{ "schemaVersion": "BASE-biological-assertion/1.1.0", "caseStudy": { "slug": "g6pd-deficiency", "title": "G6PD Deficiency: Red Cells Under Oxidative Stress" }, "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "groups": [ { "id": "gene-pathway", "title": "Gene & Pathway", "description": "How G6PD connects to the pathway’s NADPH output.", "assertionIds": [ "g6pd.gene-encodes-enzyme", "g6pd.enzyme-first-oxidative-step", "g6pd.catalyzes-ppp-entry-reaction", "g6pd.oxidative-branch-produces-nadph" ] }, { "id": "red-cell-context", "title": "Red-Cell Context", "description": "Why this pathway matters in mature erythrocytes.", "assertionIds": [ "g6pd.erythrocyte-nadph-context" ] }, { "id": "antioxidant-defense", "title": "Antioxidant Defense", "description": "How NADPH and glutathione support peroxide removal.", "assertionIds": [ "g6pd.nadph-recycles-glutathione", "g6pd.glutathione-reduces-peroxide" ] }, { "id": "disease-context", "title": "Disease & Exposure Context", "description": "What the mechanism can explain—and what it cannot predict.", "assertionIds": [ "g6pd.deficiency-can-limit-redox-response", "g6pd.oxidative-exposures-and-hemolysis" ] } ], "assertions": [ { "id": "g6pd.gene-encodes-enzyme", "version": 1, "subjectId": "gene-g6pd", "predicate": "ENCODES", "objectId": "protein-g6pd", "statement": "The human G6PD gene encodes glucose-6-phosphate dehydrogenase.", "qualifier": "NCBI annotates G6PD as a protein-coding gene and lists multiple transcript/protein isoforms.", "evidenceKind": "database_annotation", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd", "relation": "supports", "sourceRecordId": "NCBI Gene:2539", "sourceVersion": "Record updated 2026-09-13" }, { "referenceId": "uniprot-g6pd", "relation": "supports", "sourceRecordId": "UniProt:P11413", "sourceVersion": "Reviewed entry; release not recorded in this snapshot" } ] }, { "id": "g6pd.enzyme-first-oxidative-step", "version": 1, "subjectId": "protein-g6pd", "predicate": "CATALYZES_STEP_IN", "objectId": "pathway-pentose-phosphate", "statement": "G6PD catalyzes the first oxidative reaction of the pentose phosphate pathway, reducing NADP+ as glucose 6-phosphate is oxidized.", "qualifier": "This is the pathway entry reaction; 6-phosphogluconate dehydrogenase also generates NADPH later in the oxidative branch.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "ncbi-g6pd", "relation": "supports", "sourceRecordId": "NCBI Gene:2539", "sourceVersion": "Record updated 2026-09-13" } ] }, { "id": "g6pd.catalyzes-ppp-entry-reaction", "version": 1, "subjectId": "protein-g6pd", "predicate": "CATALYZES_REACTION", "objectValue": { "kind": "reaction", "pathwaySlug": "pentose-phosphate", "reactionSlug": "pentose-phosphate-01", "stepNumber": 1, "name": "Oxidation of glucose 6-phosphate" }, "statement": "G6PD catalyzes the pentose-phosphate pathway's entry reaction, oxidizing glucose 6-phosphate while reducing NADP+ to NADPH.", "qualifier": "This is a selected human teaching reaction from the oxidative branch. It is not a complete representation of pathway flux or every cellular context.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336; local reaction pentose-phosphate-01", "sourceVersion": "Reactome release not recorded in this snapshot" } ] }, { "id": "g6pd.oxidative-branch-produces-nadph", "version": 1, "subjectId": "pathway-pentose-phosphate", "predicate": "GENERATES_IN_OXIDATIVE_BRANCH", "objectId": "molecule-nadph", "statement": "The oxidative branch of the human pentose phosphate pathway generates NADPH.", "qualifier": "The two oxidative dehydrogenase reactions contribute NADPH; the pathway also supplies pentose-phosphate intermediates, and net flux depends on cellular demand.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336", "sourceVersion": "Stable identifier; release not recorded in this snapshot" } ] }, { "id": "g6pd.erythrocyte-nadph-context", "version": 1, "subjectId": "cell-type-erythrocyte", "predicate": "DEPENDS_ON_FOR_NADPH", "objectId": "pathway-pentose-phosphate", "statement": "Mature human red blood cells lack mitochondria and rely on the pentose phosphate pathway for NADPH production.", "qualifier": "This statement is scoped to mature erythrocytes; it should not be generalized to nucleated cells or other tissues.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd-mgs", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.nadph-recycles-glutathione", "version": 1, "subjectId": "molecule-nadph", "predicate": "SUPPORTS_REGENERATION_OF", "objectId": "molecule-glutathione-reduced", "statement": "NADPH powers glutathione reductase to convert oxidized glutathione (GSSG) back to reduced glutathione (GSH).", "qualifier": "GSH is one part of red-cell antioxidant defense; this simplified chain does not represent every peroxide-removal or redox system.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-gsr", "relation": "supports", "sourceRecordId": "NCBI Gene:2936", "sourceVersion": "Record accessed 2026-09-27" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.glutathione-reduces-peroxide", "version": 1, "subjectId": "molecule-glutathione-reduced", "predicate": "SUPPORTS_PEROXIDE_REDUCTION", "objectId": "molecule-hydrogen-peroxide", "statement": "GPX1 can use GSH to reduce hydrogen peroxide to water, producing GSSG.", "qualifier": "GPX1 is one contributor; other antioxidant enzymes and context-specific redox processes also matter.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-gpx1", "relation": "supports", "sourceRecordId": "NCBI Gene:2876", "sourceVersion": "Record updated 2026-09-13" }, { "referenceId": "uniprot-gpx1", "relation": "supports", "sourceRecordId": "UniProt:P07203", "sourceVersion": "Entry release not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.deficiency-can-limit-redox-response", "version": 1, "subjectId": "disease-g6pd-deficiency", "predicate": "CAN_LIMIT_NADPH_RESPONSE", "objectId": "cell-type-erythrocyte", "statement": "Some G6PD variants reduce enzyme activity and can leave erythrocytes less able to replenish NADPH during an oxidative challenge.", "qualifier": "Residual activity, variant, erythrocyte age, sex and X-chromosome inactivation, exposure, and other biology affect phenotype; this is not a deterministic individual prediction.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd-mgs", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" }, { "referenceId": "g6pd-cpic-2023", "relation": "qualifies", "sourceRecordId": "CPIC guideline; PMCID:PMC10281211", "sourceVersion": "Published 2023" } ] }, { "id": "g6pd.oxidative-exposures-and-hemolysis", "version": 1, "subjectId": "disease-g6pd-deficiency", "predicate": "MAY_BE_ASSOCIATED_WITH", "objectValue": "Acute hemolysis in susceptible contexts", "statement": "Some people with G6PD deficiency can develop acute hemolysis after particular infections or oxidant exposures, including some medications.", "qualifier": "Risk differs by drug, dose, genotype, residual enzyme activity, co-exposures, and clinical state. BASE does not classify a user's medication as safe or unsafe or predict personal risk.", "evidenceKind": "clinical_guideline", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "g6pd-cpic-2023", "relation": "supports", "sourceRecordId": "CPIC guideline; PMCID:PMC10281211", "sourceVersion": "Published 2023" }, { "referenceId": "ncbi-g6pd-mgs", "relation": "qualifies", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" } ] } ], "limitation": "Educational mechanism map only. It does not diagnose G6PD deficiency or predict an individual's clinical or medication risk.", "release": { "snapshotSchemaVersion": "BASE-case-snapshot/1.0.0", "exportedAt": "2026-10-11T01:51:13.567Z", "caseContentRevision": 1, "diagramRevision": 1, "diagramId": "g6pd-red-cell-redox-map", "sourceCommitSha": "e97dc5327f9d807ecaf44b77e87ddf6f3f6d2bc2", "snapshotSha256": "ba57fa3d29c4c78ef36935de53fdf05cccd8e338dfe79747e4741c24ed3b427e" }, "snapshot": { "releaseInputs": { "caseContentRevision": 1, "diagramRevision": 1, "diagramId": "g6pd-red-cell-redox-map", "sourceCommitSha": "e97dc5327f9d807ecaf44b77e87ddf6f3f6d2bc2" }, "caseStudy": { "slug": "g6pd-deficiency", "title": "G6PD Deficiency: Red Cells Under Oxidative Stress", "area": "Genes · Metabolism · Blood", "question": "Why can some G6PD variants make red blood cells more vulnerable to oxidative stress?", "overview": "Mature red blood cells have no mitochondria. They use glycolysis to make ATP and rely on the pentose phosphate pathway for NADPH, which helps maintain antioxidant defenses. Some G6PD variants reduce enzyme activity, so a red cell may have less capacity to respond to particular oxidant challenges.", "mechanism": [ "The G6PD gene encodes glucose-6-phosphate dehydrogenase. Different variants can leave different amounts of enzyme activity; the gene name alone does not predict severity.", "G6PD catalyzes the first oxidative reaction of the pentose phosphate pathway. Together, the two oxidative dehydrogenase reactions produce NADPH.", "NADPH powers glutathione reductase, which recycles oxidized glutathione (GSSG) into reduced glutathione (GSH).", "Glutathione peroxidase can use GSH to reduce hydrogen peroxide to water, converting GSH back to GSSG.", "If an oxidant challenge exceeds a susceptible red cell's defenses, oxidative damage and hemolysis can occur. Whether and how severely this happens depends on variant, residual activity, cell age, exposure, and other context." ], "evidence": "This is a context-limited mechanism map, not a medication checker or personal risk prediction. CPIC evaluates drug-specific evidence and risk categories; infection, dose, co-exposures, genotype, and clinical state can change the context. The pathway map shows selected relationships and does not imply G6PD is the only factor in red-cell antioxidant defense.", "entityIds": [ "gene-g6pd", "protein-g6pd", "pathway-pentose-phosphate", "molecule-nadph", "protein-glutathione-reductase", "molecule-glutathione-disulfide", "molecule-glutathione-reduced", "protein-gpx1", "molecule-hydrogen-peroxide", "cell-type-erythrocyte", "process-oxidative-stress", "disease-g6pd-deficiency" ], "references": [ "reactome-pentose-phosphate", "ncbi-g6pd", "uniprot-g6pd", "ncbi-g6pd-mgs", "g6pd-redox-review", "g6pd-cpic-2023", "ncbi-gsr", "ncbi-gpx1", "uniprot-gpx1" ], "assertionIds": [ "g6pd.gene-encodes-enzyme", "g6pd.enzyme-first-oxidative-step", "g6pd.catalyzes-ppp-entry-reaction", "g6pd.oxidative-branch-produces-nadph", "g6pd.erythrocyte-nadph-context", "g6pd.nadph-recycles-glutathione", "g6pd.glutathione-reduces-peroxide", "g6pd.deficiency-can-limit-redox-response", "g6pd.oxidative-exposures-and-hemolysis" ], "check": [ { "question": "Why is NADPH especially important in a mature red blood cell?", "answer": "Mature red cells lack mitochondria and depend on the pentose phosphate pathway for NADPH. NADPH helps recycle glutathione used in antioxidant reactions." }, { "question": "Does every person with a G6PD variant have the same response to every medication or infection?", "answer": "No. Residual enzyme activity, variant, red-cell age, sex and X-chromosome inactivation, the exposure, and other clinical context affect risk. This map cannot predict an individual's response." }, { "question": "Which molecule is recycled by glutathione reductase using NADPH?", "answer": "Glutathione disulfide (GSSG) is reduced back to reduced glutathione (GSH)." } ] }, "diagram": { "revision": 1, "id": "g6pd-red-cell-redox-map", "title": "Follow reducing power through a red blood cell", "subtitle": "A gene, an enzyme, a pathway, and a redox cycle meet in one cell-specific mechanism.", "note": "This is a selected mechanism, not a complete red-cell redox network. The oxidative pentose-phosphate branch makes NADPH through both G6PD and 6-phosphogluconate dehydrogenase. G6PD variants differ, and an oxidative challenge does not cause hemolysis in every person or every exposure.", "sources": [ { "label": "Reactome · Human pentose phosphate pathway R-HSA-71336", "href": "https://reactome.org/content/detail/R-HSA-71336" }, { "label": "NCBI Bookshelf · Tafenoquine Therapy and G6PD Genotype", "href": "https://www.ncbi.nlm.nih.gov/books/NBK562890/" }, { "label": "CPIC · G6PD genotype and medication risk guideline", "href": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10281211/" } ], "lanes": [ { "label": "Gene to pathway", "note": "The gene encodes an enzyme; the enzyme catalyzes a pathway reaction.", "links": [ "encodes", "catalyzes the first oxidative step of" ], "assertionIds": [ "g6pd.gene-encodes-enzyme", "g6pd.enzyme-first-oxidative-step" ], "nodes": [ { "label": "G6PD gene", "detail": "A protein-coding human gene with multiple transcript and protein isoforms.", "href": "/gene/g6pd" }, { "label": "G6PD enzyme", "detail": "Oxidizes glucose 6-phosphate and reduces NADP+ in the pathway's first oxidative reaction.", "href": "/protein/g6pd" }, { "label": "Pentose phosphate pathway", "detail": "Its oxidative branch generates NADPH in two dehydrogenase reactions.", "href": "/pathway/pentose-phosphate", "location": "Cytosol" } ] }, { "label": "Recycle the antioxidant pool", "note": "NADPH supplies reducing power; it does not destroy peroxides by itself.", "links": [ "glutathione reductase uses NADPH to regenerate" ], "assertionIds": [ "g6pd.nadph-recycles-glutathione" ], "nodes": [ { "label": "NADPH + GSSG", "detail": "NADPH supplies electrons while oxidized glutathione is reduced.", "href": "/molecule/nadph" }, { "label": "Reduced glutathione (GSH)", "detail": "GSH is used by glutathione peroxidases in peroxide-reduction reactions.", "href": "/molecule/glutathione-reduced" } ] }, { "label": "Reduce peroxide", "note": "GPX1 is one part of a broader antioxidant network.", "links": [ "GPX1 can use GSH to reduce" ], "assertionIds": [ "g6pd.glutathione-reduces-peroxide" ], "nodes": [ { "label": "Reduced glutathione (GSH)", "detail": "The reducing substrate used by glutathione peroxidases.", "href": "/molecule/glutathione-reduced" }, { "label": "Hydrogen peroxide", "detail": "GPX1 can reduce it to water while GSH is oxidized to GSSG; peroxide can also participate in signaling.", "href": "/molecule/hydrogen-peroxide" } ] }, { "label": "Cell-specific disease mechanism", "note": "The pathway changes susceptibility; it is not a deterministic forecast for a person.", "links": [ "can limit NADPH response in" ], "assertionIds": [ "g6pd.deficiency-can-limit-redox-response" ], "nodes": [ { "label": "G6PD deficiency", "detail": "Variants leave different residual enzyme activities and clinical phenotypes.", "href": "/disease/g6pd-deficiency" }, { "label": "Mature red blood cell", "detail": "Some variants can leave erythrocytes less able to replenish NADPH during an oxidative challenge.", "href": "/cell_type/erythrocyte" } ] }, { "label": "Clinical outcome and exposure", "note": "Infection, medicines, and other oxidant exposures differ; this is not a personal medication-risk tool.", "links": [ "may be associated with acute hemolysis in susceptible contexts" ], "assertionIds": [ "g6pd.oxidative-exposures-and-hemolysis" ], "nodes": [ { "label": "G6PD deficiency", "detail": "Risk varies with variant, residual activity, cell age, the exposure, and clinical context.", "href": "/disease/g6pd-deficiency" }, { "label": "Possible acute hemolysis", "detail": "An outcome that can occur after particular infections or oxidant exposures; it is not inevitable.", "href": "/disease/g6pd-deficiency" } ] } ] }, "connectedRecords": [ { "id": "gene-g6pd", "type": "gene", "slug": "g6pd", "name": "G6PD", "canonicalName": "glucose-6-phosphate dehydrogenase", "summary": "Encodes the enzyme that catalyzes the first oxidative step of the pentose phosphate pathway." }, { "id": "protein-g6pd", "type": "protein", "slug": "g6pd", "name": "Glucose-6-phosphate Dehydrogenase", "canonicalName": "G6PD · EC 1.1.1.49", "summary": "G6PD catalyzes the first reaction of the oxidative pentose phosphate pathway, reducing NADP+ to NADPH." }, { "id": "pathway-pentose-phosphate", "type": "pathway", "slug": "pentose-phosphate", "name": "Pentose Phosphate pathway", "canonicalName": "Pentose phosphate pathway in human metabolism", "summary": "The pentose phosphate pathway branches from glucose 6-phosphate. Its oxidative branch makes NADPH and ribulose 5-phosphate; its reversible non-oxidative reactions interconvert pentoses with glycolytic intermediates to match biosynthetic demand." }, { "id": "molecule-nadph", "type": "molecule", "slug": "nadph", "name": "NADPH", "canonicalName": "NADPH", "summary": "Reduced nicotinamide adenine dinucleotide phosphate; it supplies reducing power for biosynthesis and antioxidant defense." }, { "id": "protein-glutathione-reductase", "type": "protein", "slug": "glutathione-reductase", "name": "Glutathione Reductase", "canonicalName": "Glutathione-disulfide reductase · GSR", "summary": "Glutathione reductase uses NADPH to convert oxidized glutathione (GSSG) back to reduced glutathione (GSH)." }, { "id": "molecule-glutathione-disulfide", "type": "molecule", "slug": "glutathione-disulfide", "name": "Oxidized Glutathione (GSSG)", "canonicalName": "glutathione disulfide", "summary": "GSSG is the oxidized form produced when glutathione participates in some peroxide-reduction reactions." }, { "id": "molecule-glutathione-reduced", "type": "molecule", "slug": "glutathione-reduced", "name": "Reduced Glutathione (GSH)", "canonicalName": "γ-glutamyl-cysteinyl-glycine, reduced form", "summary": "GSH is a small antioxidant molecule used by enzymes such as GPX1 to reduce peroxides." }, { "id": "protein-gpx1", "type": "protein", "slug": "gpx1", "name": "Glutathione Peroxidase 1", "canonicalName": "GPX1 · cytosolic glutathione peroxidase", "summary": "GPX1 uses reduced glutathione to reduce hydrogen peroxide and other peroxides." }, { "id": "molecule-hydrogen-peroxide", "type": "molecule", "slug": "hydrogen-peroxide", "name": "Hydrogen Peroxide (H₂O₂)", "canonicalName": "hydrogen peroxide", "summary": "Hydrogen peroxide is a reactive oxygen species that can act in signaling but can also contribute to oxidative damage when not controlled." }, { "id": "cell-type-erythrocyte", "type": "cell_type", "slug": "erythrocyte", "name": "Erythrocyte", "canonicalName": "Erythrocyte", "summary": "An erythrocyte, or red blood cell, carries oxygen through the blood using hemoglobin." }, { "id": "process-oxidative-stress", "type": "process", "slug": "oxidative-stress", "name": "Oxidative Stress", "canonicalName": "imbalance between oxidant challenge and cellular defenses", "summary": "Oxidative stress describes a redox disturbance in which oxidant production or exposure exceeds the capacity of protective systems." }, { "id": "disease-g6pd-deficiency", "type": "disease", "slug": "g6pd-deficiency", "name": "G6PD Deficiency", "canonicalName": "Glucose-6-phosphate dehydrogenase deficiency", "summary": "Variants that reduce G6PD activity can leave red blood cells less able to manage oxidative stress." } ], "references": [ { "id": "reactome-pentose-phosphate", "title": "Pentose phosphate pathway (R-HSA-71336)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-71336", "kind": "pathway" }, { "id": "ncbi-g6pd", "title": "G6PD glucose-6-phosphate dehydrogenase (Gene ID 2539)", "publisher": "NCBI Gene", "url": "https://www.ncbi.nlm.nih.gov/gene/2539", "kind": "database" }, { "id": "uniprot-g6pd", "title": "Glucose-6-phosphate 1-dehydrogenase (P11413)", "publisher": "UniProtKB", "url": "https://www.uniprot.org/uniprotkb/P11413/entry", "kind": "database" }, { "id": "ncbi-g6pd-mgs", "title": "Tafenoquine Therapy and G6PD Genotype (NBK562890)", "publisher": "Medical Genetics Summaries · NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK562890/", "kind": "review" }, { "id": "g6pd-redox-review", "title": "Impact of G6PD status on red cell storage and transfusion outcomes", "publisher": "Transfusion Medicine Reviews · PMC6683872", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6683872/", "kind": "review" }, { "id": "g6pd-cpic-2023", "title": "Expanded CPIC Guideline for Medication Use in the Context of G6PD Genotype", "publisher": "Clinical Pharmacology & Therapeutics · PMC10281211", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10281211/", "kind": "guide" }, { "id": "ncbi-gsr", "title": "GSR glutathione-disulfide reductase (Gene ID 2936)", "publisher": "NCBI Gene", "url": "https://www.ncbi.nlm.nih.gov/gene/2936", "kind": "database" }, { "id": "ncbi-gpx1", "title": "GPX1 glutathione peroxidase 1 (Gene ID 2876)", "publisher": "NCBI Gene", "url": "https://www.ncbi.nlm.nih.gov/gene/2876", "kind": "database" }, { "id": "uniprot-gpx1", "title": "Glutathione peroxidase 1 (P07203)", "publisher": "UniProtKB", "url": "https://www.uniprot.org/uniprotkb/P07203/entry", "kind": "database" } ], "mechanismEvidence": { "schemaVersion": "BASE-biological-assertion/1.1.0", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "groups": [ { "id": "gene-pathway", "title": "Gene & Pathway", "description": "How G6PD connects to the pathway’s NADPH output.", "assertionIds": [ "g6pd.gene-encodes-enzyme", "g6pd.enzyme-first-oxidative-step", "g6pd.catalyzes-ppp-entry-reaction", "g6pd.oxidative-branch-produces-nadph" ] }, { "id": "red-cell-context", "title": "Red-Cell Context", "description": "Why this pathway matters in mature erythrocytes.", "assertionIds": [ "g6pd.erythrocyte-nadph-context" ] }, { "id": "antioxidant-defense", "title": "Antioxidant Defense", "description": "How NADPH and glutathione support peroxide removal.", "assertionIds": [ "g6pd.nadph-recycles-glutathione", "g6pd.glutathione-reduces-peroxide" ] }, { "id": "disease-context", "title": "Disease & Exposure Context", "description": "What the mechanism can explain—and what it cannot predict.", "assertionIds": [ "g6pd.deficiency-can-limit-redox-response", "g6pd.oxidative-exposures-and-hemolysis" ] } ], "assertions": [ { "id": "g6pd.gene-encodes-enzyme", "version": 1, "subjectId": "gene-g6pd", "predicate": "ENCODES", "objectId": "protein-g6pd", "statement": "The human G6PD gene encodes glucose-6-phosphate dehydrogenase.", "qualifier": "NCBI annotates G6PD as a protein-coding gene and lists multiple transcript/protein isoforms.", "evidenceKind": "database_annotation", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd", "relation": "supports", "sourceRecordId": "NCBI Gene:2539", "sourceVersion": "Record updated 2026-09-13" }, { "referenceId": "uniprot-g6pd", "relation": "supports", "sourceRecordId": "UniProt:P11413", "sourceVersion": "Reviewed entry; release not recorded in this snapshot" } ] }, { "id": "g6pd.enzyme-first-oxidative-step", "version": 1, "subjectId": "protein-g6pd", "predicate": "CATALYZES_STEP_IN", "objectId": "pathway-pentose-phosphate", "statement": "G6PD catalyzes the first oxidative reaction of the pentose phosphate pathway, reducing NADP+ as glucose 6-phosphate is oxidized.", "qualifier": "This is the pathway entry reaction; 6-phosphogluconate dehydrogenase also generates NADPH later in the oxidative branch.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "ncbi-g6pd", "relation": "supports", "sourceRecordId": "NCBI Gene:2539", "sourceVersion": "Record updated 2026-09-13" } ] }, { "id": "g6pd.catalyzes-ppp-entry-reaction", "version": 1, "subjectId": "protein-g6pd", "predicate": "CATALYZES_REACTION", "objectValue": { "kind": "reaction", "pathwaySlug": "pentose-phosphate", "reactionSlug": "pentose-phosphate-01", "stepNumber": 1, "name": "Oxidation of glucose 6-phosphate" }, "statement": "G6PD catalyzes the pentose-phosphate pathway's entry reaction, oxidizing glucose 6-phosphate while reducing NADP+ to NADPH.", "qualifier": "This is a selected human teaching reaction from the oxidative branch. It is not a complete representation of pathway flux or every cellular context.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336; local reaction pentose-phosphate-01", "sourceVersion": "Reactome release not recorded in this snapshot" } ] }, { "id": "g6pd.oxidative-branch-produces-nadph", "version": 1, "subjectId": "pathway-pentose-phosphate", "predicate": "GENERATES_IN_OXIDATIVE_BRANCH", "objectId": "molecule-nadph", "statement": "The oxidative branch of the human pentose phosphate pathway generates NADPH.", "qualifier": "The two oxidative dehydrogenase reactions contribute NADPH; the pathway also supplies pentose-phosphate intermediates, and net flux depends on cellular demand.", "evidenceKind": "curated_pathway", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "reactome-pentose-phosphate", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71336", "sourceVersion": "Stable identifier; release not recorded in this snapshot" } ] }, { "id": "g6pd.erythrocyte-nadph-context", "version": 1, "subjectId": "cell-type-erythrocyte", "predicate": "DEPENDS_ON_FOR_NADPH", "objectId": "pathway-pentose-phosphate", "statement": "Mature human red blood cells lack mitochondria and rely on the pentose phosphate pathway for NADPH production.", "qualifier": "This statement is scoped to mature erythrocytes; it should not be generalized to nucleated cells or other tissues.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd-mgs", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.nadph-recycles-glutathione", "version": 1, "subjectId": "molecule-nadph", "predicate": "SUPPORTS_REGENERATION_OF", "objectId": "molecule-glutathione-reduced", "statement": "NADPH powers glutathione reductase to convert oxidized glutathione (GSSG) back to reduced glutathione (GSH).", "qualifier": "GSH is one part of red-cell antioxidant defense; this simplified chain does not represent every peroxide-removal or redox system.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-gsr", "relation": "supports", "sourceRecordId": "NCBI Gene:2936", "sourceVersion": "Record accessed 2026-09-27" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.glutathione-reduces-peroxide", "version": 1, "subjectId": "molecule-glutathione-reduced", "predicate": "SUPPORTS_PEROXIDE_REDUCTION", "objectId": "molecule-hydrogen-peroxide", "statement": "GPX1 can use GSH to reduce hydrogen peroxide to water, producing GSSG.", "qualifier": "GPX1 is one contributor; other antioxidant enzymes and context-specific redox processes also matter.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-gpx1", "relation": "supports", "sourceRecordId": "NCBI Gene:2876", "sourceVersion": "Record updated 2026-09-13" }, { "referenceId": "uniprot-gpx1", "relation": "supports", "sourceRecordId": "UniProt:P07203", "sourceVersion": "Entry release not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" } ] }, { "id": "g6pd.deficiency-can-limit-redox-response", "version": 1, "subjectId": "disease-g6pd-deficiency", "predicate": "CAN_LIMIT_NADPH_RESPONSE", "objectId": "cell-type-erythrocyte", "statement": "Some G6PD variants reduce enzyme activity and can leave erythrocytes less able to replenish NADPH during an oxidative challenge.", "qualifier": "Residual activity, variant, erythrocyte age, sex and X-chromosome inactivation, exposure, and other biology affect phenotype; this is not a deterministic individual prediction.", "evidenceKind": "mechanistic_review", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "ncbi-g6pd-mgs", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" }, { "referenceId": "g6pd-redox-review", "relation": "supports", "sourceRecordId": "PMCID:PMC6683872", "sourceVersion": "Published 2019" }, { "referenceId": "g6pd-cpic-2023", "relation": "qualifies", "sourceRecordId": "CPIC guideline; PMCID:PMC10281211", "sourceVersion": "Published 2023" } ] }, { "id": "g6pd.oxidative-exposures-and-hemolysis", "version": 1, "subjectId": "disease-g6pd-deficiency", "predicate": "MAY_BE_ASSOCIATED_WITH", "objectValue": "Acute hemolysis in susceptible contexts", "statement": "Some people with G6PD deficiency can develop acute hemolysis after particular infections or oxidant exposures, including some medications.", "qualifier": "Risk differs by drug, dose, genotype, residual enzyme activity, co-exposures, and clinical state. BASE does not classify a user's medication as safe or unsafe or predict personal risk.", "evidenceKind": "clinical_guideline", "context": { "scope": "Homo sapiens · mature erythrocyte · G6PD deficiency under oxidative challenge", "organism": "Homo sapiens", "taxonId": "9606", "cellTypeId": "cell-type-erythrocyte", "cellStage": "Mature erythrocyte", "conditionId": "disease-g6pd-deficiency", "exposureContext": "Oxidative challenge; triggers and response vary by genotype and individual context." }, "references": [ { "referenceId": "g6pd-cpic-2023", "relation": "supports", "sourceRecordId": "CPIC guideline; PMCID:PMC10281211", "sourceVersion": "Published 2023" }, { "referenceId": "ncbi-g6pd-mgs", "relation": "qualifies", "sourceRecordId": "NCBI Bookshelf:NBK562890", "sourceVersion": "Page version not recorded in this snapshot" } ] } ], "limitation": "Educational mechanism map only. It does not diagnose G6PD deficiency or predict an individual's clinical or medication risk." } } }