{"id":"f2de4ce2-3a1b-510d-b769-1e3fdc43bb6e","stable_key":"3ad23a58-d6a8-5554-81d6-9c83abd33087:znt8-cytosolic-zinc","predicate":"reported_comparison","statement":"SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ef833026-95c8-586f-85bd-078211781dfd","mechanism_event_label":"SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.","subject":{"id":"5ec5ce4e-ee24-5bff-a525-5e57fc4db7c3","slug":"human-slc30a8-null-beta-cells","display_name":"Human stem-cell-derived SLC30A8-null beta cells","entity_type_key":"cell_type"},"object":{"id":"6b6f8c08-d851-5e91-8087-c6929c98a1a1","slug":"human-beta-cell-cytosolic-zinc","display_name":"Human beta-cell cytosolic free zinc pool","entity_type_key":"ion"},"evidence_count":1,"mechanism_event":{"id":"ef833026-95c8-586f-85bd-078211781dfd","stable_key":"3ad23a58-d6a8-5554-81d6-9c83abd33087:znt8-cytosolic-zinc","event_type":"reported_comparison","label":"SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.","description":"","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5ec5ce4e-ee24-5bff-a525-5e57fc4db7c3","slug":"human-slc30a8-null-beta-cells","display_name":"Human stem-cell-derived SLC30A8-null beta cells","entity_type_key":"cell_type"},"role":"experimental_actor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6b6f8c08-d851-5e91-8087-c6929c98a1a1","slug":"human-beta-cell-cytosolic-zinc","display_name":"Human beta-cell cytosolic free zinc pool","entity_type_key":"ion"},"role":"measured_endpoint","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a4da847b-7430-527e-bc73-8d17fd5255ba","slug":"slc30a8","display_name":"Human zinc transporter ZnT8 / SLC30A8","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0429f0ff-c033-514b-9a4f-6f0f83268095","slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"},"role":"context_participant","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":"curation_topic","value_text":"zinc","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"experimental_condition","value_text":"SLC30A8 knockout","comparator":"Wild-type cells","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"human-slc30a8-null-beta-cells","display_name":"Human stem-cell-derived SLC30A8-null beta cells","entity_type_key":"cell_type"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"SLC30A8 knockout\", \"comparator\": \"Wild-type cells\", \"endpoint\": \"Cytosolic free zinc\", \"effect_direction\": \"increase\", \"combination\": \"single\", \"conditions\": [{\"entity_slug\": \"human-slc30a8-null-beta-cells\", \"state\": \"SLC30A8 knockout\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Compartment-specific sensor measurement; not total-body zinc.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/","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":"1b1731db-e776-5140-a892-cf6e3164b215","evidence_kind":"source_excerpt","locator":"Lines 9-9","start_line":9,"end_line":9,"excerpt":"SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation. Model: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed. Limits: Compartment-specific sensor measurement; not total-body zinc. 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