ASNS Gene

Name	asparagine synthetase (glutamine-hydrolyzing)
Description	The protein encoded by this gene is involved in the synthesis of asparagine. This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Asparagine synthetase (ASNS) is an ATP‐dependent enzyme that catalyzes the conversion of aspartate and glutamine into asparagine and glutamate, a reaction central to maintaining amino acid homeostasis under metabolic stress. Its expression is robustly induced under conditions of nutrient deprivation and endoplasmic reticulum stress via activation of the PERK–eIF2α–ATF4 pathway, which binds nutrient‐sensing response elements in the ASNS promoter."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In tumor cells, elevated ASNS activity enables continued protein synthesis and cell survival despite amino acid and glucose limitations; indeed, overexpression of ASNS or exogenous asparagine supplementation can rescue proliferation when upstream stress regulators such as ATF4 are inhibited."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in certain malignancies such as acute lymphoblastic leukemia, low intrinsic ASNS levels render tumor cells exquisitely sensitive to asparagine depletion therapies, while high ASNS expression in the tumor microenvironment can confer resistance by providing exogenous asparagine."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In KRAS‐mutant colorectal cancers, ASNS is upregulated through the PI3K–AKT–mTOR signaling cascade to support asparagine biosynthesis necessary for proliferation and migration; targeting ASNS in these settings impairs tumor growth and enhances therapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Conversely, tumor suppressor signals such as those mediated by p53 can downregulate ASNS expression, thereby tipping the balance of asparagine–aspartate homeostasis and promoting growth arrest or senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additionally, transcriptional repressors like CHOP can modulate ASNS induction during stress responses, fine tuning the cell’s adaptive capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings underscore the dual role of ASNS as an essential metabolic enzyme that supports tumor cell survival under adverse conditions and as a potential therapeutic target whose expression can determine sensitivity to amino acid–depleting strategies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jiangbin Ye, Monika Kumanova, Lori S Hart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.81"}], "href": "https://doi.org/10.1038/emboj.2010.81"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20473272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20473272"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fai Siu, Perry J Bain, Rene LeBlanc-Chaffin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201959200"}], "href": "https://doi.org/10.1074/jbc.M201959200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11960987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11960987"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hong Chen, Yuan-Xiang Pan, Elizabeth E Dudenhausen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M409173200"}], "href": "https://doi.org/10.1074/jbc.M409173200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15385533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15385533"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Carrie L Lomelino, Jacob T Andring, Robert McKenna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Asparagine synthetase: Function, structure, and role in disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.R117.819060"}], "href": "https://doi.org/10.1074/jbc.R117.819060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29084849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29084849"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shotaro Iwamoto, Keichiro Mihara, James R Downing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI30235"}], "href": "https://doi.org/10.1172/JCI30235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17380207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17380207"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mukundh N Balasubramanian, Elizabeth A Butterworth, Michael S Kilberg "}, {"type": "b", "children": [{"type": "t", "text": "Asparagine synthetase: regulation by cell stress and involvement in tumor biology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00015.2013"}], "href": "https://doi.org/10.1152/ajpendo.00015.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23403946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23403946"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kosuke Toda, Kenji Kawada, Masayoshi Iwamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metabolic Alterations Caused by KRAS Mutations in Colorectal Cancer Contribute to Cell Adaptation to Glutamine Depletion by Upregulation of Asparagine Synthetase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2016.09.004"}], "href": "https://doi.org/10.1016/j.neo.2016.09.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27764698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27764698"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Longfei Deng, Pengbo Yao, Le Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p53-mediated control of aspartate-asparagine homeostasis dictates LKB1 activity and modulates cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-15573-6"}], "href": "https://doi.org/10.1038/s41467-020-15573-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32273511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32273511"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nan Su, Michael S Kilberg "}, {"type": "b", "children": [{"type": "t", "text": "C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene."}]}, {"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.M806874200"}], "href": "https://doi.org/10.1074/jbc.M806874200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18940792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18940792"}]}]}]}
Synonyms	ASNSD, TS11
Proteins	ASNS_HUMAN
NCBI Gene ID	440
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ASNS has 16,466 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, 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 ASNS from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ASNS 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 ASNS 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 ASNS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of ASNS 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 ASNS 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 ASNS 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 ASNS 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 ASNS 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 ASNS 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 ASNS 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 ASNS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ASNS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ASNS 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 ASNS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ASNS 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 ASNS 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 ASNS gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ASNS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ASNS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ASNS 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 ASNS 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 ASNS 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 ASNS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ASNS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ASNS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ASNS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ASNS 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 ASNS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ASNS gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ASNS 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 ASNS 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 ASNS 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 ASNS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ASNS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ASNS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ASNS 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 ASNS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ASNS 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 ASNS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of ASNS gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ASNS gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.