Affinage

G6PD

Glucose-6-phosphate 1-dehydrogenase · UniProt P11413

Length
515 aa
Mass
59.3 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

G6PD is the rate-limiting enzyme of the pentose phosphate pathway, oxidizing glucose-6-phosphate to generate NADPH and ribose-5-phosphate that drive redox homeostasis, nucleotide and lipid biosynthesis, and cell survival (PMID:26399441, PMID:15271799). Catalysis requires assembly of inactive monomers into active dimers, and a recurring theme across the literature is that this dimerization step is the regulatory fulcrum: stability and activity trade off through mutations at the dimer interface and structural NADP+ site, where the most severe clinical variants destabilize the enzyme while catalytic-residue mutations reduce activity without destabilization (PMID:28297664, PMID:25407525). A dense network of post-translational modifications tunes dimer formation in opposite directions. Inhibitory inputs include acetylation at K403, which structurally distorts the dimer interface and active site to abolish activity (reversed by the deacetylase SIRT2) (PMID:24769394, PMID:27586085, PMID:37798264), glutarylation (reversed by SIRT5) (PMID:27113762), arginine methylation at R246 controlled by BHMT (PMID:38679670), and VHL-mediated ubiquitination at K366/K403 that targets G6PD for proteasomal degradation (PMID:30785802). Activating inputs include O-GlcNAcylation under hypoxia (PMID:26399441), tyrosine phosphorylation at Y112 by c-Src and Y437 by JAK2 that improve substrate binding and kinetics (PMID:33686238, PMID:37949355), and CDK5 phosphorylation at T91 that promotes dimer assembly under oxidative stress (PMID:40370560). G6PD activity is further set by direct protein partners that govern the dimer: PTEN, Aldolase B (acting as a scaffold with p53), BAG3, and FDX1 each bind G6PD and suppress its activity or stability, whereas HSPB1 and TSP50 promote its SIRT2-dependent activation (PMID:24352616, PMID:35122041, PMID:27711253, PMID:33630390, PMID:37119432, PMID:26621836). Expression is independently set at the transcriptional and post-transcriptional level by Sp1/chromatin acetylation, NF-κB p65/pSTAT3, Nrf2 (engaged by HBV HBx), and m6A regulators ALKBH5, METTL14, and IGF2BP2 (PMID:24805191, PMID:33041664, PMID:26583321, PMID:34297301, PMID:39138186). Functionally, G6PD-derived NADPH is indispensable for definitive erythropoiesis, preventing apoptosis of definitive erythrocytes (PMID:15271799), and for limiting protein glutathionylation and ROS-driven damage (PMID:17516514, PMID:34521642). Across cancers these regulatory inputs converge to elevate PPP flux supporting proliferation (PMID:26399441, PMID:33686238, PMID:37949355).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2004 High

    Establishing that G6PD-derived NADPH is not merely housekeeping but specifically required for a defined developmental program addressed why the enzyme is physiologically essential.

    Evidence G6PD-null ES cell differentiation in embryoid bodies with apoptosis assays and rescue by reducing agents, caspase inhibitors, and G6PD re-expression

    PMID:15271799

    Open questions at the time
    • Does not define which downstream NADPH-dependent process protects definitive erythrocytes
    • Primitive erythropoiesis tolerance mechanism not explained
  2. 2008 Medium

    Linking G6PD deficiency to loss of redox buffering connected enzyme activity to a concrete protein-protective output.

    Evidence G6PD-deficient vs wild-type cells under oxidant challenge with glutathionylation, Ku DNA-binding, and NADPH/GSH readouts plus gene rescue

    PMID:17516514

    Open questions at the time
    • Generality beyond Ku not established
    • Single cell-line pair
  3. 2013 High

    Identifying PTEN as a direct binder that blocks active-dimer formation revealed that protein-protein interactions, not just substrate supply, gate PPP flux.

    Evidence Co-IP, mass spectrometry, PPP flux measurements, and epistasis with the Tcl1/hnRNPK splicing axis

    PMID:24352616

    Open questions at the time
    • Structural basis of dimer blockade not resolved
    • Quantitative contribution versus PTEN's phosphatase functions unclear
  4. 2014 High

    Pinpointing K403 acetylation as a dimer-disrupting inhibitory mark reversed by SIRT2 defined the first PTM switch controlling G6PD activity.

    Evidence Acetylation-mimetic mutants, in vitro activity assays, Co-IP, and rescue in cells and mouse erythrocytes with SIRT2 depletion

    PMID:24769394

    Open questions at the time
    • Physiological acetyltransferase only proposed (KAT9/ELP3)
    • Stoichiometry of K403 acetylation in vivo unknown
  5. 2014 Medium

    Demonstrating selective transcriptional upregulation of G6PD by HDAC inhibitors and tissue-appropriate constitutive expression from a compact locus established how G6PD levels are set, separate from activity regulation.

    Evidence HDACi with ChIP for Sp1/histone acetylation/Pol II and enzyme rescue in patient cells; transgenic mouse with a 20-kb G6PD construct and tissue mRNA/activity quantitation

    PMID:24805191 PMID:8964507

    Open questions at the time
    • Specific regulatory elements driving tissue variation not mapped
    • Whether HDACi rescue translates clinically untested in these studies
  6. 2015 High

    Showing O-GlcNAcylation activates G6PD under hypoxia connected nutrient/stress sensing to PPP-driven biosynthesis and tumor growth.

    Evidence O-GlcNAc assays, activity assays, metabolic flux, site mutagenesis, and xenograft models

    PMID:26399441

    Open questions at the time
    • Enzymes adding/removing the modification on G6PD not identified
    • Interplay with other activating PTMs unresolved
  7. 2016 Medium

    Identifying glutarylation reversed by SIRT5 and the HSPB1-enhanced SIRT2 axis expanded the deacylation control of G6PD and showed PTM activation is scaffolded.

    Evidence SIRT5 KO/knockdown with activity, NADPH, GSH, ROS readouts; reciprocal Co-IP of HSPB1-G6PD-SIRT2 with activity assays

    PMID:27113762 PMID:27711253

    Open questions at the time
    • Glutarylation site(s) on G6PD not pinpointed
    • HSPB1 axis from a single study
  8. 2016 High

    Confirming SIRT2-mediated K403 deacetylation sustains leukemia proliferation with a tumor-selective vulnerability advanced G6PD regulation toward therapeutic relevance.

    Evidence SIRT2 knockdown, K403 mimetic mutants, activity and colony assays, SIRT2 inhibitors, and AML patient samples

    PMID:27586085

    Open questions at the time
    • Basis of selectivity for leukemic over normal cells incomplete
  9. 2016 Medium

    Finding BAG3 suppresses PPP-dependent DNA synthesis without lowering NADPH separated G6PD's biosynthetic from redox outputs.

    Evidence Co-IP, G6PD rescue overexpression, PPP flux and DNA synthesis assays, nucleoside supplementation rescue

    PMID:26621836

    Open questions at the time
    • Mechanism by which BAG3 differentially channels output unclear
    • Single lab
  10. 2017 Medium

    Defining a stability-versus-activity trade-off across clinical variants explained the structural logic of G6PD deficiency phenotypes.

    Evidence Bioinformatic structural analysis with biochemical characterization of variant stability and activity and clinical correlation

    PMID:28297664

    Open questions at the time
    • No direct timeline link to specific Mendelian disease via causative-mutation rescue
    • Predictive accuracy for novel variants not validated
  11. 2019 High

    Mapping VHL-mediated ubiquitination at K366/K403 established degradation as a control point coupling glucose load to G6PD abundance and tissue injury.

    Evidence Co-IP, ubiquitination-site mutagenesis, knockdown/overexpression rescue, and G6PD-deficient mouse kidney analysis

    PMID:30785802

    Open questions at the time
    • Crosstalk between K403 acetylation and K403 ubiquitination not resolved here
    • Signal triggering VHL recruitment to G6PD unclear
  12. 2019 Medium

    Showing a small molecule activates G6PD by bridging the structural NADP+ sites to drive dimerization validated the dimer interface as a druggable activation switch.

    Evidence Biochemical activity and oligomerization assays with SAR and dimer-interface site mapping (AG1)

    PMID:31183991

    Open questions at the time
    • Cellular and in vivo efficacy not established in this study
    • Selectivity over variant enzymes untested
  13. 2020 High

    Establishing Aldolase B as an enzymatically independent scaffold that potentiates p53-mediated G6PD inhibition added a tumor-suppressive complex to the regulatory network.

    Evidence Direct binding and Co-IP, activity assays, Aldob KO mouse with re-expression rescue, and pharmacological G6PD inhibition

    PMID:35122041

    Open questions at the time
    • How the Aldob-G6PD-p53 complex mechanically blocks dimers unresolved
  14. 2020 Medium

    Demonstrating p65/pSTAT3 cooperative transcriptional activation showed inflammatory signaling directly elevates G6PD in renal cancer.

    Evidence ChIP, Co-IP of the p65/pSTAT3 complex, luciferase reporter, and xenografts

    PMID:33041664

    Open questions at the time
    • Generality across tumor types not tested
    • Single lab
  15. 2021 High

    Identifying c-Src Y112 phosphorylation that lowers Km and raises Kcat provided a kinetic mechanism for oncogenic G6PD activation.

    Evidence Co-IP, in vitro kinase assay with Km/Kcat analysis, site mutagenesis, flux assays, and CRC sample correlation

    PMID:33686238

    Open questions at the time
    • In vivo contribution relative to other activating PTMs unclear
  16. 2021 Medium

    Convergent findings positioned G6PD-derived NADPH as a determinant of cell-death modalities (ferroptosis, cuproptosis) and brown-fat thermogenesis, broadening its physiological reach.

    Evidence G6PD knockdown with POR and ferroptosis readouts; FDX1 Co-IP with stability/NADPH/GSH and cuproptosis assays; G6PD-deficient mice with cold exposure, ROS, ERK inhibition and antioxidant rescue

    PMID:34325001 PMID:34521642 PMID:37119432

    Open questions at the time
    • G6PD-POR link not biochemically demonstrated (Low confidence)
    • Direct molecular coupling of NADPH levels to each death pathway incomplete
  17. 2021 Medium

    Showing TSP50 inhibits K171 acetylation and promotes SIRT2 binding identified an additional acetylation site and a tumor-promoting activator.

    Evidence LC-MS/MS, Co-IP, GST pull-down, K171 mutagenesis, and proliferation/tumor formation assays

    PMID:33630390

    Open questions at the time
    • K171 acetyltransferase not defined
    • Relationship to K403/K89 acetylation unresolved
  18. 2021 Medium

    Identifying ALKBH5-mediated m6A demethylation as a stabilizer of G6PD mRNA established post-transcriptional control of PPP capacity.

    Evidence m6A-qRT-PCR, ALKBH5 gain/loss-of-function, mRNA stability and activity assays

    PMID:34297301

    Open questions at the time
    • m6A sites on G6PD transcript not mapped
    • Single tumor context
  19. 2023 High

    Site-specific reconstitution distinguishing activating K89 from inhibitory K403 acetylation, with structural and downstream signaling consequences, resolved how a single PTM type produces opposite effects and links G6PD to apoptosis.

    Evidence Genetic code expansion for site-specific acetylation, structural studies, MS-based PTM analysis, p53 Co-IP, and apoptosis assays

    PMID:37798264

    Open questions at the time
    • Endogenous enzymes setting K89 versus K403 acetylation not identified
    • Physiological balance of opposing marks in tissues unknown
  20. 2023 Medium

    Defining JAK2 Y437 phosphorylation downstream of IL-6 and quercetin as a competitive NADP+-site inhibitor extended both physiological activation and pharmacological inhibition mechanisms.

    Evidence Co-IP, mutagenesis of Y437, kinetics, proliferation and xenograft assays; direct binding and competitive-inhibition kinetics for quercetin with EGFRT790M degradation

    PMID:37949355 PMID:37950872

    Open questions at the time
    • In vivo selectivity of quercetin for G6PD uncertain
    • Single lab per finding
  21. 2024 Medium

    Identifying CDK5 T91 phosphorylation as a dimer-promoting activator, BHMT-controlled R246 methylation as an inhibitor, and METTL14/IGF2BP2 m6A stabilization completed multiple converging regulatory axes feeding tumor metabolism.

    Evidence Kinase/dimerization assays and Olaparib synergy (CDK5); Co-IP, R246 mutagenesis, methyl-specific antibodies and Bhmt KO mice (BHMT); MeRIP-seq, IGF2BP2 RIP, and stability/xenograft assays (METTL14)

    PMID:38679670 PMID:39138186 PMID:40370560

    Open questions at the time
    • Hierarchy and crosstalk among the many PTM and RNA-level inputs unresolved
    • The R246 methyltransferase acting via BHMT not directly defined
    • Each axis from a single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozen-plus competing PTMs, protein partners, transcriptional and m6A inputs are integrated in a given cell to set G6PD dimer state remains the central open question.
  • No unified model of combinatorial PTM crosstalk on the dimer interface
  • Endogenous writers for several modifications (K89, K171, R246, glutarylation, O-GlcNAc) unidentified
  • Relative quantitative contribution of each regulator in normal physiology versus cancer unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ALDOBBAG3FDX1HSPB1PAK4PTENSIRT2VHL

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. K403-acetylated G6PD is incapable of forming active dimers and displays complete loss of activity. SIRT2 deacetylates K403 to activate G6PD in response to oxidative stress. KAT9/ELP3 was identified as a potential acetyltransferase of G6PD. Acetylation-mimetic mutants, in vitro enzymatic activity assays, Co-IP, knockdown/rescue experiments in cells and mouse erythrocytes, SIRT2 depletion The EMBO journal High 24769394
2016 SIRT5 deglutarylates G6PD, activating the enzyme and increasing NADPH production. Knockdown or knockout of SIRT5 leads to inhibition of G6PD activity, decreased NADPH, lowered GSH, and increased cellular susceptibility to oxidative stress. SIRT5 KO/knockdown, enzymatic activity assays, NADPH and GSH measurements, ROS quantification EMBO reports High 27113762
2015 G6PD is dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAcylation) in response to hypoxia. This glycosylation activates G6PD activity, increases glucose flux through the PPP, and promotes nucleotide/lipid biosynthesis and antioxidant defense. Blocking G6PD glycosylation reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. O-GlcNAc modification assays, enzymatic activity assays, metabolic flux analysis, glycosylation site mutagenesis, in vivo xenograft models Nature communications High 26399441
2013 PTEN protein directly binds G6PD and prevents formation of the active G6PD dimer, thereby inhibiting PPP flux. Tcl1, acting via hnRNPK, promotes G6PD pre-mRNA splicing and protein expression. PTEN also forms a complex with hnRNPK to inhibit G6PD pre-mRNA splicing. PTEN inactivates Tcl1 via GSK3β-mediated phosphorylation. Co-immunoprecipitation, mass spectrometry, molecular biology assays, PPP flux measurements, epistasis analysis Gut High 24352616
2016 SIRT2 promotes G6PD deacetylation at K403, activating G6PD to increase NADPH production and support leukaemia cell proliferation. Chemical inhibition of SIRT2 suppresses G6PD activity and reduces leukaemia cell but not normal hematopoietic cell proliferation. SIRT2 knockdown, K403 acetylation-mimetic mutants, enzymatic activity assays, colony formation assays, SIRT2 inhibitors, patient AML sample analysis Scientific reports High 27586085
2020 Aldolase B (Aldob) directly binds G6PD and inhibits its enzymatic activity, suppressing PPP metabolism. Aldob potentiates p53-mediated inhibition of G6PD by forming an Aldob-G6PD-p53 complex. This scaffolding effect is independent of Aldob enzymatic activity. Direct binding assays, Co-IP, enzymatic activity assays, Aldob KO mouse model, Aldob/G6PD re-expression rescue experiments, pharmacological G6PD inhibition Nature cancer High 35122041
2021 c-Src tyrosine kinase directly interacts with and phosphorylates G6PD at Tyr112, enhancing catalytic activity by decreasing Km and increasing Kcat for glucose-6-phosphate substrate, thereby augmenting PPP flux for NADPH and ribose-5-phosphate production. Co-IP, in vitro kinase assay, Km/Kcat kinetic analysis, site-directed mutagenesis, metabolic flux assays, clinical CRC sample correlation Oncogene High 33686238
2019 G6PD is ubiquitinated on K366 and K403 by the VHL E3 ubiquitin ligase, which directly binds G6PD, leading to G6PD proteasomal degradation under high glucose conditions and resulting in ROS accumulation and podocyte injury. Co-IP demonstrating VHL-G6PD interaction, site-directed mutagenesis of ubiquitination sites, Western blot, G6PD overexpression rescue, siRNA knockdown, G6PD-deficient mouse kidney analysis FASEB journal High 30785802
2004 G6PD is indispensable for definitive erythropoiesis after the embryonic-adult hemoglobin switch. G6PD-null ES cells differentiate normally into primitive erythroid cells but definitive erythrocytes undergo apoptosis that is prevented only by restoration of G6PD activity. G6PD-null mouse ES cell differentiation (embryoid body system), apoptosis assays, reducing agents rescue, caspase inhibitor rescue, G6PD re-expression rescue Blood High 15271799
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 response to oxidative stress or DNA damage. Co-IP, enzymatic activity assays, NADPH measurement, siRNA knockdown, HSPB1 overexpression PloS one Medium 27711253
2017 PAK4 interacts with G6PD and increases G6PD activity via enhancing Mdm2-mediated p53 ubiquitination and degradation (as p53 suppresses G6PD), thereby promoting glucose intake, NADPH production, lipid biosynthesis and colon cancer cell proliferation. Co-IP, G6PD enzymatic activity assays, metabolic measurements, p53 ubiquitination assays, siRNA knockdown, clinical correlation Cell death & disease Medium 28542136
2021 TSP50 binds G6PD in the cytoplasm and activates G6PD activity by inhibiting acetylation of G6PD at K171. TSP50 also promotes the binding of G6PD to SIRT2. K171 acetylation of G6PD is required for TSP50-induced cell proliferation and tumor formation. LC-MS/MS, Co-IP, GST pull-down, site-specific mutation of K171, enzymatic activity assays, cell proliferation and tumor formation assays Cell proliferation Medium 33630390
2023 Acetylation at K89 activates G6PD while acetylation at K403 inhibits G6PD. K403 acetylation-dependent inactivation is explained by structural distortion of the dimeric structure and active site. K403 acetylation also leads to K95/97 ubiquitylation and Y503 phosphorylation of G6PD, interaction with p53, and induction of early apoptotic events. Site-specifically acetylated G6PD via genetic code expansion, enzymatic activity assays, structural studies, mass spectrometry-based PTM analysis, p53 Co-IP, apoptosis assays Nature communications High 37798264
2019 Small molecule AG1 activates G6PD by promoting oligomerization (dimer formation) at the structural NADP+ binding sites bridging the dimer interface. The mechanism is noncovalent and the disulfide in AG1 is not required for activation. Biochemical activity assays, structure-activity relationship analysis, oligomerization assays, site mapping at dimer interface ChemMedChem Medium 31183991
2023 Quercetin directly binds G6PD and inhibits its enzymatic activity by competitively abrogating NADP+ binding in the catalytic domain, reducing intracellular NADPH and causing degradation of EGFRT790M. Direct binding assays, competitive inhibition kinetics, NADPH measurement, EGFRT790M degradation assays, cell-based studies Cell reports Medium 37950872
2021 FDX1 interacts with G6PD and reduces its protein stability, decreasing G6PD activity and NADPH/GSH levels, thereby enhancing cuproptosis in endometriosis cells. Co-IP demonstrating FDX1-G6PD interaction, G6PD stability assays, NADPH/GSH measurements, cuproptosis assays, mouse model Apoptosis Medium 37119432
2016 BAG3 directly interacts with G6PD and suppresses PPP flux and de novo DNA synthesis in hepatocellular carcinoma cells. The growth defect from BAG3 overexpression is rescued by enforced G6PD expression. BAG3 elevation did not cause reduction in cellular NADPH, indicating the inhibitory effect is specifically on nucleotide synthesis via PPP. Co-IP, G6PD rescue overexpression, PPP flux measurement, DNA synthesis assay, nucleoside supplementation rescue Oncotarget Medium 26621836
2017 G6PD variant pathogenicity is largely determined by a trade-off between protein stability and catalytic activity. Structural mutations at the dimer interface or structural NADP+ binding site cause instability and severe clinical phenotypes, while mutations affecting catalytic residues reduce activity without destabilizing the enzyme. Bioinformatic structural analysis, biochemical characterization of G6PD variants (stability, activity assays), multidimensional analysis of clinical variant data Cell reports Medium 28297664
2014 G6PD variants with different clinical phenotypes show differing protein stability. Structural rigidity underlies mutation effects on protein stability and folding. Class I (most severe) variants remain thermolabile even with increasing NADP+, whereas Class II and III variants become more thermostable with NADP+, indicating that Class I mutations affect the structural NADP+ binding region. Overexpression and purification of G6PD variants, kinetic constants (kcat), T50 thermal stability assay, protein yield analysis, NADP+ thermostabilization assays International journal of molecular sciences Medium 25407525
2008 G6PD deficiency leads to loss of cellular control of protein glutathionylation. G6PD-deficient cells show increased protein glutathionylation and loss of Ku protein function upon oxidant treatment (HEDS), due to decreased NADPH, protein thiols, and GSH. Reintroduction of the G6PD gene restores normal phenotype. Comparison of G6PD-deficient (E89) vs wild-type (K1) cells, oxidant challenge, protein glutathionylation assay (ELISA), Ku protein-DNA binding assay, NADPH/GSH measurement, G6PD rescue by gene reintroduction Journal of cellular biochemistry Medium 17516514
2021 G6PD defect in brown adipocytes impairs thermogenic function through excessive cytosolic ROS accumulation, leading to ERK activation, which suppresses thermogenic gene expression. Antioxidant treatment or ERK inhibition restores thermogenic activity in G6PD-deficient mice. G6PD-deficient mutant mice, cold exposure, ROS measurement, thermogenic gene expression analysis, ERK inhibitor treatment, antioxidant administration Diabetes Medium 34521642
2023 JAK2 phosphorylates G6PD at Y437 under IL-6 treatment, accentuating G6PD enzymatic activity by promoting G6PD binding with its substrate G6P, leading to increased PPP flux and nucleotide biosynthesis to support tumor cell proliferation. Co-IP, enzymatic activity assays, site-directed mutagenesis of Y437, BrdU proliferation assay, colony formation assay, xenograft model, patient sample correlation Molecular metabolism Medium 37949355
2024 CDK5 phosphorylates G6PD at Thr-91, facilitating assembly of inactive G6PD monomers into active dimers under oxidative stress in breast cancer cells. CDK5 inhibition abrogates G6PD phosphorylation and synergistically sensitizes breast cancer cells to PARP inhibitor Olaparib. Kinase assays, site-directed mutagenesis, dimerization assays, CDK5 inhibitors, xenograft models, patient tissue analysis Acta pharmaceutica Sinica B Medium 40370560
2024 BHMT deficiency activates G6PD by decreasing arginine methylation of G6PD at arginine 246. BHMT directly regulates methylation of G6PD, and pharmacological inhibition of G6PD attenuates BHMT-deficiency-driven hepatocarcinogenesis. Co-IP, proteomics, metabolomics, site-directed mutagenesis of R246, specific antibodies against methylated G6PD, Bhmt KO mouse models, G6PD inhibitor rescue Science China. Life sciences Medium 38679670
2014 HDAC inhibitors selectively enhance G6PD transcription among all 16 glycolytic/PPP pathway genes through enhanced recruitment of transcription factor Sp1, commensurate recruitment of histone acetyltransferases and deacetylases, increased histone acetylation, and RNA polymerase II recruitment to the G6PD locus, restoring enzymatic activity in G6PD-deficient nucleated cells. HDACi treatment, ChIP assays for Sp1/histone acetylation/Pol II, transcriptional analysis, G6PD enzymatic activity in patient B cells and erythroid precursors Blood Medium 24805191
2021 G6PD inhibits ferroptosis in hepatocellular carcinoma through cytochrome P450 oxidoreductase (POR). Knockdown of G6PD upregulates POR, which mediates the suppression of HCC cell growth and ferroptosis sensitivity. siRNA knockdown of G6PD, ferroptosis assays, POR expression analysis, in vivo xenograft tumor growth Cellular signalling Low 34325001
2020 NF-κB p65 and pSTAT3 synergistically drive G6PD overexpression in clear cell RCC. p65 directly binds the G6PD promoter, and p65/pSTAT3 form a complex that occupies the pSTAT3-binding site on the G6PD promoter to facilitate transcription. ChIP assay, Co-IP of p65/pSTAT3 complex, luciferase reporter assay, NF-κB activator/inhibitor treatment, xenograft model Cancer cell international Medium 33041664
2015 HBV X protein (HBx) stimulates G6PD expression via Nrf2 activation. HBx associates with UBA and PB1 domains of adaptor protein p62, augmenting interaction between p62 and Nrf2 repressor Keap1 to form an HBx-p62-Keap1 complex that sequesters Keap1 from Nrf2, leading to Nrf2 activation and consequent G6PD transcription. Co-IP, domain mapping, G6PD promoter analysis, Nrf2 pathway analysis, G6PD expression and activity assays in HBV-infected cells Cell death & disease Medium 26583321
2021 ALKBH5 acts as an m6A eraser that demethylates the G6PD transcript, enhancing G6PD mRNA stability and promoting G6PD translation, thereby activating the pentose phosphate pathway and supporting glioma cell proliferation. m6A-qRT-PCR, ALKBH5 gain/loss-of-function, G6PD mRNA stability assays, G6PD expression and activity analysis Neurochemical research Medium 34297301
2024 METTL14-mediated m6A modification of G6PD mRNA is recognized by IGF2BP2, which enhances G6PD mRNA stability, thereby upregulating G6PD expression post-transcriptionally and promoting lung adenocarcinoma tumor growth and metastasis. RNA sequencing, MeRIP-sequencing, METTL14 knockdown/overexpression, IGF2BP2 interaction with G6PD mRNA, G6PD expression and stability assays, in vivo xenograft model Cell death discovery Medium 39138186
1996 A 20-kb human G6PD construct containing only 2.5 kb upstream and 2.0 kb downstream flanking sequence is sufficient to drive high-level, constitutive, tissue-appropriate G6PD expression in transgenic mice, with steady-state mRNA levels accounting for tissue-to-tissue variation in enzyme activity. Transgenic mouse generation, enzyme activity assays across tissues, mRNA Northern blot Gene Medium 8964507

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. The EMBO journal 261 24769394
2016 SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO reports 234 27113762
2015 O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nature communications 216 26399441
2005 Diagnosis and management of G6PD deficiency. American family physician 212 16225031
2016 G6PD protects from oxidative damage and improves healthspan in mice. Nature communications 201 26976705
2007 G6PD deficiency: the genotype-phenotype association. Blood reviews 193 17611006
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 164 32393898
2013 G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. British journal of haematology 149 24372186
2017 Disrupting G6PD-mediated Redox homeostasis enhances chemosensitivity in colorectal cancer. Oncogene 124 28692052
2013 Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malaria journal 121 24228846
2015 Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation. Cell death & disease 118 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
2021 G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase. Cellular signalling 96 34325001
2018 Primaquine-induced haemolysis in females heterozygous for G6PD deficiency. Malaria journal 94 29499733
2020 Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nature cancer 91 35122041
2022 Recent findings in the regulation of G6PD and its role in diseases. Frontiers in pharmacology 83 36091812
2020 G6PD: A hub for metabolic reprogramming and redox signaling in cancer. Biomedical journal 77 33097441
2020 G6PD overexpression protects from oxidative stress and age-related hearing loss. Aging cell 63 33222382
2018 Modulation of G6PD affects bladder cancer via ROS accumulation and the AKT pathway in vitro. International journal of oncology 63 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
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 57 27684214
2023 FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis. Apoptosis : an international journal on programmed cell death 52 37119432
2017 PAK4 regulates G6PD activity by p53 degradation involving colon cancer cell growth. Cell death & disease 52 28542136
2019 Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017. Human mutation 51 31489982
2017 Glucose 6 phosphatase dehydrogenase (G6PD) and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities. Genes & diseases 49 30258923
2020 Targeting G6PD reverses paclitaxel resistance in ovarian cancer by suppressing GSTP1. Biochemical pharmacology 47 32535103
2006 Exercise-induced oxidative stress in G6PD-deficient individuals. Medicine and science in sports and exercise 45 16888458
2016 HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation. PloS one 44 27711253
2011 G6PD up-regulation promotes pancreatic beta-cell dysfunction. Endocrinology 44 21248143
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
1991 Definition of the mutations of G6PD Wayne, G6PD Viangchan, G6PD Jammu, and G6PD 'LeJeune'. Acta haematologica 43 1805484
2021 ALKBH5 Promotes the Proliferation of Glioma Cells via Enhancing the mRNA Stability of G6PD. Neurochemical research 41 34297301
2017 Modelling primaquine-induced haemolysis in G6PD deficiency. eLife 40 28155819
2015 SMYD1 and G6PD modulation are critical events for miR-206-mediated differentiation of rhabdomyosarcoma. Cell cycle (Georgetown, Tex.) 40 25644430
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 39 30785802
2019 G6PD deficiency: An update. JAAPA : official journal of the American Academy of Physician Assistants 39 31609781
1997 A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency. Mutation research 39 9067418
2021 G6PD Variants and Haemolytic Sensitivity to Primaquine and Other Drugs. Frontiers in pharmacology 36 33790795
1992 Molecular heterogeneity underlying the G6PD Mediterranean phenotype. Human genetics 36 1551674
2023 Inhibiting G6PD by quercetin promotes degradation of EGFR T790M mutation. Cell reports 35 37950872
2017 Coupling between Protein Stability and Catalytic Activity Determines Pathogenicity of G6PD Variants. Cell reports 35 28297664
2021 The ethnogeographic variability of genetic factors underlying G6PD deficiency. Pharmacological research 32 34551338
2007 Present status of understanding on the G6PD deficiency and natural selection. Journal of postgraduate medicine 32 17699998
2004 G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch. Blood 31 15271799
2023 The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers. International journal of molecular sciences 30 38139067
1996 Molecular characterization of G6PD deficiency in Oman. Human heredity 29 8860013
2021 TSP50 promotes hepatocyte proliferation and tumour formation by activating glucose-6-phosphate dehydrogenase (G6PD). Cell proliferation 28 33630390
2009 Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population. Malaria journal 28 19589177
2019 Small-Molecule Activators of Glucose-6-phosphate Dehydrogenase (G6PD) Bridging the Dimer Interface. ChemMedChem 27 31183991
2021 c-Src facilitates tumorigenesis by phosphorylating and activating G6PD. Oncogene 26 33686238
2016 BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas. Oncotarget 26 26621836
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
2023 Pan-cancer analysis of G6PD carcinogenesis in human tumors. Carcinogenesis 24 37335542
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
2002 Identification of G6PD Mediterranean mutation by amplification refractory mutation system. Clinica chimica acta; international journal of clinical chemistry 24 12031591
2023 Acetylation-dependent coupling between G6PD activity and apoptotic signaling. Nature communications 23 37798264
2005 G6PD--an old bottle with new wine. Chang Gung medical journal 23 16323551
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
2001 G6PD deficiency, distribution and variants in Saudi Arabia: an overview. Annals of Saudi medicine 22 17264545
2023 PBX3 promotes pentose phosphate pathway and colorectal cancer progression by enhancing G6PD expression. International journal of biological sciences 21 37781025
2020 LncRNA SNHG14 contributes to the progression of NSCLC through miR-206/G6PD pathway. Thoracic cancer 20 32153123
2022 Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres. Journal of neuro-oncology 19 36396930
2022 Prevalence of G6PD deficiency and G6PD variants amongst the southern Thai population. PeerJ 18 36248708
2020 COXIV and SIRT2-mediated G6PD deacetylation modulate ROS homeostasis to extend pupal lifespan. The FEBS journal 18 33058529
2024 The global role of G6PD in infection and immunity. Frontiers in immunology 17 38938571
2020 NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC. Cancer cell international 17 33041664
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
2015 Maintaining Specimen Integrity for G6PD Screening by Cytofluorometric Assays. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 25786434
2008 Mutation in G6PD gene leads to loss of cellular control of protein glutathionylation: mechanism and implication. Journal of cellular biochemistry 16 17516514
2022 Incorporating G6PD genotyping to identify patients with G6PD deficiency. Pharmacogenetics and genomics 15 34693927
2022 Myostatin Deficiency Enhances Antioxidant Capacity of Bovine Muscle via the SMAD-AMPK-G6PD Pathway. Oxidative medicine and cellular longevity 14 35663205
2021 Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function. Diabetes 14 34521642
2020 Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 14 33069889
2019 Molecular Characterization of G6PD Deficiency: Report of Three Novel G6PD Variants. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 14 32425388
2000 Molecular basis of haemoglobinopathies and G6PD deficiency in the Comorian population. The hematology journal : the official journal of the European Haematology Association 14 11920200
2021 Distribution of G6PD deficiency genotypes among Southeast Asian populations. Tropical medicine and health 13 34930507
2018 Cytochemical flow analysis of intracellular G6PD and aggregate analysis of mosaic G6PD expression. European journal of haematology 13 29240263
1996 High-level regulated expression of the human G6PD gene in transgenic mice. Gene 13 8964507
2024 RORα inhibits gastric cancer proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity. Cancer cell international 12 38184549
2023 IL-6/JAK2-dependent G6PD phosphorylation promotes nucleotide synthesis and supports tumor growth. Molecular metabolism 12 37949355
2024 METTL14-mediated m6A mRNA modification of G6PD promotes lung adenocarcinoma. Cell death discovery 11 39138186
2010 G6PD-MutDB: a mutation and phenotype database of glucose-6-phosphate (G6PD) deficiency. Journal of bioinformatics and computational biology 11 21155022
2024 Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis. Science China. Life sciences 10 38679670
2023 Genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangzhou, China. Human genomics 10 36949502
2023 Etiology analysis and G6PD deficiency for term infants with jaundice in Yangjiang of western Guangdong. Frontiers in pediatrics 10 37492600
2021 Discovery and characterization of a novel glucose-6-phosphate dehydrogenase (G6PD) inhibitor via high-throughput screening. Bioorganic & medicinal chemistry letters 10 33689874
2010 Discussion on pharmacogenetic interaction in G6PD deficiency and methods to identify potential hemolytic drugs. Cardiovascular & hematological disorders drug targets 10 20350285
2024 Implementation of Universal Screening for G6PD Deficiency in Newborns. Pediatrics 9 38988309
2024 CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer. Acta pharmaceutica Sinica. B 9 40370560
2022 G6PD Deficiency Is Crucial for Insulin Signaling Activation in Skeletal Muscle. International journal of molecular sciences 9 35806430
2018 Prevalence of G6PD deficiency and associated haematological parameters in children from Botswana. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 9 29778768
2018 Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and phenotype and rasburicase use in patients with hematologic malignancies. The pharmacogenomics journal 9 30206300
2015 G6PD gene variants and its association with malaria in a Sri Lankan population. Malaria journal 9 25885177

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