{"id":"3075e4d8-b87d-5858-8260-9807fbde5bcf","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-duoxa-mutant-function","predicate":"fails_to_support","statement":"Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"eb17e392-b92a-57a7-9c5a-5388c3e71b48","mechanism_event_label":"This truncated helper protein could not support peroxide production.","subject":{"id":"cb22115a-d7cb-584e-a726-603da4fd015a","slug":"human-duoxa2-y246x","display_name":"Human DUOXA2 p.Y246X truncation","entity_type_key":"protein_state"},"object":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"eb17e392-b92a-57a7-9c5a-5388c3e71b48","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-duoxa-mutant-function-event","event_type":"biochemical_relationship","label":"This truncated helper protein could not support peroxide production.","description":"Human DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d40c8af1-fd0c-5865-8790-af43e38a5d84","slug":"duoxa2","display_name":"Human dual oxidase maturation factor 2","entity_type_key":"protein"},"role":"wild_type_control","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"20429538-a23e-5e16-b4ad-4bcb42727e71","slug":"duox2","display_name":"Human dual oxidase 2","entity_type_key":"protein"},"role":"dependent_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"cb22115a-d7cb-584e-a726-603da4fd015a","slug":"human-duoxa2-y246x","display_name":"Human DUOXA2 p.Y246X truncation","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iodine-synthesis-sources/18042646.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7\", \"text_characters\": 1847, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human genetic case finding and heterologous DUOX2 reconstitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Y246X mutant versus wild-type DUOXA2 in reconstitution.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Loss of enzyme machinery, not iodine or riboflavin shortage.","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 proteins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This truncated helper protein could not support peroxide production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Heterologous cells","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":"3fbbfcb6-aa0a-59e8-9c34-9f8c07b91d6b","evidence_kind":"source_excerpt","locator":"Lines 534-546","start_line":534,"end_line":546,"excerpt":"### iodine-syn-duoxa-mutant-function\nHuman DUOXA2 p.Y246X failed to reconstitute DUOX2 activity in vitro.\nCondition category: machinery_impairment\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This truncated helper protein could not support peroxide production.\norganism: Homo sapiens proteins\ntissue_or_cell_type: Heterologous cells\nexperimental_model: Human genetic case finding and heterologous DUOX2 reconstitution\nlimitations: Loss of enzyme machinery, not iodine or riboflavin shortage.\nexposure: Y246X mutant versus wild-type DUOXA2 in reconstitution.\ncross_nutrient: false\nevidence_span: {\"source_cache\": \"artifacts/iodine-synthesis-sources/18042646.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"99a0667a0a4036b9ad94f59e6ba82a4c80c7f4b4228f11029f63db5c5b811da7\", \"text_characters\": 1847, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}\n[iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020","model_system":"Human genetic case finding and heterologous DUOX2 reconstitution","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iodine-syn-duoxa2008] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18042646/ DOI: 10.1210/jc.2007-2020","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess 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. Not publisher full text.","file_path":"","sha256":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}