{"id":"2f226b9d-164f-5002-bc5c-b4e0da5f80ca","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cubilin-human-loss","predicate":"dysfunction_increases","statement":"Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f9f173ec-b64d-5454-84f3-9d4b48aeb438","mechanism_event_label":"Cubilin defects can cause loss of vitamin D precursor through urine.","subject":{"id":"1aaedb79-b0cc-5184-9e46-f859ecbf78db","slug":"cubn-gene","display_name":"Human CUBN gene","entity_type_key":"gene"},"object":{"id":"b51960e5-4277-547b-9871-6f7741ef8516","slug":"urinary-calcifediol-loss","display_name":"Urinary loss of calcifediol","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f9f173ec-b64d-5454-84f3-9d4b48aeb438","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cubilin-human-loss-event","event_type":"observed_intervention","label":"Cubilin defects can cause loss of vitamin D precursor through urine.","description":"Human patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7a3dab53-fbcd-58da-9942-21f1a3ed088d","slug":"cubn","display_name":"Human cubilin / CUBN","entity_type_key":"protein"},"role":"affected_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ac7c6f66-5489-5d3a-899f-b1f4f08a5f0a","slug":"gc","display_name":"Human vitamin D-binding protein / GC","entity_type_key":"protein"},"role":"carrier","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6bd73bd2-1f0a-5caa-ba69-7ce1b75364bb","slug":"calcifediol","display_name":"Calcifediol / 25-hydroxyvitamin D3","entity_type_key":"small_molecule"},"role":"lost_cargo","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"shared_transporter_context","stoichiometry":null,"state_label":"","sequence_order":3,"notes":"Cubilin participates in B12 uptake; this study does not establish a dietary B12-to-D causal effect."},{"entity":{"id":"1aaedb79-b0cc-5184-9e46-f859ecbf78db","slug":"cubn-gene","display_name":"Human CUBN gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"b51960e5-4277-547b-9871-6f7741ef8516","slug":"urinary-calcifediol-loss","display_name":"Urinary loss of calcifediol","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"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 abstract, cubilin sequestration and human urinary loss.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human inherited cubilin dysfunction; supporting receptor experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational.","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":"Cubilin defects can cause loss of vitamin D precursor through urine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"kidney proximal tubule and urine","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":"b7e017c1-4089-5922-9288-f2596abc250d","evidence_kind":"source_excerpt","locator":"Lines 257-270","start_line":257,"end_line":270,"excerpt":"### vd-act-cubilin-human-loss\nHuman patients with mutations causing cubilin dysfunction excreted calcifediol in urine, supporting the cubilin-dependent renal carrier-retrieval pathway.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Cubilin defects can cause loss of vitamin D precursor through urine.\norganism: Homo sapiens\ntissue_or_cell_type: kidney proximal tubule and urine\nexperimental_model: Human inherited cubilin dysfunction; supporting receptor experiments\nlimitations: This shared B12/D transport machinery does not mean dietary B12 deficiency causes urinary D loss. Genotype-phenotype evidence is observational.\nexposure: Inherited CUBN dysfunction; patient details/doses not specified in retrieved abstract.\ncross_nutrient: true\nevidence_location: Primary abstract, cubilin sequestration and human urinary loss.\nnutrient: Vitamin D2 and D3\n[nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998","model_system":"Human inherited cubilin dysfunction; supporting receptor experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [nykjaer2001] Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). (2001). https://pubmed.ncbi.nlm.nih.gov/11717447/ DOI: 10.1073/pnas.241516998","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}