Affinage

G6PD

Glucose-6-phosphate 1-dehydrogenase · UniProt P11413

Length
515 aa
Mass
59.3 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

G6PD is the rate-limiting enzyme of the pentose phosphate pathway, catalyzing the oxidation of glucose-6-phosphate to 6-phosphoglucono-δ-lactone with concomitant reduction of NADP+ to NADPH, thereby governing cellular redox homeostasis, nucleotide biosynthesis, and lipid synthesis (PMID:4405605, PMID:32393898). Its catalytic activity requires homodimerization and is activated by phosphorylation at Y112 by c-Src and Y437 by JAK2, by SIRT2-mediated deacetylation at K403 and K171, by SIRT5-mediated deglutarylation, and by O-GlcNAcylation under hypoxia, while it is inhibited by K403 acetylation (which distorts the dimer interface and triggers downstream ubiquitylation and apoptotic signaling), arginine methylation at R246 by BHMT, direct binding of PTEN (which blocks dimerization), and scaffolding by Aldob in complex with p53 (PMID:33686238, PMID:37949355, PMID:27586085, PMID:37798264, PMID:26399441, PMID:38679670, PMID:24352616, PMID:35122041). Protein turnover is controlled by VHL-mediated ubiquitylation at K366/K403 leading to proteasomal degradation, and mRNA levels are regulated by Nrf2-dependent transcription, Sp1-mediated promoter activation, miR-122 targeting of the 3′-UTR, and ALKBH5-dependent m6A demethylation that stabilizes G6PD mRNA (PMID:30785802, PMID:26583321, PMID:24805191, PMID:29904144, PMID:34297301). Hereditary G6PD deficiency causes hemolytic anemia, with clinical severity determined by a trade-off between catalytic efficiency and protein stability dictated by variant location relative to the structural NADP+ binding site (PMID:4405605, PMID:25407525, PMID:28297664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1973 High

    The first mechanistic explanation for why some G6PD variants cause chronic hemolysis was established: hemolytic variants have high Km for NADP+ and low Ki for NADPH, rendering them functionally inactive under physiologic metabolite concentrations, whereas non-hemolytic variants retain sufficient activity to maintain glutathione.

    Evidence In vitro enzyme kinetics under simulated physiologic conditions with intermediate metabolites

    PMID:4405605

    Open questions at the time
    • Structural basis for differential kinetic parameters not yet resolved
    • In vivo erythrocyte metabolite concentrations estimated, not directly measured
  2. 1996 Medium

    The minimal cis-regulatory region sufficient for tissue-appropriate G6PD expression was defined, showing that a compact 20-kb genomic construct with 2.5 kb upstream recapitulates endogenous tissue-to-tissue expression variation via mRNA steady-state control.

    Evidence Transgenic mouse expressing human G6PD genomic construct, Northern blot and activity assays across tissues

    PMID:8964507

    Open questions at the time
    • Specific transcription factor binding sites within the 2.5 kb promoter not mapped
    • Chromatin context effects in transgene integration not controlled
  3. 2013 High

    A direct non-metabolic mechanism for G6PD regulation was uncovered: the tumor suppressor PTEN physically binds G6PD and prevents formation of the catalytically active dimer, establishing that protein–protein interactions can directly gate PPP flux independently of canonical phosphatase activity.

    Evidence Reciprocal co-immunoprecipitation, biochemical dimer assay, PPP flux measurement, knockdown

    PMID:24352616

    Open questions at the time
    • Structural details of PTEN–G6PD interface unknown
    • Whether PTEN regulates G6PD in non-hepatic tissues not tested
  4. 2014 High

    The structure–phenotype relationship underlying G6PD deficiency clinical severity was systematically resolved: mutations in the structural NADP+ binding region ablate stabilization by NADP+, producing thermolabile Class I (chronic hemolysis) variants, whereas other mutations allow NADP+-dependent stabilization and milder phenotypes.

    Evidence Recombinant variant characterization with thermostability and kinetic assays

    PMID:25407525 PMID:28297664

    Open questions at the time
    • Crystal structures of Class I variants not obtained to confirm local unfolding
    • In vivo half-life measurements in erythrocytes not performed
  5. 2014 Medium

    An epigenetic handle for G6PD transcription was identified: HDAC inhibitors selectively upregulate G6PD among PPP genes by promoting Sp1 recruitment, histone acetylation, and RNA Pol II loading at the G6PD promoter, restoring activity in patient-derived G6PD-deficient cells.

    Evidence ChIP assay at G6PD promoter, HDAC inhibitor treatment, G6PD activity in patient B cells and erythroid precursors

    PMID:24805191

    Open questions at the time
    • Which specific HDAC isoform(s) repress G6PD not identified
    • Clinical applicability of HDAC inhibitor rescue not tested in vivo
  6. 2015 High

    Two new regulatory layers were added: O-GlcNAcylation activates G6PD under hypoxia to fuel PPP-dependent biosynthesis and tumor growth, while Nrf2-dependent transcription (via HBx-p62-Keap1 sequestration) induces G6PD expression, linking metabolic stress sensors to G6PD output.

    Evidence MS-identified O-GlcNAc site with mutagenesis and xenograft validation; Co-IP of HBx-p62-Keap1 complex with Nrf2 reporter and G6PD activity

    PMID:26399441 PMID:26583321

    Open questions at the time
    • Specific O-GlcNAcylation site(s) on G6PD not fully mapped across all conditions
    • Whether Nrf2-driven G6PD induction operates beyond HBV-infected hepatocytes unclear
  7. 2016 High

    A coherent deacylation-activation axis was established: SIRT2 deacetylates G6PD at K403 and SIRT5 deglutarylates G6PD, both activating NADPH production; HSPB1 enhances the SIRT2–G6PD interaction, revealing that acylation is a major inhibitory code and sirtuins are key activators.

    Evidence In vitro deacetylation/deglutarylation assays, K403 mutagenesis, SIRT5 KO with NADPH/GSH readouts, HSPB1 Co-IP in glioma cells

    PMID:27113762 PMID:27586085 PMID:27711253

    Open questions at the time
    • Whether SIRT2 and SIRT5 act on the same G6PD pool or in distinct compartments not resolved
    • Relative contribution of deacetylation vs. deglutarylation in vivo unknown
  8. 2019 High

    Proteolytic control of G6PD was defined: VHL E3 ligase ubiquitylates G6PD at K366 and K403 for proteasomal degradation under high glucose, directly linking nutrient excess to G6PD protein loss, NADPH depletion, and oxidative injury in podocytes.

    Evidence Co-IP, ubiquitylation assay, K366/K403 mutagenesis, proteasome inhibitor rescue

    PMID:30785802

    Open questions at the time
    • Whether VHL-mediated degradation operates in non-renal tissues not examined
    • Interplay between VHL ubiquitylation at K403 and SIRT2 deacetylation at K403 not addressed
  9. 2020 High

    G6PD was established as essential for immune effector function: pharmacological inhibition with G6PDi-1 depletes NADPH most severely in lymphocytes, suppressing inflammatory cytokine production in T cells and respiratory burst in neutrophils, revealing cell-type-specific dependence on G6PD.

    Evidence Cell-active inhibitor G6PDi-1 with deuterium tracer validation of on-target activity, cytokine and ROS measurements in primary immune cells

    PMID:32393898

    Open questions at the time
    • In vivo immune phenotype of G6PD inhibition not tested
    • Whether adaptive immune responses beyond cytokine secretion are affected unknown
  10. 2020 High

    An inhibitory scaffold mechanism was revealed: Aldob directly binds G6PD (independently of its own catalytic activity) and potentiates p53-mediated G6PD inhibition within a ternary complex; liver-specific Aldob knockout promotes tumorigenesis through unleashed G6PD activity.

    Evidence GST pulldown, enzymatic mutant of Aldob, Aldob KO mouse with G6PD pharmacological rescue

    PMID:35122041

    Open questions at the time
    • Structural basis of Aldob–G6PD–p53 ternary complex unknown
    • Whether Aldob regulates G6PD outside the liver not examined
  11. 2021 High

    Two activating kinase–substrate relationships were identified: c-Src phosphorylates G6PD at Y112 (improving catalytic efficiency by lowering Km), and TSP50 promotes SIRT2-dependent deacetylation at K171, each independently boosting PPP flux and tumor cell proliferation.

    Evidence In vitro kinase assay and Y112 mutagenesis with detailed kinetics; LC-MS/MS identification of K171 with GST pulldown and xenograft validation

    PMID:33630390 PMID:33686238

    Open questions at the time
    • Whether Y112 and K171 modifications are coordinated or independent not tested
    • Phosphatase reversing Y112 phosphorylation not identified
  12. 2021 Medium

    Post-transcriptional regulation of G6PD mRNA was defined: ALKBH5 demethylates m6A on G6PD mRNA to stabilize it, promoting translation in glioma, while miR-122 directly targets the 3′-UTR to suppress G6PD expression in hepatocellular carcinoma.

    Evidence m6A-qRT-PCR and mRNA stability assays; luciferase reporter with G6PD 3′-UTR for miR-122 binding sites

    PMID:29904144 PMID:34297301

    Open questions at the time
    • m6A writer responsible for G6PD mRNA methylation (METTL14 vs others) not validated in this context
    • Whether miR-122 and m6A modifications interact on the same mRNA molecule unknown
  13. 2023 High

    A PTM crosstalk hierarchy centered on K403 acetylation was resolved: site-specific acetylation at K403 distorts the dimer interface and active site, triggers downstream ubiquitylation at K95/K97 and phosphorylation at Y503, induces p53 interaction, and initiates apoptosis — while JAK2-mediated Y437 phosphorylation under IL-6 stimulation activates G6PD for nucleotide biosynthesis, and BHMT-catalyzed R246 methylation inhibits activity.

    Evidence Genetically encoded site-specific acetylation with crystallography and PTM crosstalk MS; in vitro JAK2 kinase assay with Y437 mutagenesis and xenograft; R246 mutagenesis with methylation-specific antibody and HCC mouse model

    PMID:37798264 PMID:37949355 PMID:38679670

    Open questions at the time
    • How the cell prioritizes competing PTMs at overlapping sites (K403 acetylation vs ubiquitylation vs deacetylation) is not resolved
    • Whether R246 methylation by BHMT occurs in tissues beyond liver not tested
    • Structural basis of Y437 phosphorylation effect on substrate binding not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include how the numerous activating and inhibitory PTMs are integrated in space and time within a single cell, whether tissue-specific PTM profiles explain the selective vulnerability of erythrocytes versus cancer cells, and the structural basis for several regulatory protein–protein interactions (PTEN, Aldob, BAG3).
  • No systems-level quantitative model of PTM integration on G6PD exists
  • Structural basis of PTEN–G6PD, Aldob–G6PD, and BAG3–G6PD interfaces unresolved
  • In vivo stoichiometry and dynamics of competing modifications at K403 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 1 R-HSA-5357801 Programmed Cell Death 1
Partners
ALDOBBHMTJAK2PTENSIRT2SIRT5SRCVHL

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1973 G6PD variants causing chronic hemolytic anemia have high Michaelis constants for NADP and low inhibition constants for NADPH, making them strongly inhibited by physiologic NADPH concentrations and more sensitive to ATP inhibition under simulated physiologic conditions; non-hemolytic variants have low Km for NADP and high Ki for NADPH, retaining >30% physiologic activity sufficient to maintain glutathione levels. In vitro enzyme kinetics under simulated physiologic conditions with intermediate metabolites and co-enzymes Science High 4405605
2013 PTEN protein directly binds G6PD and prevents formation of the active G6PD dimer, thereby inhibiting PPP flux; Tcl1 reverses PTEN's effect by promoting G6PD activity and hnRNPK-dependent G6PD pre-mRNA splicing; PTEN also forms a complex with hnRNPK to inhibit G6PD pre-mRNA splicing. Co-immunoprecipitation, biochemical dimer assay, PPP flux measurement, knockdown experiments, mass spectrometry Gut High 24352616
2015 G6PD is dynamically modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to hypoxia; O-GlcNAcylation activates G6PD enzymatic activity and increases glucose flux through the PPP, providing nucleotide and lipid precursors and NADPH for antioxidant defense; blocking glycosylation reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Mass spectrometry identification of O-GlcNAc site, mutagenesis, in vitro enzyme activity assay, glucose flux tracing, xenograft tumor model Nature Communications High 26399441
2016 SIRT5 deglutarylates G6PD, activating its NADPH-producing activity; knockdown or knockout of SIRT5 leads to inhibition of G6PD, decreased NADPH, lower GSH, and increased cellular ROS susceptibility. Co-immunoprecipitation, in vitro deacylation assay, SIRT5 knockdown/knockout with NADPH and GSH measurements EMBO Reports High 27113762
2016 SIRT2 deacetylates G6PD at lysine 403 (K403), activating its enzymatic activity and promoting NADPH production to support leukaemia cell proliferation; chemical inhibitors of SIRT2 suppress G6PD activity. Site-directed mutagenesis of K403, co-immunoprecipitation, in vitro deacetylation assay, G6PD activity measurement, leukaemia cell proliferation assays Scientific Reports High 27586085
2016 HSPB1 (Hsp27) enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD, thereby sustaining cellular NADPH and pentose production in glioma cells. Co-immunoprecipitation, G6PD activity assay, NADPH measurement, HSPB1 overexpression/knockdown PLoS One Medium 27711253
2017 PAK4 interacts with G6PD and increases its activity via enhancing Mdm2-mediated p53 ubiquitination and degradation, since p53 normally inhibits G6PD; this pathway promotes glucose intake, NADPH production, and lipid biosynthesis in colon cancer cells. Co-immunoprecipitation, G6PD activity assay, ubiquitination assay, PAK4 overexpression/knockdown Cell Death & Disease Medium 28542136
2019 The VHL E3 ubiquitin ligase directly binds G6PD and ubiquitylates it at K366 and K403, promoting proteasomal degradation; high glucose conditions increase this ubiquitination without affecting G6PD mRNA, reducing G6PD protein and activity, causing ROS accumulation and podocyte injury. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis at K366 and K403, proteasome inhibitor experiments, G6PD activity assay FASEB Journal High 30785802
2019 Small molecule AG1 activates G6PD by promoting oligomerization to catalytically competent forms via a noncovalent interaction bridging the dimer interface at the structural NADP+ binding sites of two interacting G6PD monomers. Biochemical activity assay, structure-activity relationship analysis, mutagenesis of dimer interface ChemMedChem Medium 31183991
2020 Aldolase B (Aldob) directly binds G6PD and inhibits its enzymatic activity independently of Aldob's own enzymatic activity; Aldob also potentiates p53-mediated inhibition of G6PD within an Aldob-G6PD-p53 complex; global or liver-specific Aldob knockout promotes tumorigenesis through enhanced G6PD activity and PPP flux. Co-immunoprecipitation, GST pulldown, G6PD activity assay, Aldob enzymatic mutant, knockout mouse model, pharmacological G6PD inhibition Nature Cancer High 35122041
2020 A specific small-molecule inhibitor G6PDi-1 directly inhibits G6PD activity in cells, depleting NADPH most strongly in lymphocytes; in T cells, G6PD inhibition markedly decreases inflammatory cytokine production; in neutrophils, it suppresses respiratory burst, defining G6PD as required for immune effector functions. Metabolite reporter and deuterium tracer assays for cellular G6PD activity, G6PDi-1 treatment in primary immune cells, cytokine and ROS measurements Nature Chemical Biology High 32393898
2021 c-Src tyrosine kinase interacts with and phosphorylates G6PD at Tyr112; this phosphorylation enhances G6PD catalytic activity by decreasing Km for glucose-6-phosphate and increasing Kcat, augmenting PPP flux for NADPH and ribose-5-phosphate production to support tumor cell biosynthesis. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis of Y112, enzyme kinetics, flux analysis Oncogene High 33686238
2021 TSP50 binds G6PD in the cytoplasm and activates G6PD activity by inhibiting acetylation at the K171 site; TSP50 promotes binding of G6PD to SIRT2 to facilitate K171 deacetylation and activation; K171 acetylation of G6PD is required for TSP50-induced cell proliferation and tumor formation. LC-MS/MS, co-immunoprecipitation, GST pulldown, site-specific mutagenesis of K171, G6PD activity assay, in vivo xenograft model Cell Proliferation High 33630390
2021 BAG3 directly interacts with G6PD and suppresses PPP flux and de novo DNA synthesis in hepatocellular carcinoma cells; enforced G6PD expression rescues the growth defect from BAG3 elevation; BAG3 effect is nucleoside-dependent rather than NADPH-dependent. Co-immunoprecipitation, G6PD overexpression rescue, PPP flux assay, nucleoside supplementation Oncotarget Medium 26621836
2023 Acetylation of G6PD at K89 activates enzymatic activity while acetylation at K403 inhibits it; K403 acetylation causes structural distortion of the dimer interface and active site; K403 acetylation also promotes K95/97 ubiquitylation and Y503 phosphorylation of G6PD, induces interaction with p53, and triggers early apoptotic events; a single lysine acetylation coordinates multiple downstream PTMs and apoptotic signaling. Site-specifically acetylated G6PD protein (genetic code expansion), in vitro enzyme activity assay, X-ray crystallography/structural studies, mass spectrometry for PTM crosstalk, p53 co-immunoprecipitation, apoptosis assays Nature Communications High 37798264
2023 JAK2 phosphorylates G6PD at Y437 under IL-6 treatment, accentuating G6PD enzymatic activity by promoting G6PD binding with its substrate glucose-6-phosphate; JAK2-dependent Y437 phosphorylation is required for IL-6-induced nucleotide biosynthesis and tumor cell proliferation. Immunoprecipitation, in vitro kinase assay, site-directed mutagenesis of Y437, G6PD activity assay, BrdU proliferation assay, xenograft model Molecular Metabolism High 37949355
2023 Quercetin directly binds to G6PD and competitively inhibits its enzymatic activity by abrogating NADP+ binding in the catalytic domain; this reduces intracellular NADPH, causing insufficient substrate for methionine sulfoxide reductase A (MsrA) to reduce M790 oxidation of EGFR T790M, inducing EGFR T790M degradation. Direct binding assay (surface plasmon resonance or equivalent), competitive inhibition kinetics, NADPH measurement, mechanistic mutagenesis, cellular EGFR degradation assays Cell Reports Medium 37950872
2024 BHMT (betaine-homocysteine methyltransferase) methylates G6PD at arginine residue 246; this arginine methylation inhibits G6PD enzymatic activity; BHMT deficiency reduces R246 methylation of G6PD, activating G6PD and PPP metabolism to promote hepatocarcinogenesis. Co-immunoprecipitation, specific antibody against methylated G6PD, site-directed mutagenesis of R246, G6PD activity assay, proteomics, DEN-induced HCC mouse model, AAV rescue experiment Science China Life Sciences High 38679670
2014 G6PD variants with severe clinical phenotypes (Class I) remain thermolabile upon structural NADP+ addition and have mutations in the structural NADP+ binding region, whereas Class II/III variants become more thermostable with NADP+; the location of mutations determines a trade-off between catalytic activity and protein stability that underlies clinical severity. Recombinant protein expression, thermal stability (T50) assay, kinetic characterization (kcat), structural NADP+ binding assessment International Journal of Molecular Sciences High 25407525
2017 Clinical phenotype of G6PD variants is largely determined by a trade-off between protein stability and catalytic activity; bioinformatic and biochemical analysis of known variants predicts molecular phenotype of uncharacterized variants; structural nicotinamide adenine dinucleotide phosphate binding region variants particularly affect stability. Bioinformatic structural analysis, recombinant protein biochemical characterization, multidimensional analysis of kinetics and thermostability across multiple variants Cell Reports High 28297664
1996 A 20-kb human G6PD genomic construct including only 2.5 kb upstream and 2.0 kb downstream flanking sequence is sufficient to drive tissue-appropriate, regulated expression of human G6PD in transgenic mice comparable to endogenous murine G6PD, with tissue-to-tissue variation determined by mRNA steady-state levels. Transgenic mouse generation, Northern blot, enzyme activity assay across tissues Gene Medium 8964507
2021 FDX1 (ferredoxin 1) interacts with G6PD and reduces its protein stability, decreasing G6PD activity; reduced G6PD activity lowers NADPH and GSH levels, thereby enhancing cuproptosis in endometriosis cells. Co-immunoprecipitation, G6PD activity assay, NADPH/GSH measurement, cell viability assay, mouse model Apoptosis Medium 37119432
2021 ALKBH5, an m6A eraser, demethylates G6PD mRNA and enhances its stability, thereby promoting G6PD translation and activating the pentose phosphate pathway in glioma cells. m6A-qRT-PCR, mRNA stability assay, ALKBH5 gain/loss-of-function, Western blot, PPP activity measurement Neurochemical Research Medium 34297301
2021 PIKE-A binds STAT3 and stimulates its phosphorylation via tyrosine kinase Fyn, which enhances transcription of G6PD, promoting PPP flux and glioblastoma growth. Co-immunoprecipitation, kinase assay, G6PD promoter reporter assay, G6PD activity measurement, xenograft model Biochemical Pharmacology Medium 34411567
2021 G6PD deficiency in brown adipocytes causes excessive cytosolic ROS accumulation, leading to ERK activation and impaired thermogenic gene expression; antioxidant treatment or ERK inhibition restores thermogenic function in G6PD-deficient mice exposed to cold. G6PD-deficient mutant mouse model, cold exposure, ROS measurement, ERK activity assay, antioxidant/ERK inhibitor treatment, thermogenic gene expression Diabetes Medium 34521642
2015 HBV X protein (HBx) associates with the UBA and PB1 domains of p62 and augments p62-Keap1 interaction, forming an HBx-p62-Keap1 complex in the cytoplasm that sequesters Keap1 from Nrf2, leading to Nrf2 activation and consequent transcriptional upregulation of G6PD. Co-immunoprecipitation, domain mapping, Nrf2 reporter assay, G6PD activity assay, HBx overexpression Cell Death & Disease Medium 26583321
2018 miR-122 directly suppresses G6PD expression by binding to two conserved functional sites in the 3'-UTR of G6PD mRNA; ectopic expression of miR-122 and miR-1 coordinately repress G6PD expression and reduce G6PD activity in HCC cells. Luciferase reporter assay with G6PD 3'-UTR, G6PD activity assay, miRNA overexpression in HCC cells Scientific Reports Medium 29904144
2014 HDAC inhibitors selectively enhance transcription of G6PD (among all 16 glycolytic/PPP pathway genes) by increasing Sp1 recruitment to the G6PD promoter, promoting histone acetyltransferase/deacetylase recruitment, histone acetylation, and RNA polymerase II loading; this restores G6PD enzymatic activity in B cells and erythroid precursors from G6PD-deficient patients. ChIP assay, promoter analysis, HDAC inhibitor treatment, G6PD activity assay in patient-derived cells Blood Medium 24805191

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1973 Hemolytic anemia and G6PD deficiency. Science (New York, N.Y.) 237 4405605
2016 SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO reports 232 27113762
2015 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nature communications 214 26399441
2005 Diagnosis and management of G6PD deficiency. American family physician 211 16225031
2016 G6PD protects from oxidative damage and improves healthspan in mice. Nature communications 196 26976705
2013 G6PD deficiency: global distribution, genetic variants and primaquine therapy. Advances in parasitology 181 23384623
1996 G6PD: population genetics and clinical manifestations. Blood reviews 171 8861278
2020 A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway. Nature chemical biology 155 32393898
2013 G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests. Malaria journal 134 24188096
2013 Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malaria journal 120 24228846
2015 Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation. Cell death & disease 117 26583321
2013 PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis. Gut 110 24352616
2016 SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation. Scientific reports 101 27586085
2017 Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers. The American journal of tropical medicine and hygiene 98 28749773
2018 Primaquine-induced haemolysis in females heterozygous for G6PD deficiency. Malaria journal 95 29499733
2020 Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nature cancer 87 35122041
2011 Alternative targeting of Arabidopsis plastidic glucose-6-phosphate dehydrogenase G6PD1 involves cysteine-dependent interaction with G6PD4 in the cytosol. The Plant journal : for cell and molecular biology 78 21309870
2022 Recent findings in the regulation of G6PD and its role in diseases. Frontiers in pharmacology 77 36091812
2020 G6PD: A hub for metabolic reprogramming and redox signaling in cancer. Biomedical journal 76 33097441
2020 G6PD overexpression protects from oxidative stress and age-related hearing loss. Aging cell 61 33222382
2018 The role of miR-122 in the dysregulation of glucose-6-phosphate dehydrogenase (G6PD) expression in hepatocellular cancer. Scientific reports 61 29904144
2018 Modulation of G6PD affects bladder cancer via ROS accumulation and the AKT pathway in vitro. International journal of oncology 61 30066842
2014 The stability of G6PD is affected by mutations with different clinical phenotypes. International journal of molecular sciences 61 25407525
2003 Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Malays. Human mutation 60 12497642
2011 Prevalence and distribution of glucose-6-phosphate dehydrogenase (G6PD) variants in Thai and Burmese populations in malaria endemic areas of Thailand. Malaria journal 58 22171972
2017 G6PD plays a neuroprotective role in brain ischemia through promoting pentose phosphate pathway. Free radical biology & medicine 57 28823591
2016 What has passed is prolog: new cellular and physiological roles of G6PD. Free radical research 55 27684214
2017 PAK4 regulates G6PD activity by p53 degradation involving colon cancer cell growth. Cell death & disease 52 28542136
2023 FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis : an international journal on programmed cell death 48 37119432
2017 Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities. Genes & diseases 48 30258923
2006 Exercise-induced oxidative stress in G6PD-deficient individuals. Medicine and science in sports and exercise 45 16888458
2010 Rapid and reliable detection of glucose-6-phosphate dehydrogenase (G6PD) gene mutations in Han Chinese using high-resolution melting analysis. The Journal of molecular diagnostics : JMD 44 20203002
2011 G6PD up-regulation promotes pancreatic beta-cell dysfunction. Endocrinology 43 21248143
1983 Brief report: linkage between G6PD and fragile-X syndrome. American journal of medical genetics 43 6602550
2016 HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation. PloS one 42 27711253
2021 ALKBH5 Promotes the Proliferation of Glioma Cells via Enhancing the mRNA Stability of G6PD. Neurochemical research 41 34297301
2015 SMYD1 and G6PD modulation are critical events for miR-206-mediated differentiation of rhabdomyosarcoma. Cell cycle (Georgetown, Tex.) 40 25644430
2017 Modelling primaquine-induced haemolysis in G6PD deficiency. eLife 39 28155819
2019 High glucose-induced ubiquitination of G6PD leads to the injury of podocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 30785802
2017 A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency. International journal of biological macromolecules 37 28583873
1992 Molecular heterogeneity underlying the G6PD Mediterranean phenotype. Human genetics 36 1551674
2021 G6PD Variants and Haemolytic Sensitivity to Primaquine and Other Drugs. Frontiers in pharmacology 35 33790795
2017 Coupling between Protein Stability and Catalytic Activity Determines Pathogenicity of G6PD Variants. Cell reports 35 28297664
1979 The effect of BCNU and adriamycin on normal and G6PD deficient erythrocytes. American journal of hematology 34 539595
2007 Present status of understanding on the G6PD deficiency and natural selection. Journal of postgraduate medicine 31 17699998
2021 The ethnogeographic variability of genetic factors underlying G6PD deficiency. Pharmacological research 30 34551338
2023 Inhibiting G6PD by quercetin promotes degradation of EGFR T790M mutation. Cell reports 29 37950872
1996 Molecular characterization of G6PD deficiency in Oman. Human heredity 29 8860013
2009 Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population. Malaria journal 28 19589177
1996 Multiple G6PD mutations are associated with a clinical and biochemical phenotype similar to that of G6PD Mediterranean. Blood 28 8611726
2023 The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers. International journal of molecular sciences 27 38139067
2021 TSP50 promotes hepatocyte proliferation and tumour formation by activating glucose-6-phosphate dehydrogenase (G6PD). Cell proliferation 27 33630390
2019 Small-Molecule Activators of Glucose-6-phosphate Dehydrogenase (G6PD) Bridging the Dimer Interface. ChemMedChem 27 31183991
2016 BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas. Oncotarget 26 26621836
2021 c-Src facilitates tumorigenesis by phosphorylating and activating G6PD. Oncogene 25 33686238
2018 The gene spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangdong province, China. Gene 25 30077011
2013 3'-UTR variations and G6PD deficiency. Journal of human genetics 25 23389243
2019 MicroRNA-206 regulates cell proliferation by targeting G6PD in skeletal muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 31675481
2006 Contrasting histories of G6PD molecular evolution and malarial resistance in humans and chimpanzees. Molecular biology and evolution 24 16751255
2002 Identification of G6PD Mediterranean mutation by amplification refractory mutation system. Clinica chimica acta; international journal of clinical chemistry 24 12031591
2020 The vitamin B6-regulated enzymes PYGL and G6PD fuel NADPH oxidases to promote skin inflammation. Developmental and comparative immunology 23 32126244
2023 Pan-cancer analysis of G6PD carcinogenesis in human tumors. Carcinogenesis 22 37335542
2019 Impact of G6PD status on red cell storage and transfusion outcomes. Blood transfusion = Trasfusione del sangue 22 31385801
2014 Transcriptional and epigenetic basis for restoration of G6PD enzymatic activity in human G6PD-deficient cells. Blood 22 24805191
2021 PIKE-A promotes glioblastoma growth by driving PPP flux through increasing G6PD expression mediated by phosphorylation of STAT3. Biochemical pharmacology 21 34411567
2019 Prevalence and distribution of G6PD deficiency: implication for the use of primaquine in malaria treatment in Ethiopia. Malaria journal 21 31590661
2001 G6PD deficiency, distribution and variants in Saudi Arabia: an overview. Annals of Saudi medicine 21 17264545
2023 Acetylation-dependent coupling between G6PD activity and apoptotic signaling. Nature communications 20 37798264
2022 Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres. Journal of neuro-oncology 19 36396930
2020 LncRNA SNHG14 contributes to the progression of NSCLC through miR-206/G6PD pathway. Thoracic cancer 19 32153123
2001 DNA damage and apoptosis in mononuclear cells from glucose-6-phosphate dehydrogenase-deficient patients (G6PD Aachen variant) after UV irradiation. Journal of leukocyte biology 19 11261779
1999 Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Chinese. Human mutation 19 10502785
2012 Glucose-6-phosphate dehydrogenase (G6PD) gene mutations detection by improved high-resolution DNA melting assay. Molecular biology reports 18 23275194
2022 Prevalence of G6PD deficiency and G6PD variants amongst the southern Thai population. PeerJ 17 36248708
2020 COXIV and SIRT2-mediated G6PD deacetylation modulate ROS homeostasis to extend pupal lifespan. The FEBS journal 17 33058529
2019 Thalassemia trait and G6PD deficiency in Thai blood donors. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 16 30922678
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2022 Myostatin Deficiency Enhances Antioxidant Capacity of Bovine Muscle via the SMAD-AMPK-G6PD Pathway. Oxidative medicine and cellular longevity 12 35663205
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2024 RORα inhibits gastric cancer proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity. Cancer cell international 11 38184549
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