{"id":"d831175a-3bac-5371-841a-b1bad8ce7a7a","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-tmprss6-irida","predicate":"pathogenic_variants_cause","statement":"Germline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"586c485d-2d2c-51db-b8a9-b42426a95f4d","mechanism_event_label":"The problem can be the body’s control of iron availability, rather than simply too little iron supplied.","subject":{"id":"7688b573-5f22-5fe5-9814-ddd599d956ee","slug":"tmprss6","display_name":"Human matriptase-2 / TMPRSS6","entity_type_key":"protein"},"object":{"id":"4f52d953-3959-53d5-b161-316aa9512292","slug":"refractory-microcytic-anemia","display_name":"Microcytic anemia refractory to oral iron in genetic iron-handling disorders","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"586c485d-2d2c-51db-b8a9-b42426a95f4d","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-tmprss6-irida-event","event_type":"biochemical_relationship","label":"The problem can be the body’s control of iron availability, rather than simply too little iron supplied.","description":"Germline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6d4be6b8-eba9-5d6b-93f9-4642b87f7b6f","slug":"hamp","display_name":"Hepcidin","entity_type_key":"protein"},"role":"regulated_hormone","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7688b573-5f22-5fe5-9814-ddd599d956ee","slug":"tmprss6","display_name":"Human matriptase-2 / TMPRSS6","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4f52d953-3959-53d5-b161-316aa9512292","slug":"refractory-microcytic-anemia","display_name":"Microcytic anemia refractory to oral iron in genetic iron-handling disorders","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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/18408718.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e\", \"start_char\": 0, \"end_char\": 468, \"text_sha256\": \"26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Family genetic investigation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Germline TMPRSS6 variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rare inherited disorder; not an explanation for every failure of oral iron.","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":"Humans with refractory iron-deficiency anemia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The problem can be the body’s control of iron availability, rather than simply too little iron supplied.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p18408718] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). (2008). https://pubmed.ncbi.nlm.nih.gov/18408718/ DOI: 10.1038/ng.130","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Systemic iron regulation","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":"3d91d7bb-2521-5f5d-84ca-7e3e55bdccb2","evidence_kind":"source_excerpt","locator":"Lines 1018-1029","start_line":1018,"end_line":1029,"excerpt":"### iron-tmprss6-irida\nGermline TMPRSS6 mutations caused iron-deficiency anemia refractory to oral iron therapy in the studied families.\nCondition category: machinery_impairment\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The problem can be the body’s control of iron availability, rather than simply too little iron supplied.\norganism: Humans with refractory iron-deficiency anemia\ntissue_or_cell_type: Systemic iron regulation\nexperimental_model: Family genetic investigation\nlimitations: Rare inherited disorder; not an explanation for every failure of oral iron.\nexposure: Germline TMPRSS6 variants\nevidence_span: {\"source_cache\": \"artifacts/iron-research/18408718.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e\", \"start_char\": 0, \"end_char\": 468, \"text_sha256\": \"26d5ec56d21c4675127615cc14ef1b167eef0d8c5e2fe7d69a5b316f4e06011e\"}\n[iron-p18408718] Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). 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