{"id":"fb18c0cb-fd34-5330-adb5-617668ac9d19","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:cldn12-calcium-permeability","predicate":"supports","statement":"Claudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"fc05b50a-febf-5856-b447-756be2f6e6b3","mechanism_event_label":"Claudin-12 contributes another between-cell route.","subject":{"id":"e6ebb895-0787-5d8b-8aca-1b5e2f827366","slug":"cldn12","display_name":"Claudin-12","entity_type_key":"protein"},"object":{"id":"2e5a14d0-255a-56c0-9c0f-5bbb8cd09daa","slug":"paracellular-calcium-permeability","display_name":"Paracellular calcium permeability","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fc05b50a-febf-5856-b447-756be2f6e6b3","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:cldn12-calcium-permeability-event","event_type":"biochemical_relationship","label":"Claudin-12 contributes another between-cell route.","description":"Claudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e6ebb895-0787-5d8b-8aca-1b5e2f827366","slug":"cldn12","display_name":"Claudin-12","entity_type_key":"protein"},"role":"paracellular_component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"permeant","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"2e5a14d0-255a-56c0-9c0f-5bbb8cd09daa","slug":"paracellular-calcium-permeability","display_name":"Paracellular calcium permeability","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay context matters; this does not prove a mandatory claudin-2/12 complex.","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":"Homo sapiens cell line","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Claudin-12 contributes another between-cell route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Caco-2 epithelial tight junctions","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d4655a4a-0334-528b-a26a-7cda7679f300","evidence_kind":"source_excerpt","locator":"Lines 203-212","start_line":203,"end_line":212,"excerpt":"### cldn12-calcium-permeability\nClaudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Claudin-12 contributes another between-cell route.\norganism: Homo sapiens cell line\ntissue_or_cell_type: Caco-2 epithelial tight junctions\nexperimental_model: Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression\nlimitations: Assay context matters; this does not prove a mandatory claudin-2/12 complex.\n[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973","model_system":"Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973","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":[{"id":"227f4de1-3b2e-598c-a17b-7e709347b7ff","title":"Claudin permeability effects depend on epithelial context","kind":"context_difference","status":"qualified","why":"Caco-2 assays implicate claudin-2/12; double-null mouse permeability changes localized to colon rather than small intestine.","resolution":"Curation interpretation: Retain cell-line versus intact-segment distinctions and parallel pore redundancy.","created_at":"2026-09-17 08:08:54","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/227f4de1-3b2e-598c-a17b-7e709347b7ff","sides":[{"conflict_id":"227f4de1-3b2e-598c-a17b-7e709347b7ff","ordinal":0,"label":"Claudin-2 supports calcium movement between cells.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":192,"end_line":201,"quote":"### cldn2-calcium-permeability\nClaudin-2 manipulation changes calcium permeability across Caco-2 epithelial monolayers.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Claudin-2 supports calcium movement between cells.\norganism: Homo sapiens cell line\ntissue_or_cell_type: Caco-2 epithelial tight junctions\nexperimental_model: Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression\nlimitations: Cell-line permeability; not an obligatory route in every intestinal segment.\n[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["6148319f-4c12-5830-9c8d-00adf29564fa"]},{"conflict_id":"227f4de1-3b2e-598c-a17b-7e709347b7ff","ordinal":1,"label":"Claudin-12 contributes another between-cell route.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":203,"end_line":212,"quote":"### cldn12-calcium-permeability\nClaudin-12 knockdown/overexpression alters calcium permeability in Caco-2 monolayers.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Claudin-12 contributes another between-cell route.\norganism: Homo sapiens cell line\ntissue_or_cell_type: Caco-2 epithelial tight junctions\nexperimental_model: Caco-2 knockdown/overexpression and mouse VDR-null intestinal expression\nlimitations: Assay context matters; this does not prove a mandatory claudin-2/12 complex.\n[fujita2008] Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2366872/ DOI: 10.1091/mbc.E07-09-0973","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["fb18c0cb-fd34-5330-adb5-617668ac9d19"]},{"conflict_id":"227f4de1-3b2e-598c-a17b-7e709347b7ff","ordinal":2,"label":"The measured defect was segment specific.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":214,"end_line":223,"quote":"### cldn2-cldn12-double-loss-colon\nCldn2/Cldn12 double deletion lowers colonic calcium permeability; small-intestinal permeability was unchanged.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The measured defect was segment specific.\norganism: Mus musculus\ntissue_or_cell_type: Colon\nexperimental_model: Cldn2/Cldn12 single/double knockout mice, ex vivo epithelia and cell models\nlimitations: Global double knockout; single proteins are partly redundant.\n[beggs2021] Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8694054/ DOI: 10.1073/pnas.2111247118","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["072b7b20-229e-5abf-9fd1-c3bc15f1165c"]}]}],"research":null}