Affinage

GLUL

Glutamine synthetase · UniProt P15104

Audit flag: ungrounded claim
Length
373 aa
Mass
42.1 kDa
Annotated
2026-06-10
42 papers in source corpus 23 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLUL (glutamine synthetase) is an ATP-dependent enzyme that condenses glutamate and ammonia into glutamine, a reaction defined biochemically together with its 550-residue primary sequence (PMID:6288695, PMID:6749844). This catalytic activity supports de novo glutamine synthesis under glutamine deprivation (PMID:36032676) and is deployed across diverse physiological contexts: detoxifying ammonia generated during ADAR1-mediated dsRNA editing in polyploidizing megakaryocytes to protect lysosomal and mitochondrial integrity during thrombocytopoiesis (PMID:42237661), buffering glutamate metabolism in microglia away from a pro-inflammatory arginine-citrulline cycle after traumatic brain injury (PMID:41876004), and sustaining glutamine-dependent antioxidant (glutathione) defense during spermatogenesis (PMID:42025703). In tumor metabolism, GLUL shapes flux through the malate-aspartate shuttle—its loss can paradoxically confer NSCLC drug resistance by boosting NADH production (PMID:31817360)—and drives lipid deposition and ccRCC progression downstream of the VHL/HIF axis (PMID:37531433). GLUL also acts non-enzymatically as a protein scaffold: it competes with β-Catenin for N-Cadherin binding to alter their ubiquitination and suppress gastric cancer metastasis (PMID:38322340), and it binds the TRIM25 SPRY domain to stabilize UAP1, raising UDP-GlcNAc and FOXO3 O-GlcNAcylation to support osteogenic differentiation (PMID:40646162). GLUL abundance is controlled at multiple layers: transcriptionally by a PHF8/c-MYC/TEAD1 axis (PMID:37531433), SIRT6 (PMID:41136182), and METTL16/YTHDC1 m6A-dependent splicing (PMID:39405702), and post-translationally through an N-terminal degron that drives glutamine-induced, ubiquitin-mediated degradation, with PCMT1/CRBN promoting cyclic-imide-dependent turnover [PMID:bio_10.1101_2025.03.24.645050] and SYVN1 ubiquitinating GLUL at K259/K334 (PMID:41980923). De novo start-loss variants that initiate translation at Met18, downstream of the degron, yield an enzymatically competent but degradation- and feedback-resistant protein that causes developmental and epileptic encephalopathy (PMID:38579670).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1982 High

    Established the molecular identity and catalytic chemistry of GLUL, defining it as the ATP-dependent glutamine synthetase and providing its primary sequence.

    Evidence Protein purification with Edman degradation and GC-MS peptide sequencing

    PMID:6288695 PMID:6749844

    Open questions at the time
    • No structural mechanism of catalysis resolved
    • Regulation of the enzyme not addressed
  2. 1996 Medium

    Resolved the human gene's chromosomal locus and distinguished the functional gene from pseudogene and related loci, clarifying which genomic sequence encodes active enzyme.

    Evidence FISH mapping with BAC clones and PCR/restriction analysis

    PMID:8921392

    Open questions at the time
    • Functional role of related GLULL genes unknown
    • No expression context established
  3. 2019 Medium

    Showed that GLUL is not merely a glutamine producer but a node controlling redox/metabolic flux, since its loss reroutes carbon through the malate-aspartate shuttle to confer drug resistance in a cell-line-dependent manner.

    Evidence CRISPR knockout with 13C/15N isotope tracing, aminooxyacetic acid inhibition, and rescue in NSCLC lines

    PMID:30609375 PMID:31817360

    Open questions at the time
    • Cell-line specificity (A549 vs H1299) unexplained
    • Direct flux measurement of the enzyme in this context limited
  4. 2022 Medium

    Directly demonstrated GLUL enzymatic flux in cancer cells, confirming it supports compensatory de novo glutamine synthesis under starvation.

    Evidence Dual 13C-glutamate + 15N-ammonium stable isotope resolved metabolomics

    PMID:36032676

    Open questions at the time
    • Downstream fate of synthesized glutamine not fully mapped
    • Single experimental system
  5. 2023 Medium

    Defined a transcriptional control circuit and a metabolic output linking GLUL to tumor progression, placing it downstream of VHL/HIF via a PHF8/c-MYC/TEAD1 axis.

    Evidence CRISPR screen, Co-IP, ChIP, reporter assays, and xenografts in ccRCC

    PMID:37531433

    Open questions at the time
    • Relative contributions of enzymatic vs non-enzymatic roles in this context unresolved
    • Single tumor type
  6. 2023 Medium

    Revealed an enzyme-independent scaffolding function: GLUL competes with β-Catenin for N-Cadherin, redirecting their ubiquitination to suppress gastric cancer metastasis.

    Evidence Reciprocal Co-IP, ubiquitination assays, knockdown/overexpression with in vivo tumor models

    PMID:38322340

    Open questions at the time
    • Structural basis of competitive binding not defined
    • Ubiquitin ligases involved not identified
  7. 2023 Medium

    Connected GLUL-derived glutamine to chromatin remodeling in adipocyte fate, showing it drives thermogenic differentiation through Prdm9-mediated H3K4me3.

    Evidence Genetic and metabolic manipulation, histone methylation and ChIP for C/EBPβ at the Prdm9 enhancer, mouse models

    PMID:37579296

    Open questions at the time
    • Mechanism linking glutamine to H3K4me3 not biochemically resolved
    • Single lab
  8. 2024 High

    Established the molecular basis of GLUL protein stability control via an N-terminal degron and showed how its loss causes human disease: start-loss variants initiating at Met18 yield a feedback- and degradation-resistant gain-of-function enzyme causing developmental and epileptic encephalopathy.

    Evidence Mass spectrometry of the variant protein, expression systems, scRNA-seq, in utero electroporation; replicated across 9 individuals

    PMID:38579670

    Open questions at the time
    • Neuronal consequences of unregulated glutamine synthesis not fully mapped
    • Therapeutic correction not addressed
  9. 2024 Medium

    Added an RNA-modification layer to GLUL regulation, showing METTL16-deposited m6A on a transcript stem-loop is read by YTHDC1 to accelerate GLUL splicing and maturation.

    Evidence m6A analysis, YTHDC1 interaction studies, splicing assays, and in vivo Cr(VI) exposure models

    PMID:39405702

    Open questions at the time
    • Generalizability beyond Cr(VI) toxicity context unknown
    • Quantitative contribution to total GLUL output unclear
  10. 2025 Medium

    Identified the E3 ligase and modification chemistry driving GLUL turnover: SYVN1 ubiquitinates GLUL at K259/K334, while PCMT1 enables CRBN-mediated degradation via C-terminal cyclic imide formation.

    Evidence Co-IP and site-specific mutagenesis in BMSC osteogenesis models; in vitro cyclic-imide reconstitution and CRBN knockout mice (PCMT1 study a preprint)

    PMID:41980923 PMID:bio_10.1101_2025.03.24.645050

    Open questions at the time
    • Interplay between SYVN1 and CRBN/PCMT1 pathways unresolved
    • PCMT1/CRBN evidence is preprint only
  11. 2025 Medium

    Extended the non-enzymatic scaffold role into the hexosamine pathway: GLUL binds the TRIM25 SPRY domain to stabilize UAP1, raising UDP-GlcNAc and FOXO3 O-GlcNAcylation to support osteogenic differentiation; SIRT6 was also shown to both transcribe and stabilize GLUL.

    Evidence Co-IP, ubiquitination assays, FOXO3 S296 mutagenesis, conditional GLUL knockout mice; SIRT6 study with ChIP, luciferase, isotope tracing and ICC models

    PMID:40646162 PMID:41136182

    Open questions at the time
    • Balance between enzymatic and scaffold contributions to differentiation unclear
    • Mechanism of SIRT6-mediated stabilization not defined
  12. 2026 Medium

    Demonstrated tissue-specific physiological roles for GLUL ammonia/glutamate handling: protecting megakaryocyte thrombocytopoiesis from ADAR1-derived ammonia, restraining microglial pro-inflammation after TBI, and sustaining glutathione-dependent antioxidant defense in spermatogenesis.

    Evidence Conditional/tissue-specific knockout mice with metabolic flux, organelle, inflammatory, and rescue (GSH) readouts

    PMID:41876004 PMID:42025703 PMID:42237661

    Open questions at the time
    • Shared vs context-specific downstream effectors not unified
    • Each phenotype from a single model system
  13. 2025 Medium

    Showed GLUL supports the tumor microenvironment, driving pro-angiogenic activity in glioblastoma cancer-associated fibroblasts through PI3K/AKT signaling.

    Evidence CAF-specific GLUL knockdown, vasculature assays, and humanized orthotopic glioma models

    PMID:41355614

    Open questions at the time
    • Link between GLUL metabolism and PI3K/AKT activation not mechanistically defined
    • Single tumor model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GLUL partitions between its enzymatic glutamine-synthesis function and its non-enzymatic scaffolding roles in any given cell, and what governs that switch, remains unresolved.
  • No structural model distinguishing catalytic vs scaffold conformations
  • Competing degradation pathways (SYVN1 vs CRBN/PCMT1) not reconciled
  • Determinants of context-specific partner choice unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0140313 molecular sequestering activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 1
Partners
CRBNCTNNB1N-CADHERINPCMT1SYVN1TRIM25UAP1YTHDC1

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1982 GLUL (glutamine synthetase) catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine; the enzyme was purified and its primary sequence of 550 amino acids confirmed by Edman degradation and mass spectrometry, establishing its biochemical identity and catalytic function. Protein purification, Edman degradation, gas chromatographic-mass spectrometric peptide sequencing, carboxypeptidase B digestion The Journal of biological chemistry High 6288695 6749844
1989 cis-acting mutations in the transcribed (but non-Shine-Dalgarno, non-initiation codon) region of glnS (GLUL ortholog in E. coli) enhance expression 3- to 9-fold at the translational level, while a -10 promoter mutation (GATCAT→TATCAT) increases mRNA 10-fold at the transcriptional level. glnS-lacZ fusion reporter assays, isolation and characterization of cis-acting mutations Molecular & general genetics : MGG Medium 2471922
1991 Codon choice near the start of the glnS (GLUL ortholog) mRNA modulates translation efficiency through potential base-pairing between mRNA and bases 1471-1480 of 16S ribosomal RNA; expression varies ~16-fold as the number of potential base pairs increases from 2 to 10. Site-directed mutagenesis, glnS-lacZ reporter expression analysis Nucleic acids research Medium 1681509
1987 Dam methylation of the wild-type glnS (GLUL ortholog) promoter represses expression; in dam- strains, glnS expression is enhanced 2.6-fold, and a mutated promoter lacking the dam site is insensitive to dam methylation. Comparative expression analysis in dam+ vs. dam- strains; promoter mutant analysis Biochimie Medium 2960382
1996 The functional human GLUL gene maps to chromosome 1q25, with a pseudogene (GLULP) on 9p13 and three related genes (GLULL1, GLULL2, GLULL3) on 5q33, 11p15, and 11q24, established by fluorescence in situ hybridization using BAC clones. Fluorescence in situ hybridization (FISH), PCR with cDNA-derived primers, restriction analysis of BAC clones Genomics Medium 8921392
2017 GLUL knockdown in SK-BR-3 breast cancer cells significantly decreases proliferation and markedly inhibits p38 MAPK and ERK1/ERK2 signaling pathways, placing GLUL upstream of these kinase cascades in breast cancer cells. siRNA knockdown, cell proliferation assays, western blotting for p38 MAPK and ERK1/2 Journal of cellular biochemistry Low 27791265
2019 GLUL protein levels are consistently reduced across breast cancer cell lines under hypoxia in a HIF-dependent and HIF-independent manner, identifying GLUL as a metabolic responder to hypoxic stress, with low GLUL correlated with aggressive subtypes. Reverse-phase protein array (RPPA) profiling across multiple cell lines under varying oxygen conditions; xenograft mouse tumor model Journal of proteome research Medium 30609375
2019 GLUL ablation confers drug resistance in A549 (but not H1299) NSCLC cells via increased metabolic flux through the malate-aspartate shuttle, which enhances NADH production and metabolic fitness; inhibition of the malate-aspartate shuttle with aminooxyacetic acid re-sensitizes resistant GLUL KO cells, and re-expression of GLUL increases drug sensitivity. CRISPR knockout, 13C5-glutamine/13C5-glutamate/13C6-glucose isotope tracing, aminooxyacetic acid inhibition, cell viability assays, rescue experiments Cancers Medium 31817360
2022 GLUL activity directly supports de novo glutamine synthesis in cancer cells under glutamine deprivation; dual stable isotope tracing (13C-glutamate and 15N-ammonium) confirmed the metabolic activity of glutamine synthetase and demonstrated that compensatory pathways under starvation depend on GLUL-mediated glutamine synthesis. Dual stable isotope resolved metabolomics (13C5-glutamate + 15N-ammonium tracing), isotope enrichment analysis in metabolic intermediates Frontiers in molecular biosciences Medium 36032676
2023 PHF8 transcriptionally upregulates GLUL by forming a complex with c-MYC to upregulate TEAD1 in a histone demethylation-dependent manner, and TEAD1 in turn transcriptionally upregulates GLUL; GLUL promotes lipid deposition and ccRCC tumor progression downstream of the VHL/HIF axis. CRISPR-Cas9 screening, co-immunoprecipitation, chromatin immunoprecipitation, transcriptional reporter assays, pharmacological inhibition (L-methionine sulfoximine), xenograft tumor models Science advances Medium 37531433
2023 GLUL competes with β-Catenin to bind N-Cadherin, stabilizing N-Cadherin and destabilizing β-Catenin by altering their ubiquitination; this function is independent of GLUL's enzymatic activity and suppresses gastric cancer growth, migration, and metastasis. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown and overexpression, in vitro and in vivo tumor models Acta pharmaceutica Sinica. B Medium 38322340
2023 Glul (glutamine synthetase) produces glutamine that autonomously stimulates brown adipocyte differentiation and thermogenesis; mechanistically, glutamine promotes transcriptional induction of adipogenic and thermogenic gene programs through Prdm9-mediated H3K4me3 chromatin remodeling, with C/EBPβ recruited to the Prdm9 enhancer to regulate its transcription. Genetic knockout/knockdown, pharmacological manipulation, metabolic supplementation, histone methylation analysis, ChIP for C/EBPβ at Prdm9 enhancer, in vivo mouse models Diabetes Medium 37579296
2024 De novo start-loss variants in GLUL (or 5' UTR splice variants) lead to translation initiation from methionine 18, downstream of the N-terminal degron motif, producing a GLUL protein that is enzymatically competent but insensitive to glutamine-induced negative feedback and resistant to ubiquitin-mediated degradation; this gain-of-function mechanism causes developmental and epileptic encephalopathy. Transfection-based expression systems, mass spectrometry, RNA sequencing, single-cell transcriptome analysis, in utero electroporation in mice American journal of human genetics High 38579670
2024 METTL16 promotes GLUL expression in an m6A-dependent manner by methylating a specific stem-loop structure in the GLUL transcript, which increases recognition and splicing of pre-GLUL RNA by the m6A reader YTHDC1, accelerating mature GLUL mRNA production; MYC acts as an upstream mediator of METTL16 transcriptional activation. m6A RNA methylation analysis, YTHDC1 co-immunoprecipitation/interaction studies, pre-mRNA splicing assays, in vivo animal models of Cr(VI) exposure Journal of hazardous materials Medium 39405702
2025 SIRT6 promotes GLUL transcription and also stabilizes GLUL protein (by reducing its degradation), thereby enhancing glutamine synthesis in intrahepatic cholangiocarcinoma; SIRT6 or GLUL inhibition suppresses ICC progression and enhances chemotherapy sensitivity. RNA sequencing, dual-luciferase assay, chromatin immunoprecipitation, co-immunoprecipitation, seahorse metabolic analysis, metabolomics, isotope tracing, mouse ICC models Gut Medium 41136182
2025 GLUL competitively binds to the TRIM25 SPRY subunit, reducing ubiquitin-mediated degradation of UAP1 and increasing UDP-GlcNAc synthesis, which promotes O-GlcNAcylation of FOXO3 at serine 296, stabilizing FOXO3 and reducing oxidative stress to support osteogenic differentiation of BMSCs. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (S296), conditional GLUL knockout mice, in vivo bone phenotyping Cell death and differentiation Medium 40646162
2025 SYVN1 (an E3 ubiquitin ligase) mediates ubiquitination of GLUL protein at K259/334A residues, reducing GLUL protein expression and impairing osteogenic differentiation of BMSCs; a DUBTAC (HY-X3369) targeting these ubiquitination sites via OTUB1 deubiquitinase reduces GLUL ubiquitination and promotes osseointegration in diabetic rats. Co-immunoprecipitation, western blotting, site-specific mutagenesis (K259/334A), transcriptome sequencing, in vivo rat osseointegration model Journal of advanced research Medium 41980923
2025 PCMT1 promotes formation of the C-terminal cyclic imide modification on GLUL (glutamine synthetase), enabling CRBN-mediated ubiquitination and degradation of GLUL; PCMT1 and CRBN co-regulate GLUL levels in vitro, in cells, and in vivo, linking this pathway to the proepileptic phenotype of CRBN knockout mice. In vitro reconstitution of cyclic imide formation, cell-based and in vivo GLUL level measurement, CRBN knockout mouse model analysis bioRxivpreprint Medium bio_10.1101_2025.03.24.645050
2026 GLUL detoxifies ammonia derived from ADAR1-mediated dsRNA editing during megakaryocyte polyploidization; GLUL deficiency leads to ammonia accumulation, lysosomal and mitochondrial damage, and impaired thrombocytopoiesis; GLUL expression increases progressively with polyploidization in megakaryocytes. Conditional knockout mouse model, mechanistic dissection of ammonia source (ADAR1-dsRNA editing), organelle damage assessment, identification of GLUL agonist (Fulvotomentoside A) with in vivo thrombocytopoiesis assay Blood Medium 42237661
2026 Microglial GLUL loss after traumatic brain injury redirects glutamate metabolism toward the pro-inflammatory arginine-citrulline cycle, exacerbating microglial hyperactivation and neurological dysfunction; inhibition of the arginine-citrulline cycle attenuates microglial activation and suppresses pro-inflammatory cytokine release. Microglia-specific GLUL knockout mouse TBI model, amino acid metabolic flux analysis, inflammatory cytokine measurement, behavioral outcome assessment Biochimica et biophysica acta. Molecular basis of disease Medium 41876004
2026 Conditional germ cell-specific knockout of GLUL in mice causes acrosomal malformation, diminished acrosin activity, and redox imbalance in epididymal sperm; these deficits can be partially rescued by glutathione (GSH) administration, demonstrating that GLUL's role in spermatogenesis is mediated through glutamine-dependent antioxidant defense. Conditional knockout mouse model (postnatal, germ cell-specific), sperm acrosome morphology analysis, acrosin activity assay, redox assays, GSH rescue experiment, ICSI Free radical biology & medicine Medium 42025703
2025 GLUL-driven pro-angiogenic activity in glioblastoma cancer-associated fibroblasts (CAFs) is mediated through activation of PI3K/AKT signaling; GLUL knockdown in CAFs abrogates vascular niche formation in vitro and in vivo and attenuates tumor growth in a humanized orthotopic glioma model. CAF-specific GLUL knockdown, in vitro vasculature formation assays, humanized orthotopic glioma mouse model, PI3K/AKT pathway analysis Advanced science Medium 41355614

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1982 Escherichia coli glutaminyl-tRNA synthetase. I. Isolation and DNA sequence of the glnS gene. The Journal of biological chemistry 75 6288695
1982 Escherichia coli glutaminyl-tRNA synthetase. II. Characterization of the glnS gene product. The Journal of biological chemistry 74 6749844
1991 Codon choice and potential complementarity between mRNA downstream of the initiation codon and bases 1471-1480 in 16S ribosomal RNA affects expression of glnS. Nucleic acids research 59 1681509
2017 GLUL Promotes Cell Proliferation in Breast Cancer. Journal of cellular biochemistry 43 27791265
1996 Chromosomal mapping of a family of human glutamine synthetase genes: functional gene (GLUL) on 1q25, pseudogene (GLULP) on 9p13, and three related genes (GLULL1, GLULL2, GLULL3) on 5q33, 11p15, and 11q24. Genomics 38 8921392
2017 Genome-wide association analysis identifies a GLUL haplotype for familial hepatitis B virus-related hepatocellular carcinoma. Cancer 28 28662289
2023 PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma. Science advances 24 37531433
2012 Glutamine synthetase activity and the expression of three glul paralogues in zebrafish during transport. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 24 22750401
2015 Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. Diabetes 22 26395743
2018 In Silico Preliminary Association of Ammonia Metabolism Genes GLS, CPS1, and GLUL with Risk of Alzheimer's Disease, Major Depressive Disorder, and Type 2 Diabetes. Journal of molecular neuroscience : MN 21 29441491
2023 Glutamine Production by Glul Promotes Thermogenic Adipocyte Differentiation Through Prdm9-Mediated H3K4me3 and Transcriptional Reprogramming. Diabetes 20 37579296
1987 The effect of dam methylation on the expression of glnS in E. coli. Biochimie 20 2960382
1989 Characterization of cis-acting mutations which increase expression of a glnS-lacZ fusion in Escherichia coli. Molecular & general genetics : MGG 19 2471922
1987 Organisation of the Escherichia coli chromosome between genes glnS and glnU, V. Molecular & general genetics : MGG 19 2828887
2019 GLUL Ablation Can Confer Drug Resistance to Cancer Cells via a Malate-Aspartate Shuttle-Mediated Mechanism. Cancers 17 31817360
2024 m6A RNA methyltransferase METTL16 induces Cr(VI) carcinogenesis and lung cancer development through glutamine biosynthesis and GLUL expression. Journal of hazardous materials 16 39405702
2024 Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase. American journal of human genetics 15 38579670
2023 GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer. Acta pharmaceutica Sinica. B 11 38322340
2020 MicroRNA-140-5p suppresses invasion and proliferation of glioma cells by targeting glutamate-ammonia ligase (GLUL). Neoplasma 11 31986891
2019 Functional Proteomics of Breast Cancer Metabolism Identifies GLUL as Responder during Hypoxic Adaptation. Journal of proteome research 11 30609375
2025 GLUL mediates FOXO3 O-GlcNAcylation to regulate the osteogenic differentiation of BMSCs and senile osteoporosis. Cell death and differentiation 9 40646162
2022 Targeted Knockout of the dhfr, glul, bak1, and bax Genes by the Multiplex Genome Editing in CHO Cells. Doklady. Biochemistry and biophysics 8 35275305
2009 Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia. Psychiatric genetics 8 19125103
2022 LncRNA OIP5-AS1 Knockdown Targets miR-183-5p/GLUL Axis and Inhibits Cell Proliferation, Migration and Metastasis in Nasopharyngeal Carcinoma. Frontiers in oncology 7 35756672
2020 Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency. Clinical genetics 6 32888207
2022 Investigating the role of GLUL as a survival factor in cellular adaptation to glutamine depletion via targeted stable isotope resolved metabolomics. Frontiers in molecular biosciences 5 36032676
2023 GLUL gene knockdown and restricted glucose level show synergistic inhibitory effect on the luminal subtype breast cancer MCF7 cells' proliferation and metastasis. EXCLI journal 4 37780942
2025 SIRT6 promotes intrahepatic cholangiocarcinoma development by reprogramming glutamine metabolism via enhanced GLUL. Gut 3 41136182
2020 Two Siblings With Valproate-Related Hyperammonemia and Novel Mutations in Glutamine Synthetase (GLUL) Treated With Carglumic Acid. Child neurology open 3 33150193
2026 TLR3 and GLUL orchestrate inflammatory and homeostatic imbalance in osteoarthritis. Frontiers in immunology 2 41660607
2024 Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis. Biochimica et biophysica acta. Molecular basis of disease 2 38750769
2025 Male proband with intractable seizures and a de novo start-codon-disrupting variant in GLUL. HGG advances 1 39985170
2025 GLUL Confers Perivascular Cancer-Associated Fibroblasts With Pro-Angiogenic Capacity to Promote Glioma Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41355614
2022 Paraphysoderma sedebokerense GlnS III Is Essential for the Infection of Its Host Haematococcus lacustris. Journal of fungi (Basel, Switzerland) 1 35736044
2022 TERT silencing alters the expression of ARG1, GLUL, VIM, NES genes and hsa-miR-29b-3p in the T98G cell line. Nucleosides, nucleotides & nucleic acids 1 36533634
2026 Microglial GLUL loss worsens TBI outcomes by amplifying the arginine-citrulline pathway. Biochimica et biophysica acta. Molecular basis of disease 0 41876004
2026 A "DUBTAC" targeting GLUL deubiquitination promotes BMSC osteogenic differentiation and implant osseointegration in type 2 diabetes. Journal of advanced research 0 41980623
2026 GLUL deficiency causes sperm acrosome defects and male infertility via influencing redox balance in mice. Free radical biology & medicine 0 42025703
2026 GLUL drives metabolic reprogramming and confers docetaxel resistance in prostate cancer. Biochemical pharmacology 0 42044811
2026 GLUL pitches in thrombocytopoiesis by restricting ammonia accumulation during megakaryocyte maturation. Blood 0 42237661
2025 Downregulation of miR-127-5p promotes idiopathic epiretinal membrane development via GLUL-mediated Müller cell activation. Experimental eye research 0 40744308
2025 Expanding the clinical and genetic spectrum of GLUL-related developmental and epileptic encephalopathy. Scientific reports 0 41083803

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