{"id":"2a01a82e-1591-5bc9-a524-e088d340b611","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-aml-redundancy","predicate":"functionally_complements","statement":"Gain- and loss-of-function experiments supported redundant contributions of ISYNA1 synthesis and SLC5A3 transport to intracellular inositol and AML-cell fitness.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b7bd1138-0e0f-52d2-a338-c2013ae9e3e3","mechanism_event_label":"Restoring synthesis can remove dependence on the same import route.","subject":{"id":"bab0b109-e18f-5fe1-8631-364242ec78f4","slug":"isyna1","display_name":"ISYNA1 (human inositol-3-phosphate synthase 1)","entity_type_key":"protein"},"object":{"id":"5453efb2-0a63-560e-9a73-69113a43bd5b","slug":"slc5a3","display_name":"SLC5A3 (human SMIT1)","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"b7bd1138-0e0f-52d2-a338-c2013ae9e3e3","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-aml-redundancy-event","event_type":"biochemical_relationship","label":"Restoring synthesis can remove dependence on the same import route.","description":"Gain- and loss-of-function experiments supported redundant contributions of ISYNA1 synthesis and SLC5A3 transport to intracellular inositol and AML-cell fitness.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"292eaea9-bfaf-5e6e-bc22-3048da3182e1","slug":"intracellular-myo-inositol","display_name":"Intracellular myo-inositol availability","entity_type_key":"cellular_process"},"role":"maintained_pool","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"aef46849-0734-59b9-9f3d-c9ba24a5a3c8","slug":"aml-cell-survival","display_name":"Acute myeloid leukemia cell survival","entity_type_key":"cellular_process"},"role":"outcome","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bab0b109-e18f-5fe1-8631-364242ec78f4","slug":"isyna1","display_name":"ISYNA1 (human inositol-3-phosphate synthase 1)","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5453efb2-0a63-560e-9a73-69113a43bd5b","slug":"slc5a3","display_name":"SLC5A3 (human SMIT1)","entity_type_key":"protein"},"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":"evidence_span","value_text":"{\"source_cache\": \"artifacts/inositol-research/34531253.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\", \"start_char\": 0, \"end_char\": 1431, \"text_sha256\": \"e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Genetic screening, gain/loss of function and patient sample profiling","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLC5A3/ISYNA1 perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Inositol research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"inositol","display_name":"Inositol (stereoisomer family)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human AML cells and in vivo leukemia models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Restoring synthesis can remove dependence on the same import route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. 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