{"id":"d32693a9-70b7-51ae-b433-982728081c6e","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-impa1-progenitors","predicate":"loss_impairs","statement":"IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b7ad4e28-7f58-5247-903c-fe35803236df","mechanism_event_label":"Failure of the inositol-processing machinery affected developing nerve cells.","subject":{"id":"3f404867-317e-5b5c-92a7-9b6e0411dec3","slug":"impa1","display_name":"IMPA1 (human inositol monophosphatase 1)","entity_type_key":"protein"},"object":{"id":"e6f2b7ed-fbe9-51be-b4b7-f52e408956ac","slug":"neural-progenitor-survival","display_name":"Neural progenitor survival and neurogenesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b7ad4e28-7f58-5247-903c-fe35803236df","stable_key":"e69ef6a0-0e23-5eac-aca1-cf333781b962:ino-impa1-progenitors-event","event_type":"biochemical_relationship","label":"Failure of the inositol-processing machinery affected developing nerve cells.","description":"IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3f404867-317e-5b5c-92a7-9b6e0411dec3","slug":"impa1","display_name":"IMPA1 (human inositol monophosphatase 1)","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e6f2b7ed-fbe9-51be-b4b7-f52e408956ac","slug":"neural-progenitor-survival","display_name":"Neural progenitor survival and neurogenesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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/32839513.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed\", \"start_char\": 0, \"end_char\": 1711, \"text_sha256\": \"5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patient-derived iPSC differentiation and rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biallelic IMPA1 defect and myo-inositol-supplemented medium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Failure of the inositol-processing machinery affected developing nerve cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hippocampal dentate-gyrus-like neuronal progenitors","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":"87c7b6e8-e544-5956-9bf3-c3ed418d92ec","evidence_kind":"source_excerpt","locator":"Lines 1263-1274","start_line":1263,"end_line":1274,"excerpt":"### ino-impa1-progenitors\nIMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation.\nCondition category: machinery_impairment\nnutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Failure of the inositol-processing machinery affected developing nerve cells.\norganism: Homo sapiens\ntissue_or_cell_type: Hippocampal dentate-gyrus-like neuronal progenitors\nexperimental_model: Patient-derived iPSC differentiation and rescue\nlimitations: Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.\nexposure: Biallelic IMPA1 defect and myo-inositol-supplemented medium\nevidence_span: {\"source_cache\": \"artifacts/inositol-research/32839513.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed\", \"start_char\": 0, \"end_char\": 1711, \"text_sha256\": \"5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed\"}\n[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. 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