{"id":"b6d1f48c-cc31-5c2a-8e02-6c461323b6a7","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-orai1-inherited-loss-influx","predicate":"supports","statement":"Homozygous ORAI1 R91W loss of function abolishes CRAC activity in patient T cells; wild-type ORAI1 restores influx.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"fb689c8f-5934-5e4c-b7f7-eac94f27900e","mechanism_event_label":"This inherited channel defect interrupts calcium entry into T cells.","subject":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"object":{"id":"a3169279-41ce-5c17-919f-dc7b48f6f6d6","slug":"store-operated-calcium-entry","display_name":"Store-operated calcium entry","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fb689c8f-5934-5e4c-b7f7-eac94f27900e","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-orai1-inherited-loss-influx-event","event_type":"loss_of_function","label":"This inherited channel defect interrupts calcium entry into T cells.","description":"Homozygous ORAI1 R91W loss of function abolishes CRAC activity in patient T cells; wild-type ORAI1 restores influx.","status":"provisional","compartment":{"slug":"plasma-membrane","display_name":"Plasma membrane"},"participants":[{"entity":{"id":"c214f817-afc5-567e-ae17-ab5558e88394","slug":"orai1","display_name":"ORAI1","entity_type_key":"protein"},"role":"impaired_channel","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"139d3bf7-eabf-5e39-a20c-c6498ef76a39","slug":"orai1-r91w","display_name":"ORAI1 R91W loss-of-function variant","entity_type_key":"protein_state"},"role":"loss_of_function_variant","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":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a3169279-41ce-5c17-919f-dc7b48f6f6d6","slug":"store-operated-calcium-entry","display_name":"Store-operated calcium entry","entity_type_key":"cellular_process"},"role":"affected_process","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f0b6bcb6-5d41-5d9d-af9f-6af1a94d5c5a","slug":"plasma-membrane","display_name":"Plasma membrane","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":4,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"compartment_description","value_text":"Plasma membrane","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human inherited immune deficiency, patient T-cell rescue and functional channel assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A rare channelopathy, not nutritional calcium deficiency; the evidence concerns the studied variant.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This inherited channel defect interrupts calcium entry into T cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ca-feske2006] A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function (2006). https://pubmed.ncbi.nlm.nih.gov/16582901/ DOI: 10.1038/nature04702","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"research_relationship_category","value_text":"loss_of_function","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient T lymphocytes","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":"099c73cf-1ae0-5dd8-a5a0-0722f45520fd","evidence_kind":"source_excerpt","locator":"Lines 558-569","start_line":558,"end_line":569,"excerpt":"### ca-orai1-inherited-loss-influx\nHomozygous ORAI1 R91W loss of function abolishes CRAC activity in patient T cells; wild-type ORAI1 restores influx.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This inherited channel defect interrupts calcium entry into T cells.\norganism: Homo sapiens\ntissue_or_cell_type: Patient T lymphocytes\nexperimental_model: Human inherited immune deficiency, patient T-cell rescue and functional channel assays\nlimitations: A rare channelopathy, not nutritional calcium deficiency; the evidence concerns the studied variant.\nresearch_relationship_category: loss_of_function\ncompartment_description: Plasma membrane\n[ca-feske2006] A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function (2006). https://pubmed.ncbi.nlm.nih.gov/16582901/ DOI: 10.1038/nature04702","model_system":"Human inherited immune deficiency, patient T-cell rescue and functional channel assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ca-feske2006] A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function (2006). https://pubmed.ncbi.nlm.nih.gov/16582901/ DOI: 10.1038/nature04702","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}