{"id":"d5aec06a-28ef-5b31-bcc9-c3e17b69f513","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-duoxa-mutant-phenotype","predicate":"associated_with","statement":"The homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"391ed3aa-ef09-5ea3-9f16-51473b78b061","mechanism_event_label":"The enzyme-helper defect was linked to impaired hormone production from birth.","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":"5b33cb30-4cc6-5e0a-b6ed-0528939e1730","slug":"dyshormonogenic-hypothyroidism","display_name":"Dyshormonogenic hypothyroidism","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"391ed3aa-ef09-5ea3-9f16-51473b78b061","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-duoxa-mutant-phenotype-event","event_type":"observed_intervention","label":"The enzyme-helper defect was linked to impaired hormone production from birth.","description":"The homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment.","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":"affected_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"83b11ca6-52c7-5a1b-8c39-d9cdf89244e3","slug":"iodide","display_name":"Iodide ion","entity_type_key":"ion"},"role":"organification_substrate","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":"5b33cb30-4cc6-5e0a-b6ed-0528939e1730","slug":"dyshormonogenic-hypothyroidism","display_name":"Dyshormonogenic hypothyroidism","entity_type_key":"cellular_process"},"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":"Inherited homozygous Y246X; no dietary manipulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Single proband; heterozygotes in the family were euthyroid.","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":"The enzyme-helper defect was linked to impaired hormone production from birth.","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":"Thyroid","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":"aaac3eeb-9dd6-541d-a972-2282d9ee41cc","evidence_kind":"source_excerpt","locator":"Lines 548-560","start_line":548,"end_line":560,"excerpt":"### iodine-syn-duoxa-mutant-phenotype\nThe homozygous DUOXA2 Y246X proband had congenital hypothyroidism with goiter and partial iodine-organification impairment.\nCondition category: machinery_impairment\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The enzyme-helper defect was linked to impaired hormone production from birth.\norganism: Homo sapiens\ntissue_or_cell_type: Thyroid\nexperimental_model: Human genetic case finding and heterologous DUOX2 reconstitution\nlimitations: Single proband; heterozygotes in the family were euthyroid.\nexposure: Inherited homozygous Y246X; no dietary manipulation.\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. 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