AACS Gene

HGNC Family	Acyl-CoA synthetase family (ACS)
Name	acetoacetyl-CoA synthetase
Description	Predicted to enable acetoacetate-CoA ligase activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Acetoacetyl‐CoA synthetase (AACS) is a cytosolic enzyme that catalyzes the conversion of acetoacetate to acetoacetyl‐CoA, thereby providing a critical precursor for the de novo synthesis of cholesterol and fatty acids. This enzyme plays a central role in lipid metabolism in a variety of tissues. In adipose tissue, AACS is highly expressed and its transcription is regulated by key adipogenic transcription factors such as C/EBPα, PPARγ, and Sp1, which are essential for normal adipocyte differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the liver, AACS is selectively induced by nuclear receptors—for example, it is upregulated by PXR—and contributes to cholesterol homeostasis, as evidenced by reduced blood cholesterol levels upon its knockdown."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neuronal contexts, AACS expression increases during neurite outgrowth in a SREBP‐2–dependent manner, and its activity appears to support neuronal lipogenesis and differentiation; promoter studies in Neuro‐2a cells further highlight Sp1 as a key regulator of AACS expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Notably, AACS has also been identified as part of a BRAF V600E–specific gene signature in papillary thyroid carcinoma, suggesting a potential link between its metabolic function and oncogenic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, post‐translational regulation of AACS has been observed; cleavage by legumain at Asn547 abolishes its enzymatic activity and is associated with altered caveolin‐1 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, genetic association studies have implicated regions downstream of AACS in insulin resistance, further underscoring its potential role in metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shinya Hasegawa, Masahiro Yamasaki, Tasuku Inage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of ketone body-utilizing enzyme, acetoacetyl-CoA synthetase, by C/EBPalpha during adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2008.05.001"}], "href": "https://doi.org/10.1016/j.bbagrm.2008.05.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18514076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18514076"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Francesca Aguiló, Nuria Camarero, Joana Relat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20090851"}], "href": "https://doi.org/10.1042/BJ20090851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20102333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20102333"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shinya Hasegawa, Yotaro Ikeda, Masahiro Yamasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, in 3T3-L1 adipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.b12-00435"}], "href": "https://doi.org/10.1248/bpb.b12-00435"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23123469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23123469"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hiroki Tojima, Satoru Kakizaki, Yuichi Yamazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ligand dependent hepatic gene expression profiles of nuclear receptors CAR and PXR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.toxlet.2012.06.001"}], "href": "https://doi.org/10.1016/j.toxlet.2012.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22698814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22698814"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shinya Hasegawa, Kazuki Noda, Akina Maeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by SREBP-2 and affects serum cholesterol levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2012.08.017"}], "href": "https://doi.org/10.1016/j.ymgme.2012.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22985732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22985732"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shinya Hasegawa, Hiroki Kume, Sayuri Iinuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetoacetyl-CoA synthetase is essential for normal neuronal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.09.076"}], "href": "https://doi.org/10.1016/j.bbrc.2012.09.076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23000407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23000407"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shinya Hasegawa, Masahiko Imai, Masahiro Yamasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of acetoacetyl-CoA synthetase by Sp1 in neuroblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.11.068"}], "href": "https://doi.org/10.1016/j.bbrc.2017.11.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29137983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29137983"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dagmara Rusinek, Michal Swierniak, Ewa Chmielik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0143688"}], "href": "https://doi.org/10.1371/journal.pone.0143688"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26625260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26625260"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shinya Hasegawa, Daiki Inoue, Masahiro Yamasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Site-specific cleavage of acetoacetyl-CoA synthetase by legumain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.12197"}], "href": "https://doi.org/10.1002/1873-3468.12197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27129883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27129883"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sara Haydar, Florin Grigorescu, Mădălina Vintilă, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fine-scale haplotype mapping of MUT, AACS, SLC6A15 and PRKCA genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0214122"}], "href": "https://doi.org/10.1371/journal.pone.0214122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30913280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30913280"}]}]}]}
Synonyms	ACSF1, SUR-5
Proteins	AACS_HUMAN
NCBI Gene ID	65985
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AACS has 5,799 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 113 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

AACS 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 AACS gene relative to other tissues from the Allen Brain Atlas Adult Human 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 AACS 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 AACS 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 AACS 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 AACS 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 AACS 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 AACS 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 AACS 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 AACS 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 AACS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AACS 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 AACS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AACS 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 AACS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AACS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AACS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AACS 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 AACS 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 AACS 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 AACS 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 AACS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AACS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AACS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AACS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by AACS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with AACS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with AACS 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 AACS 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 AACS 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 AACS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at AACS 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 AACS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AACS 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 AACS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with AACS gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of AACS gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AACS 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 AACS from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of AACS gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of AACS gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.