Affinage

ASNS

Asparagine synthetase [glutamine-hydrolyzing] · UniProt P08243

Length
561 aa
Mass
64.4 kDa
Annotated
2026-06-09
46 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASNS is the metabolic enzyme that catalyzes ATP-dependent de novo asparagine biosynthesis, with catalysis residing in a C-terminal synthetase domain where AMP, Mg2+, and pyrophosphate define the active-site architecture [PMID:bio_10.1101_2025.10.16.682859]; disease-associated missense substitutions (R49Q, G289A, T337I) that diminish AMP-producing catalytic activity establish the enzyme's clinical importance (PMID:37965492). Its expression is governed primarily at the transcriptional level by the amino acid response: GCN2 kinase signaling drives recruitment of ATF4 to the ASNS promoter at the NSRE-1 element, where ATF4 binding is accompanied by activating histone marks (H3K4me3, H4 acetylation), to induce transcription during amino acid or asparagine deprivation (PMID:17276738, PMID:22978410, PMID:30061420, PMID:38844625). ASNS abundance is further set by layered post-transcriptional and post-translational control: mRNA stability is enhanced by METTL3-mediated m6A modification (PMID:39132158), while protein turnover is shaped by ubiquitin-proteasome degradation involving mTORC1 (which protects ASNS from degradation) (PMID:37542132) and the VHL E3 ligase (which ubiquitinates ASNS) (PMID:41943831); the upstream ATF4 driver is itself stabilized by GPS2 blocking its BTRC-mediated degradation (PMID:40693356). Through this regulatory network ASNS modulates cellular asparagine supply with consequences for L-asparaginase sensitivity in leukemia (PMID:32573712), CD8+ T cell effector differentiation (PMID:36384124), and cortical neurogenesis (PMID:37382163), and it is being pharmacologically targeted: the uncompetitive inhibitor ASX-173 binds the synthetase-domain ASNS/AMP/Mg2+/pyrophosphate complex and, combined with asparaginase, induces the integrated stress response and antitumor effects [PMID:bio_10.1101_2025.10.16.682859, PMID:bio_10.1101_2025.07.03.662851].

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 Medium

    Established the transcriptional logic of ASNS induction by identifying ATF4 as the activator acting through the NSRE-1 promoter element under metabolic stress.

    Evidence Reporter assay of NSRE-1, ATF4 RNAi knockdown, and microarray in MELAS/NARP cybrid cells

    PMID:17276738

    Open questions at the time
    • Did not resolve the chromatin events accompanying ATF4 binding
    • Upstream kinase signaling not defined in this study
  2. 2013 Medium

    Defined the chromatin dynamics of ASNS activation, showing ATF4 recruitment coincides with specific histone modifications and reversible promoter remodeling during the amino acid response.

    Evidence ChIP for ATF4 and histone marks plus transcription run-on assays in HepG2 cells

    PMID:22978410

    Open questions at the time
    • Functional necessity of each histone mark for induction not dissected
    • Did not establish the signaling kinase upstream of ATF4
  3. 2018 Medium

    Placed GCN2 kinase upstream of ASNS in the amino acid response, linking sensing of asparagine depletion to ASNS induction and to asparaginase sensitivity in cancer.

    Evidence Pharmacological GCN2 inhibition with expression profiling, in vitro viability, and mouse xenografts in ALL/AML/pancreatic models

    PMID:30061420

    Open questions at the time
    • Relied on pharmacological inhibition rather than genetic ablation
    • Direct GCN2-ATF4-ASNS molecular chain not reconstituted
  4. 2020 Medium

    Connected epigenetic silencing of ASNS to drug response by showing allele-specific promoter methylation suppresses ASNS and predicts asparaginase sensitivity in leukemia.

    Evidence Bisulfite/allele-specific methylation mapping across three BCP-ALL cohorts and an ETV6-RUNX1 knockin mouse model

    PMID:32573712

    Open questions at the time
    • Mechanism linking 7q21 imprinting cluster to ASNS not fully defined
    • Causal contribution of methylation versus correlation not isolated
  5. 2022 Medium

    Tested the prevailing assumption that ASNS level dictates asparaginase resistance, finding feedback suppression of biosynthesis by asparagine and that ASNS overexpression alone is insufficient for resistance in vivo.

    Evidence 13C-glutamine isotope tracing and ASNS overexpression in a mouse B cell lymphoma model

    PMID:35857457

    Open questions at the time
    • Microenvironmental asparagine sources not fully accounted for
    • Mechanism of biosynthetic feedback suppression not molecularly defined
  6. 2022 Medium

    Extended ASNS function beyond housekeeping metabolism by identifying its expression dynamics as a regulator of CD8+ T cell effector versus memory differentiation.

    Evidence Single-cell RNA-seq, ASNS overexpression, and adoptive transfer in a mouse melanoma model

    PMID:36384124

    Open questions at the time
    • Metabolic versus signaling basis of the differentiation effect unresolved
    • Whether catalytic activity is required not tested
  7. 2023 High

    Quantified the catalytic consequences of ASNS deficiency mutations, directly linking specific missense variants to graded loss of enzymatic activity.

    Evidence In vitro AMP-production assays of purified FLAG-tagged R49Q, G289A, T337I variants from HEK293T cells

    PMID:37965492

    Open questions at the time
    • Structural basis of activity loss for each variant not resolved
    • Effects on protein stability or folding not separated from catalysis
  8. 2023 Medium

    Identified dual upstream control of ASNS by TLK2, acting through ATF4 transcription and through mTORC1-mediated protection of ASNS protein from degradation.

    Evidence IP-MS, co-IP, and ubiquitination assays with pathway modulators

    PMID:37542132

    Open questions at the time
    • E3 ligase opposing mTORC1 protection not identified here
    • Direct versus indirect nature of mTORC1-ASNS interaction not fully resolved
  9. 2023 Medium

    Confirmed direct ATF4 binding to the ASNS promoter in an independent cancer context, reinforcing the GCN2-ATF4-ASNS transcriptional axis.

    Evidence ChIP-qPCR with ATF4 gain- and loss-of-function in SW480 colon cancer cells

    PMID:38844625

    Open questions at the time
    • Did not add new mechanistic layers beyond confirming direct binding
  10. 2023 Medium

    Positioned ASNS downstream of DOT1L/EZH2 epigenetic regulation in cortical neurogenesis, where elevated ASNS promotes neuronal differentiation.

    Evidence DOT1L inhibition, scRNA-seq, lineage tracing, and ASNS overexpression rescue in neural progenitors

    PMID:37382163

    Open questions at the time
    • Direct transcriptional link from EZH2/PRC2 to ASNS not defined
    • Whether the effect requires ASNS catalysis untested
  11. 2024 Medium

    Revealed m6A-based post-transcriptional control of ASNS, with METTL3 stabilizing ASNS mRNA to maintain protein levels and growth.

    Evidence MeRIP-qPCR, actinomycin D stability assay, luciferase reporter, and overexpression rescue

    PMID:39132158

    Open questions at the time
    • m6A reader mediating stability not identified
    • Specific m6A sites on ASNS mRNA not mapped
  12. 2025 High

    Defined the structural basis for therapeutic targeting of ASNS by solving an inhibitor-bound cryo-EM structure and showing uncompetitive inhibition that lowers asparagine and triggers the integrated stress response.

    Evidence Cryo-EM of ASX-173/ASNS/AMP/Mg2+/pyrophosphate plus in vitro kinetics and thermal shift assays (preprint)

    PMID:bio_10.1101_2025.10.16.682859

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Selectivity against related synthetases not detailed
  13. 2025 Medium

    Identified additional ubiquitin-proteasome and transcriptional repression nodes (VHL ubiquitination of ASNS; GPS2 stabilization of ATF4; HDAC5/RXRA repression) that set ASNS abundance and downstream signaling.

    Evidence Co-IP, ubiquitination/TMT proteomics, ChIP, and luciferase assays with in vivo validation across RCC, ALL, and cancer models

    PMID:40693356 PMID:40781327 PMID:41943831

    Open questions at the time
    • Hierarchy among these regulators in a single cell type not established
    • Reciprocal validation of some interactions limited to single labs
  14. 2025 Medium

    Advanced ASNS as a druggable target with two distinct small-molecule inhibitors (ASX-173, PGG) showing antitumor and metabolic effects through enzymatic inhibition.

    Evidence Biochemical inhibition of purified ASNS, cellular and metabolic readouts, and mouse AML xenograft / MASLD models

    PMID:40409103 PMID:bio_10.1101_2025.07.03.662851

    Open questions at the time
    • Long-term resistance mechanisms not addressed
    • ASX-173 evidence partly from preprint

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple parallel regulatory layers (GCN2/ATF4 transcription, m6A/m7G mRNA modification, mTORC1/VHL/GPS2-BTRC turnover, and epigenetic silencing) are integrated to set ASNS activity in a given tissue or tumor remains unresolved.
  • No unified model relating transcriptional, post-transcriptional, and degradative control
  • Tissue-specific dominance of each regulatory node unknown
  • Relationship between ASNS catalytic output and its non-metabolic signaling roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0140657 ATP-dependent activity 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ATF4MTORC1TLK2USP13VHL

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 Cryo-EM structure reveals that ASX-173 binds a unique hydrophobic pocket formed by AMP, Mg2+, and pyrophosphate in the C-terminal synthetase domain of human ASNS; in vitro kinetic and thermal shift assays show ASX-173 binds the ASNS/Mg2+/ATP complex as an uncompetitive inhibitor, reducing cellular asparagine levels and inducing the integrated stress response. Cryo-EM structure determination, in vitro kinetic assays, thermal shift assays, cellular asparagine measurement bioRxivpreprint High bio_10.1101_2025.10.16.682859
2023 Purified FLAG-tagged ASNS variants R49Q, G289A, and T337I associated with ASNS deficiency show reductions in enzymatic activity of 90%, 36%, and 96% respectively, as measured by AMP production in vitro, establishing that disease-causing ASNS mutations reduce catalytic activity. In vitro enzymatic assay (AMP detection) of purified FLAG-tagged ASNS variants from stably expressing HEK 293T cells Biology methods & protocols High 37965492
2006 In cybrid cells harboring MELAS and NARP mtDNA mutations, ASNS transcription is upregulated via ATF4 binding to the NSRE-1 (nutrient-sensing response element-1) in the ASNS promoter; ATF4 knockdown by RNAi reduced ASNS transcription, establishing ATF4 as a transcriptional activator of ASNS. Reporter assay (NSRE-1 element), RNA interference (ATF4 knockdown), DNA microarray, western blot Mitochondrion Medium 17276738
2013 During amino acid response (AAR) activation, ATF4 is recruited to the ASNS promoter, accompanied by increases in histone H3K4me3 and H4 acetylation marks and a concurrent loss of total histone H3 near the promoter; removal of AAR stress rapidly reverses H4Ac and ATF4 binding but not H3K4me3, and a second AAR challenge does not alter the kinetics of ASNS induction. Chromatin immunoprecipitation (ChIP), transcription run-on assays, histone modification analysis in HepG2 cells The Biochemical journal Medium 22978410
2018 GCN2 kinase is required for ASNS induction in response to L-asparaginase-induced asparagine depletion; pharmacological GCN2 inhibition prevents ASNS upregulation and sensitizes ASNS-low cancer cells (ALL, AML, pancreatic cancer) to asparaginase in vitro and in vivo, placing GCN2 upstream of ASNS in the amino acid response pathway. GCN2 inhibitor treatment, gene-expression profiling, in vitro cell viability, in vivo mouse xenograft models Proceedings of the National Academy of Sciences of the United States of America Medium 30061420
2023 ATF4 directly binds the ASNS promoter region (ChIP-qPCR) and its overexpression upregulates p-GCN2 and ASNS expression, while ATF4 knockdown reduces ASNS transcription, confirming ATF4 as a direct transcriptional activator of ASNS in colon cancer cells. ChIP-qPCR, RT-qPCR, western blot, ATF4 knockdown and overexpression in SW480 cells Scientific reports Medium 38844625
2023 TLK2 promotes ASNS expression via two mechanisms: (1) TLK2 directly interacts with ATF4 (a transcription factor for ASNS) and promotes its expression at the mRNA level; (2) mTORC1 directly interacts with ASNS protein and inhibits its ubiquitin-proteasome degradation. TLK2 knockdown suppresses amino acid synthesis by downregulating the mTORC1 pathway and ASNS expression. IP-MS, co-immunoprecipitation, ubiquitination assay, pathway inhibitor/activator experiments, western blot Cancer gene therapy Medium 37542132
2024 METTL3-mediated m6A modification of ASNS mRNA promotes its stability; METTL3 inhibition (STM2457) or knockdown reduces m6A modification on ASNS mRNA, decreasing ASNS mRNA stability and protein expression; ASNS overexpression rescues growth defects caused by METTL3 inhibition. MeRIP-qPCR, mRNA stability assay (actinomycin D), western blot, overexpression rescue, dual-luciferase reporter Journal of Cancer Medium 39132158
2025 HDAC5 deacetylates RXRA at K410 and K412, stabilizing RXRA by reducing ubiquitination; deacetylated RXRA acts as a transcriptional repressor of ASNS by binding the -1114/-1104 region of the ASNS promoter, thereby suppressing asparagine synthesis. CCT196969 inhibits HDAC5, leading to increased RXRA acetylation and decreased ASNS transcription. Co-immunoprecipitation, ChIP assay, luciferase reporter assay, mass spectrometry (deacetylation site mapping), CETSA, SPR, IP/ubiquitination assay Journal of experimental & clinical cancer research Medium 40781327
2026 VHL E3 ubiquitin ligase interacts with ASNS protein and promotes its ubiquitination and degradation; ASNS overexpression activates PI3K-AKT and MAPK signaling pathways by binding to and inhibiting Junction plakoglobin (JUP) expression, promoting RCC cell growth and metastasis. Immunoprecipitation, ubiquitination modification proteomics, western blotting, TMT proteomics, RNA sequencing, cell phenotype and animal experiments International journal of biological sciences Medium 41943831
2025 GPS2 binds ATF4 protein and stabilizes it by blocking the interaction between ATF4 and its E3 ubiquitin ligase BTRC, thereby preventing ubiquitin-proteasome degradation of ATF4 and maintaining elevated ASNS expression, which confers L-asparaginase resistance in ALL cells. Co-immunoprecipitation (GPS2-ATF4 and ATF4-BTRC interactions), ubiquitination assay, GPS2 knockdown in vitro and xenograft in vivo Carcinogenesis Medium 40693356
2020 ASNS CpG island promoter is allele-specifically methylated in BCP-ALL cells (aberrant imprinting), which silences ASNS gene expression; higher ASNS methylation correlates with lower ASNS protein expression and higher L-asparaginase sensitivity in three BCP-ALL cohorts. This methylation is associated with aberrant methylation of an imprinted gene cluster at 7q21. Bisulfite sequencing, methylation analysis, allele-specific methylation mapping, protein expression analysis, in vitro asparaginase sensitivity assays, ETV6-RUNX1 knockin mouse model Blood Medium 32573712
2022 In vitro, supraphysiological or physiological concentrations of asparagine suppress de novo asparagine biosynthesis by ASNS regardless of ASNS expression level, as shown by [U-13C5]-L-glutamine isotope tracing; overexpressing ASNS in ASNase-sensitive B cell lymphoma was insufficient to confer resistance to ASNase in vivo. 13C isotope tracing ([U-13C5]-L-glutamine) in vitro and in vivo, ASNS overexpression in mouse B cell lymphoma model Science advances Medium 35857457
2022 ASNS expression peaks in effector CD8+ T cells and declines during memory formation; ASNS overexpression promotes an effector phenotype and enhances anti-tumor responses of adoptively transferred CD8+ T cells in a mouse melanoma model, establishing ASNS expression dynamics as a functional modulator of T cell differentiation. Single-cell RNA sequencing, ASNS overexpression in CD8+ T cells, adoptive transfer in mouse melanoma model, functional differentiation assays Cell reports Medium 36384124
2023 DOT1L inhibition reduces EZH2/PRC2 pathway activity, which converges on increased ASNS expression; overexpression of ASNS in apical progenitors (APs) phenocopies DOT1L inhibition by increasing neuronal differentiation, placing ASNS downstream of DOT1L/EZH2 epigenetic regulation in cortical neurogenesis. DOT1L inhibitor treatment, single-cell RNA sequencing, lineage tracing, ASNS overexpression in neural progenitors, clonal analysis EMBO reports Medium 37382163
2025 METTL1-mediated m7G modification of ASNS mRNA increases its stability and expression in hepatocellular carcinoma; METTL1 knockdown reduces ASNS mRNA stability and expression, while METTL1 drives HCC progression through ASNS-dependent asparagine metabolism and mTOR pathway activation. Multi-omics analysis (m7G modification mapping), mRNA stability assay, METTL1 knockdown and overexpression, mTOR pathway analysis Oncogene Low 42045536
2021 In Saccharomyces cerevisiae, ASNS (Asn1) forms cytoophidia (filamentous assemblies) that are shorter than CTP synthase (CTPS) cytoophidia; disruption of ASNS shortens CTPS cytoophidial length, but CTPS deletion does not affect ASNS cytoophidium formation or ASNS protein level. ASNS overexpression in diauxic phase induces multi-dot structures, suggesting protein level drives cytoophidia formation. Genetic deletion (ASNS and CTPS knockouts in yeast), fluorescence microscopy of cytoophidia, protein level analysis G3 (Bethesda, Md.) Low 33561249
2025 ASNS protein binds USP13 and increases USP13 expression; in ARPE-19 retinal epithelial cells, ASNS overexpression reduces ROS production and SA-β-gal staining (senescence marker), and enhances glycolysis and oxidative phosphorylation, suggesting ASNS acts through an ASNS/USP13 axis to protect against oxidative stress. Co-immunoprecipitation (ASNS-USP13), ASNS overexpression, ROS measurement, SA-β-gal staining, ECAR/OCR measurement in ARPE-19 cells BioFactors (Oxford, England) Low 41293996
2025 PGG (1,2,3,4,6-O-Pentagalloylglucose) inhibits purified recombinant human ASNS with KD = 8.8 μM and IC50 = 7.1 μM in enzymatic assay, thereby increasing cellular L-aspartate levels and activating the LKB1/AMPK metabolic axis, reducing hepatic lipid accumulation in mice on high-fat/high-cholesterol diet. FEP-based virtual screening, binding affinity assay (KD), in vitro enzymatic inhibition assay (IC50), cellular aspartate measurement, LKB1/AMPK pathway analysis, in vivo mouse MASLD model International immunopharmacology Medium 40409103
2025 ASX-173 is a cell-permeable small molecule that inhibits ASNS at nanomolar concentrations; combination of ASX-173 with L-asparaginase disrupts nucleotide synthesis and induces cell cycle arrest and apoptosis; in a mouse AML xenograft model, the combination significantly delayed tumor growth. Biochemical ASNS inhibition assay, cell viability assays, cell cycle/apoptosis analysis, nucleotide synthesis measurement, mouse xenograft model bioRxivpreprint Medium bio_10.1101_2025.07.03.662851

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response. Proceedings of the National Academy of Sciences of the United States of America 149 30061420
2014 The glutaminase activity of L-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood 148 24659632
2016 Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells. Scandinavian journal of gastroenterology 40 27251594
2022 CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation. Cell reports 36 36384124
2016 Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report. BMC neurology 31 27422383
2006 CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. Mitochondrion 29 17276738
1983 Isolation and characterization of interspecific heat-resistant hybrids between a temperature-sensitive chinese hamster cell asparaginyl-tRNA synthetase mutant and normal human leukocytes: assignment of human asnS gene to chromosome 18. Somatic cell genetics 27 6836455
2022 Tumoral microenvironment prevents de novo asparagine biosynthesis in B cell lymphoma, regardless of ASNS expression. Science advances 26 35857457
2019 Clinical outcomes of two patients with a novel pathogenic variant in ASNS: response to asparagine supplementation and review of the literature. Human genome variation 24 31123592
1994 Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15. Cytogenetics and cell genetics 24 7904551
2021 Therapeutic Assessment of Targeting ASNS Combined with l-Asparaginase Treatment in Solid Tumors and Investigation of Resistance Mechanisms. ACS pharmacology & translational science 22 33615182
2020 Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL. Blood 22 32573712
2016 Diaphragmatic Eventration in Sisters with Asparagine Synthetase Deficiency: A Novel Homozygous ASNS Mutation and Expanded Phenotype. JIMD reports 22 27469131
2018 Novel Mutations in the Asparagine Synthetase Gene (ASNS) Associated With Microcephaly. Frontiers in genetics 19 30057589
2013 Asparagine synthetase (ASNS) gene polymorphism is associated with the outcome of childhood acute lymphoblastic leukemia by affecting early response to treatment. Leukemia research 19 24268318
2023 DOT1L activity affects neural stem cell division mode and reduces differentiation and ASNS expression. EMBO reports 16 37382163
2019 Molecular diagnosis of asparagine synthetase (ASNS) deficiency in two Indian families and literature review of 29 ASNS deficient cases. Gene 15 30978478
2013 Cell cycle-dependent recruitment of polycomb proteins to the ASNS promoter counteracts C/ebp-mediated transcriptional activation in Bombyx mori. PloS one 13 23382816
2023 Targeting TLK2 inhibits the progression of gastric cancer by reprogramming amino acid metabolism through the mTOR/ASNS axis. Cancer gene therapy 12 37542132
2022 An intractable epilepsy phenotype of ASNS novel mutation in two patients with asparagine synthetase deficiency. Clinica chimica acta; international journal of clinical chemistry 12 35469797
2024 METTL3 Inhibition Suppresses Cell Growth and Survival in Colorectal Cancer via ASNS Downregulation. Journal of Cancer 11 39132158
2020 Rapid exome sequencing and adjunct RNA studies confirm the pathogenicity of a novel homozygous ASNS splicing variant in a critically ill neonate. Human mutation 11 32906196
2024 ATF4 inhibits tumor development and mediates p-GCN2/ASNS upregulation in colon cancer. Scientific reports 10 38844625
2021 ASNS disruption shortens CTPS cytoophidia in Saccharomyces cerevisiae. G3 (Bethesda, Md.) 10 33561249
2021 Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma. Frontiers in oncology 10 34540668
2024 Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures for Lcn13, Asns, Hamp2, Hao2, and Pgc1a. Journal of the Endocrine Society 9 38370444
2020 A novel compound heterozygous missense mutation in ASNS broadens the spectrum of asparagine synthetase deficiency. Molecular genetics & genomic medicine 9 32255274
2013 Dynamic changes in genomic histone association and modification during activation of the ASNS and ATF3 genes by amino acid limitation. The Biochemical journal 9 22978410
2019 Cyst-Peritoneal Shunt for the Treatment of a Progressive Intracerebral Cyst Associated with ASNS Mutation: Case Report and Literature Review. World neurosurgery 7 30844524
2025 GPS2 confers l-asparaginase resistance in acute lymphoblastic leukemia cells through ATF4/ASNS axis. Carcinogenesis 4 40693356
2023 Case report: A compound heterozygous mutations in ASNS broadens the spectrum of asparagine synthetase deficiency in the prenatal diagnosis. Frontiers in pediatrics 4 37900678
2025 CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis. Journal of experimental & clinical cancer research : CR 3 40781327
2023 Utility of ASNS gene methylation evaluated with the HPLC method as a pharmacogenomic biomarker to predict asparaginase sensitivity in BCP-ALL. Epigenetics 3 37839090
2025 Identification of 1,2,3,4,6-O-Pentagalloylglucose as a novel ASNS inhibitor for MASLD amelioration in mice by increasing l-aspartate levels alongside LKB1/AMPK metabolic axis activation. International immunopharmacology 2 40409103
2024 A novel variant in ASNS gene responsible for syndromic intellectual disability and microcephaly: Case report and literature review. Molecular genetics & genomic medicine 2 38546112
2023 A method for measurement of human asparagine synthetase (ASNS) activity and application to ASNS protein variants associated with ASNS deficiency. Biology methods & protocols 2 37965492
2025 ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression. BioFactors (Oxford, England) 1 41293996
2024 Targeting the NCAPD3 gene activates EGFR and ASNS as two pivotal contributors to gastric cancer progression. Gastroenterology and hepatology from bed to bench 1 40406431
2026 Molecular interplay of ASNS and the PI3K-AKT-mTOR pathway in CMV and HIV co-infections: Therapeutic implications. PloS one 0 41719286
2026 Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways. International journal of biological sciences 0 41943831
2026 METTL1-mediated m7G modification of ASNS mRNA regulates asparagine metabolism reprogramming to promote hepatocellular carcinoma progression. Oncogene 0 42045536
2025 Asparagine synthetase (ASNS) Drives Tumorigenicity in Small Cell Lung Cancer. Biomedicines 0 41463097
2024 Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker. Frontiers in immunology 0 39445026
2022 Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase ( ASNS ) Gene. Journal of pediatric genetics 0 38567172
2020 Congenital microcephaly with early onset epileptic encephalopathy caused by ASNS gene mutation: A case report. Medicine 0 32481472
2011 [Preparation of anti-ASNS monoclonal antibody and detection of ASNS expression in tumor]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 21208570

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