{"id":"c6059a83-3180-5ca0-a15a-e2f39f48643a","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp24a1-hypercalcemia","predicate":"loss_of_function_predisposes_to","statement":"Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"22f14852-2558-5d2f-adc6-005818832d9d","mechanism_event_label":"Defective vitamin D breakdown can make infants unusually sensitive to supplementation.","subject":{"id":"970c1e11-e5b9-5518-b4c1-279673b4a95e","slug":"cyp24a1-gene","display_name":"Human CYP24A1 gene","entity_type_key":"gene"},"object":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"22f14852-2558-5d2f-adc6-005818832d9d","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp24a1-hypercalcemia-event","event_type":"observed_intervention","label":"Defective vitamin D breakdown can make infants unusually sensitive to supplementation.","description":"Recessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c0a944e7-deb8-5f9e-8428-91496098e38f","slug":"cyp24a1","display_name":"Vitamin D 24-hydroxylase / CYP24A1","entity_type_key":"protein"},"role":"affected_catabolic_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f5156c24-108f-5746-b114-ed764e79a3f4","slug":"calcitriol","display_name":"Calcitriol","entity_type_key":"small_molecule"},"role":"mechanistic_hormone","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"affected_mineral","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"970c1e11-e5b9-5518-b4c1-279673b4a95e","slug":"cyp24a1-gene","display_name":"Human CYP24A1 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"068b1eb6-c8bf-59d3-98a0-df623ad01b52","slug":"serum-calcium-concentration","display_name":"Serum calcium concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human candidate-gene study with supporting enzyme assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"First cohort received 500 IU/day; second cohort became symptomatic 2-3 weeks after intermittent high-dose prophylaxis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Selected families do not estimate population risk. Genotype, dose and penetrance matter; this is not a universal safe/unsafe serum or dose threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Defective vitamin D breakdown can make infants unusually sensitive to supplementation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"systemic calcium handling","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":"e0273f6e-4c10-5fad-8dab-695bf22da56f","evidence_kind":"source_excerpt","locator":"Lines 602-615","start_line":602,"end_line":615,"excerpt":"### vd-act-cyp24a1-hypercalcemia\nRecessive CYP24A1 variants were identified in infants with hypercalcemia, including a second group whose illness followed high-dose vitamin D prophylaxis.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Defective vitamin D breakdown can make infants unusually sensitive to supplementation.\norganism: Homo sapiens\ntissue_or_cell_type: systemic calcium handling\nexperimental_model: Human candidate-gene study with supporting enzyme assays\nlimitations: Selected families do not estimate population risk. Genotype, dose and penetrance matter; this is not a universal safe/unsafe serum or dose threshold.\nexposure: First cohort received 500 IU/day; second cohort became symptomatic 2-3 weeks after intermittent high-dose prophylaxis.\ncross_nutrient: true\nevidence_location: Primary Results, in-vitro analysis and Figure 4; clinical cohorts and Discussion.\nnutrient: Vitamin D2 and D3\n[schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864","model_system":"Human candidate-gene study with supporting enzyme assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [schlingmann2011] Mutations in CYP24A1 and idiopathic infantile hypercalcemia. (2011). https://pubmed.ncbi.nlm.nih.gov/21675912/ DOI: 10.1056/NEJMoa1103864","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c95c763c-5b31-5b3f-a2f8-2dfe5ef0d3ca","stable_key":"import-1deb434a-3547-51a0-a038-87b1ce79ec38","title":"Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (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":"51004bf0d78db6146b8f198b0688a3cc7d4ea9822415a9c034f4c8790fb4e38b","revision_id":"d52ff207-a311-5f24-96f4-462838792db5","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}