{"id":"73cd169a-0cf1-5d20-a2c2-7f480d3c7251","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:phospho1-alpl-double-loss-mineralization","predicate":"cooperates_with","statement":"Combined loss of PHOSPHO1 and ALPL prevented skeletal mineralization in the reported double-null mouse embryos.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"7d8efb46-6d0b-580a-bb8e-2c118d4930db","mechanism_event_label":"These phosphate-handling enzymes provide complementary support for mineral formation.","subject":{"id":"bb7ed19e-2f65-5951-8963-40d6b3249b71","slug":"phospho1","display_name":"Phosphoethanolamine/phosphocholine phosphatase PHOSPHO1","entity_type_key":"protein"},"object":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"7d8efb46-6d0b-580a-bb8e-2c118d4930db","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:phospho1-alpl-double-loss-mineralization-event","event_type":"biochemical_relationship","label":"These phosphate-handling enzymes provide complementary support for mineral formation.","description":"Combined loss of PHOSPHO1 and ALPL prevented skeletal mineralization in the reported double-null mouse embryos.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bb7ed19e-2f65-5951-8963-40d6b3249b71","slug":"phospho1","display_name":"Phosphoethanolamine/phosphocholine phosphatase PHOSPHO1","entity_type_key":"protein"},"role":"deleted_intravesicular_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"deleted_extracellular_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0da3fbd1-7438-5d0a-954d-f059bd3d22a9","slug":"matrix-vesicle","display_name":"Mineralizing matrix vesicle","entity_type_key":"organelle"},"role":"mineralization_site","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f8b4bc7f-edd0-511e-a3b3-c0191d216959","slug":"skeletal-mineralization","display_name":"Skeletal matrix mineralization","entity_type_key":"cellular_process"},"role":"impaired_outcome","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":"experimental_model","value_text":"Phospho1/Alpl double-null embryos","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Severe genetic disruption is not equivalent to low dietary calcium; isolated exceptions and developmental timing matter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"These phosphate-handling enzymes provide complementary support for mineral formation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[yadav2011] Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification (2011). https://pubmed.ncbi.nlm.nih.gov/20684022/ DOI: 10.1002/jbmr.195","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Developing skeleton","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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Study references: [yadav2011] Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification (2011). https://pubmed.ncbi.nlm.nih.gov/20684022/ DOI: 10.1002/jbmr.195","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}