{"id":"14f4974f-071f-5356-ba10-38ea8dd443f9","stable_key":"availability:uneven-selenoprotein-response:1","predicate":"can_reduce_expression_of","statement":"Selenium restriction often strongly reduces GPX1 expression or activity in experimental models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"source_reported: Animal model and cell/biochemical; source-derived unverified synthesis.","direction":"negative","is_public":true,"mechanism_event_id":"f3887c44-e01f-55cd-8a5f-5d889da03922","mechanism_event_label":"Selenium restriction often strongly reduces GPX1 expression or activity in experimental models.","subject":{"id":"dc89d7e2-8f89-577b-838f-42bf5d8ec7c8","slug":"selenium","display_name":"Selenium","entity_type_key":"nutrient_element"},"object":{"id":"e79d035c-0c02-5c0e-ac8f-d7fdeb663fbd","slug":"gpx1","display_name":"GPX1","entity_type_key":"protein"},"evidence_count":2,"mechanism_event":{"id":"f3887c44-e01f-55cd-8a5f-5d889da03922","stable_key":"availability:uneven-selenoprotein-response:1","event_type":"availability_dependent_change","label":"Selenium restriction often strongly reduces GPX1 expression or activity in experimental models.","description":"Selenium supply is restricted for a defined tissue, species, and duration. Predominantly animal and cell models; ranking varies with tissue, species, development, duration, and measurement.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc89d7e2-8f89-577b-838f-42bf5d8ec7c8","slug":"selenium","display_name":"Selenium","entity_type_key":"nutrient_element"},"role":"condition_input","stoichiometry":null,"state_label":"Selenium supply is restricted for a defined tissue, species, and duration.","sequence_order":0,"notes":""},{"entity":{"id":"e79d035c-0c02-5c0e-ac8f-d7fdeb663fbd","slug":"gpx1","display_name":"GPX1","entity_type_key":"protein"},"role":"affected_component","stoichiometry":null,"state_label":"Selenium supply is restricted for a defined tissue, species, and duration.","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"Selenium supply is restricted for a defined tissue, species, and duration.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_scope","value_text":"Predominantly animal and cell models; ranking varies with tissue, species, development, duration, and measurement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Relative preservation does not mean immunity to severe loss. Um34 alone does not implement a universal ranking, and no plasma-to-protein cutoff is assigned.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"167d2f66-d612-5a54-93bc-37b0c8c3efb5","evidence_kind":"source_passage","locator":"lines 101-117","start_line":101,"end_line":117,"excerpt":"2.1 Protein hierarchy: useful, but schematic\n\nDifferent selenoproteins respond differently to selenium restriction. A useful conceptual grouping is:\n\nMore selenium-responsive in many models\n\nIntermediate / context-dependent\n\nRelatively preserved in severe restriction\n\nGPX1, SELENOW\n\nGPX3, SELENOP, DIO1, SELENOK, SELENOM\n\nGPX4, TXNRD1, DIO2, SEPHS2\n\nThis is a schematic hierarchy, not a literal universal sequence of death. Ordering varies with tissue, species, developmental stage, duration of deficiency, and how the endpoint is measured.","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}},{"id":"5e14c14f-8e04-5d6e-9519-4b60cd5a8e4e","evidence_kind":"source_passage","locator":"lines 287-293","start_line":287,"end_line":293,"excerpt":"GPX1 activity ↓\n\nOften strongly selenium-responsive\n\nGPX1 mRNA ↓ in susceptible models\n\nNMD can contribute","model_system":"Supplied reference; verify the primary study and experimental context.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c788c19c-884c-5233-92b1-0bd063d87741","stable_key":"deficiency","title":"Selenium deficiency: a mechanism-first reference","document_type":"user_supplied_reference","citation_label":"Supplied selenium deficiency reference","file_path":"X:\\metabolic-ledger\\source_material\\selenium-deficiency-reference.md","sha256":"a3f14bc3fa24c595dda830664523090a7b5bfa76e9dcf517f42f62212ceb767e","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","review_status":"unverified_draft","notes":"Preserved verbatim. Reported study types are source labels, not independent verification."}}],"relations":[],"conflicts":[],"corrections":[],"research":null}