichumani, Vamsidhara Vemireddy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetate is a bioenergetic substrate for human glioblastoma and brain metastases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.11.025"}], "href": "https://doi.org/10.1016/j.cell.2014.11.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25525878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25525878"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mijin Yun, Seong-Hye Bang, Jae Woo Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nucl Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2967/jnumed.109.062703"}], "href": "https://doi.org/10.2967/jnumed.109.062703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19617323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19617323"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Steven Zhao, AnnMarie Torres, Ryan A Henry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.09.069"}], "href": "https://doi.org/10.1016/j.celrep.2016.09.069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27760311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27760311"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Philipp Mews, Greg Donahue, Adam M Drake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature22405"}], "href": "https://doi.org/10.1038/nature22405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28562591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28562591"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yukie Yoshii, Takako Furukawa, Hiroshi Yoshii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1349-7006.2009.01099.x"}], "href": "https://doi.org/10.1111/j.1349-7006.2009.01099.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19445015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19445015"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhiguang Huang, Menglu Zhang, Abigail A Plec, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1806635115"}], "href": "https://doi.org/10.1073/pnas.1806635115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30228117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30228117"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zongwei Li, Huan Liu, Jin He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetyl-CoA Synthetase 2: A Critical Linkage in Obesity-Induced Tumorigenesis in Myeloma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2020.12.011"}], "href": "https://doi.org/10.1016/j.cmet.2020.12.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33406405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33406405"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Guochun Jiang, Don Nguyen, Nancie M Archin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIV latency is reversed by ACSS2-driven histone crotonylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI98071"}], "href": "https://doi.org/10.1172/JCI98071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29457784"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29457784"}]}]}]}
Synonyms	ACECS, ACAS2, DJ1161H23.1, ACSA
Proteins	ACSA_HUMAN
NCBI Gene ID	55902
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ACSS2 has 8,241 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 119 datasets.

Click the + buttons to view associations for ACSS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ACSS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ACSS2 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 ACSS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ACSS2 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 ACSS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ACSS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ACSS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ACSS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ACSS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ACSS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 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 ACSS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ACSS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ACSS2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ACSS2 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 ACSS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ACSS2 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 ACSS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ACSS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ACSS2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ACSS2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ACSS2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.