{"id":"69454ea4-777b-5a51-90ef-503f1a483712","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-secisbp2-fibroblast-dio2","predicate":"reduces","statement":"Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"1611aeaa-e7a2-5c09-a415-23ce60febcc8","mechanism_event_label":"A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.","subject":{"id":"f8668af8-9e22-5100-9575-c9f8e156acbb","slug":"secisbp2-recessive-defect-patients","display_name":"Patients with recessive SECISBP2 defects","entity_type_key":"organism"},"object":{"id":"fc93f0af-2123-58b6-bb7a-ff800479799a","slug":"dio2","display_name":"DIO2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1611aeaa-e7a2-5c09-a415-23ce60febcc8","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:i-met-secisbp2-fibroblast-dio2-event","event_type":"biochemical_relationship","label":"A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.","description":"Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f8668af8-9e22-5100-9575-c9f8e156acbb","slug":"secisbp2-recessive-defect-patients","display_name":"Patients with recessive SECISBP2 defects","entity_type_key":"organism"},"role":"genetic_model","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3a7052da-9a94-5590-af38-341fafc3dbce","slug":"secisbp2","display_name":"SECISBP2 / SBP2","entity_type_key":"protein"},"role":"affected_translation_factor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fc93f0af-2123-58b6-bb7a-ff800479799a","slug":"dio2","display_name":"DIO2","entity_type_key":"protein"},"role":"affected_enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"42620d13-f86a-5e08-acea-7bd24787cbe4","slug":"protein-incorporated-selenocysteine","display_name":"Protein-incorporated selenocysteine residue","entity_type_key":"chemical_species"},"role":"protein_residue_context","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"substrate_context","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/iodine-metabolism-sources/16228000.json\", \"source_field\": \"resultList.result[0].abstractText\", \"start_char\": 0, \"end_char\": 1084}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited SECISBP2 variants; no dietary deprivation exposure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Abstract-only; variant-specific kinetics and dietary rescue were not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient fibroblasts","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":"b1d3bef6-5670-502d-8531-ee34aafac63a","evidence_kind":"source_excerpt","locator":"Lines 1099-1112","start_line":1099,"end_line":1112,"excerpt":"### i-met-secisbp2-fibroblast-dio2\nFibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself.\nCondition category: machinery_impairment\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.\norganism: Homo sapiens\ntissue_or_cell_type: Patient fibroblasts\nexperimental_model: Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis\nlimitations: Abstract-only; variant-specific kinetics and dietary rescue were not established.\nexposure: Inherited SECISBP2 variants; no dietary deprivation exposure.\ncross_nutrient: Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency.\nevidence_locator: Primary abstract\nevidence_spans: [{\"source_document\": \"artifacts/iodine-metabolism-sources/16228000.json\", \"source_field\": \"resultList.result[0].abstractText\", \"start_char\": 0, \"end_char\": 1084}]\n[i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. 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