{"id":"f05b64cd-56d4-503d-91d2-f42ff8de7f5c","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-amn-human-receptor","predicate":"reduces","statement":"Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ef5d5122-08ed-5b33-b971-8384ff28c1b3","mechanism_event_label":"Faulty amnionless reduced available receptor without changing its affinity.","subject":{"id":"1633ffd4-b27e-57d6-896d-3942ceaadb5e","slug":"human-amn-q248x-splice-genotype","display_name":"Human AMN p.Gln248Ter / c.208-2A>G compound genotype","entity_type_key":"gene"},"object":{"id":"d47affcb-2c7c-5fae-be8e-a13aba516e44","slug":"urinary-cubn-receptor-activity","display_name":"Urinary cubilin intrinsic factor-binding activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ef5d5122-08ed-5b33-b971-8384ff28c1b3","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-amn-human-receptor-event","event_type":"observed_intervention","label":"Faulty amnionless reduced available receptor without changing its affinity.","description":"Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bbd594ac-365b-507f-954d-20a0df38312d","slug":"amn","display_name":"Human amnionless / AMN","entity_type_key":"protein"},"role":"encoded-protein","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7a3dab53-fbcd-58da-9942-21f1a3ed088d","slug":"cubn","display_name":"Human cubilin / CUBN","entity_type_key":"protein"},"role":"receptor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1633ffd4-b27e-57d6-896d-3942ceaadb5e","slug":"human-amn-q248x-splice-genotype","display_name":"Human AMN p.Gln248Ter / c.208-2A>G compound genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d47affcb-2c7c-5fae-be8e-a13aba516e44","slug":"urinary-cubn-receptor-activity","display_name":"Urinary cubilin intrinsic factor-binding activity","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":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two affected siblings and family carriers; urinary receptor characterization","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited compound AMN nonsense/splice genotype","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Faulty amnionless reduced available receptor without changing its affinity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Renal epithelial receptor expression","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":"ff15b18d-7fd4-570a-acd8-43b58b5e7c6e","evidence_kind":"source_excerpt","locator":"Lines 296-307","start_line":296,"end_line":307,"excerpt":"### b12-abs-amn-human-receptor\nTwo siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Faulty amnionless reduced available receptor without changing its affinity.\norganism: Homo sapiens\ntissue_or_cell_type: Renal epithelial receptor expression\nexperimental_model: Two affected siblings and family carriers; urinary receptor characterization\nlimitations: Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected.\nexposure: Inherited compound AMN nonsense/splice genotype\ncross_nutrient: false\n[namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984","model_system":"Two affected siblings and family carriers; urinary receptor characterization","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}