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FLASH GENE
Symbol G6PD contributors: mct - updated : 05-05-2020
HGNC name glucose-6-phosphate dehydrogenase
HGNC id 4057
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Lymphoid/Immunelymph node   moderately
 tonsils   highly
Nervousnervecranial nerve  moderately
Reproductivefemale systembreastmammary gland moderately
 male systemprostate  moderately
Respiratorylung   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  predominantly
cell lineage
cell lines
fluid/secretion highly in blood
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
coding region divided into twelve segments
conjugated PhosphoP , Other
mono polymer homomer , dimer , tetramer
HOMOLOGY
interspecies homolog to rattus G6pdx (93.6 pc)
homolog to murine G6pdx (93.6 pc)
Homologene
FAMILY glucose-6-phosphate dehydrogenase family
CATEGORY enzyme
SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular
intracellular,cytoplasm,cytosolic
intracellular,nucleus
basic FUNCTION
  • first step of pentose phosphate, pathway mainly involved in the defense against oxidizing agents through NADPH production
  • producing pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power
  • decline in the activities of G6PD and CYB5R3 would indicate a decrease in the antioxidant response associated to Red blood cell (RBC) aging
  • plays an important role in beta-cell function and survival
  • is a reduced nicotinamide adenine dinucleotide phosphate-producing enzyme that plays a key role in cellular reduction/oxidation regulation
  • G6PD is highly regulated by many signals that affect transcription, post-translation, intracellular location, and interactions with other protein
  • catalyzes the first step of the pentose phosphate pathway, and in erythrocytes, the functionality of the pathway is crucial to protect these cells against oxidative damage
  • activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells
  • plays likely an essential role in anti-oxidative defense through producing NADPH
  • is a rate-limiting enzyme of the pentose phosphate pathway
  • ultimately plays a critical role in macrophage functions used against infectious agent
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
  • carbohydrate degradation
  • pentose phosphate pathway
  • a component
  • acetylation
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • NADP
  • protein
  • :
  • G6PD activity and membrane association are regulated by SRC-mediated tyrosine phosphorylation, which contributes to VEGFA-mediated cellular responses in endothelial cell (EC)
  • SRSF3 and SRSF4 bound to the G6PD exonic splicing enhancer (ESE) in exon 12 of the mRNA
  • deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403)
  • SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation
  • mechanistically, PAK4 interacted with G6PD, a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing MDM2-mediated TP53 ubiquitination degradation
  • cell & other
    REGULATION
    activated by heat shock (40°C-42&
    8239;°C) that increased GSH levels, expression of glucose transporter SLC2A1, and enzymatic activity and expression of G6PD, the rate-limiting enzyme in the pentose cycle
    ASSOCIATED DISORDERS
    corresponding disease(s) G6PDD
    related resource Favismresearchpapers
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    is a poor prognostic factor in bladder cancer, and the levels of G6PD expression increase with increasing tumor stage
    constitutional       loss of function
    significant age-dependent decrease in G6PD activity
    constitutional       gain of function
    restores redox balance in endothelial cells exposed to high glucose, which is a potentially important therapeutic target to protect ECs from the deleterious effects of high glucose
    constitutional       gain of function
    up-regulation of G6PD in pancreatic beta-cells would induce beta-cell dysregulation through ROS accumulation in the development of type 2 diabetes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • G6PD may be a novel predictive prognostic marker for lung adenocarcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    regulation of macrophages via modulation of G6PDH activity appears to provide a novel window for those seeking to develop alternative therapies for the treatment of leishmaniasis
    cancerurinary 
    6-aminonicotinamide (6-AN), a competitive G6PD inhibitor, may be a potential therapy for bladder cancer, particularly in cases with high G6PD expression
    neurologyacquired 
    G6PD may be considered as potential therapeutic target for treatment of ischemic brain injury
    cancerdigestivecolon
    PAK4 and/or G6PD blockage might be a potential therapeutic strategy for colon cancer
    ANIMAL & CELL MODELS
  • G6pd-deficient mice had smaller islets and impaired glucose tolerance compared with control mice, which suggests that G6pd deficiency per se leads to beta-cell dysfunction and death