{"id":"c8fe4659-4c1e-5f64-9168-f77db1db23f5","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-hfe-association","predicate":"variants_associated_with","statement":"A major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7519cfb0-0a67-533a-b333-c63a455dc031","mechanism_event_label":"The body’s iron-control machinery can be defective even when dietary supply is ordinary.","subject":{"id":"2eb1f308-9ded-5502-b553-0cd30393f22c","slug":"hfe","display_name":"Human homeostatic iron regulator / HFE","entity_type_key":"protein"},"object":{"id":"618f7d71-8187-5bca-9680-9c313fe537b4","slug":"systemic-iron-overload","display_name":"Systemic tissue iron overload","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7519cfb0-0a67-533a-b333-c63a455dc031","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-hfe-association-event","event_type":"observed_intervention","label":"The body’s iron-control machinery can be defective even when dietary supply is ordinary.","description":"A major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2eb1f308-9ded-5502-b553-0cd30393f22c","slug":"hfe","display_name":"Human homeostatic iron regulator / HFE","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"618f7d71-8187-5bca-9680-9c313fe537b4","slug":"systemic-iron-overload","display_name":"Systemic tissue iron overload","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iron-research/8696333.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a\", \"start_char\": 0, \"end_char\": 921, \"text_sha256\": \"812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Linkage disequilibrium and human genetic association","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"HFE discovery and missense variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Historical selected population; 83% is not penetrance or a current general-population risk estimate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"178 hereditary-hemochromatosis patients in the reported cohort","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The body’s iron-control machinery can be defective even when dietary supply is ordinary.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p8696333] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. (1996). https://pubmed.ncbi.nlm.nih.gov/8696333/ DOI: 10.1038/ng0896-399","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Genetic iron-overload phenotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"3802a0dc-948e-56ac-96f4-71a51ce0f02f","evidence_kind":"source_excerpt","locator":"Lines 1213-1224","start_line":1213,"end_line":1224,"excerpt":"### iron-hfe-association\nA major HFE missense alteration was homozygous in 83% of 178 hereditary-hemochromatosis patients in the discovery cohort.\nCondition category: machinery_impairment\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The body’s iron-control machinery can be defective even when dietary supply is ordinary.\norganism: 178 hereditary-hemochromatosis patients in the reported cohort\ntissue_or_cell_type: Genetic iron-overload phenotype\nexperimental_model: Linkage disequilibrium and human genetic association\nlimitations: Historical selected population; 83% is not penetrance or a current general-population risk estimate.\nexposure: HFE discovery and missense variants\nevidence_span: {\"source_cache\": \"artifacts/iron-research/8696333.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a\", \"start_char\": 0, \"end_char\": 921, \"text_sha256\": \"812dfc62980bb4a17920e9eb490a2d1abc529b468c0531ffd59011713a60a15a\"}\n[iron-p8696333] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. (1996). https://pubmed.ncbi.nlm.nih.gov/8696333/ DOI: 10.1038/ng0896-399","model_system":"Linkage disequilibrium and human genetic association","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iron-p8696333] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. (1996). https://pubmed.ncbi.nlm.nih.gov/8696333/ DOI: 10.1038/ng0896-399","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1560864c-91d1-58dc-90c4-49bf61aba3de","stable_key":"import-e13b03e1-a614-543a-ac1b-97df18cfe30d","title":"Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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