{"id":"a07cc4fe-11df-50ab-b132-940a6f122607","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-losing-card9-costs-antifungal-defence","predicate":"disrupts","statement":"All four affected family members had a homozygous point mutation in CARD9 resulting in a premature termination codon Q295X, healthy family members had wild-type expression of the CARD9 protein while the four patients lacked wild-type expression which was associated with low numbers of interleukin-17-producing helper T cells, and functional studies based on genetic reconstitution of myeloid cells from Card9-null mice showed that the Q295X mutation impairs innate signalling from the antifungal pattern-recognition receptor dectin-1.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9ceb4a9c-ef06-5cfe-bc0e-c6e9a658f5eb","mechanism_event_label":"People born without this one signalling protein get persistent fungal infections, which is how much the pathway matters.","subject":{"id":"99d60f72-13a9-5b87-82c9-bbf7fd29fb86","slug":"card9-q295x","display_name":"The homozygous CARD9 Q295X premature termination variant","entity_type_key":"protein_state"},"object":{"id":"117c178c-d74c-5c56-b2d6-d3956ad70c03","slug":"clec7a","display_name":"Dectin-1 / CLEC7A","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"9ceb4a9c-ef06-5cfe-bc0e-c6e9a658f5eb","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-losing-card9-costs-antifungal-defence-event","event_type":"observed_intervention","label":"People born without this one signalling protein get persistent fungal infections, which is how much the pathway matters.","description":"All four affected family members had a homozygous point mutation in CARD9 resulting in a premature termination codon Q295X, healthy family members had wild-type expression of the CARD9 protein while the four patients lacked wild-type expression which was associated with low numbers of interleukin-17-producing helper T cells, and functional studies based on genetic reconstitution of myeloid cells from Card9-null mice showed that the Q295X mutation impairs innate signalling from the antifungal pattern-recognition receptor dectin-1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6b5084ed-884e-5163-88cd-31015178dea4","slug":"card9","display_name":"Caspase recruitment domain-containing protein 9 / CARD9","entity_type_key":"protein"},"role":"lost_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"92436533-20eb-5924-b125-e301937ec1b1","slug":"th17-cells","display_name":"Interleukin-17-producing helper T cells","entity_type_key":"cell_type"},"role":"depleted_population","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"1942f952-fa09-57bb-bb95-09b0c992ea27","slug":"chronic-mucocutaneous-candidiasis","display_name":"Chronic mucocutaneous candidiasis","entity_type_key":"cellular_process"},"role":"resulting_condition","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ffb2c379-991d-5916-ad7f-15e698f3b2b6","slug":"candida-albicans","display_name":"Candida albicans","entity_type_key":"organism"},"role":"infecting_organism","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"99d60f72-13a9-5b87-82c9-bbf7fd29fb86","slug":"card9-q295x","display_name":"The homozygous CARD9 Q295X premature termination variant","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"117c178c-d74c-5c56-b2d6-d3956ad70c03","slug":"clec7a","display_name":"Dectin-1 / CLEC7A","entity_type_key":"protein"},"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":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glucan-research/19864672.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"41fdf4ca9e34eac18be47ed10f5eec82966269f2595759bc97a485f91d746de3\", \"start_char\": 0, \"end_char\": 1842, \"text_sha256\": \"41fdf4ca9e34eac18be47ed10f5eec82966269f2595759bc97a485f91d746de3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Homozygosity mapping and sequencing in a consanguineous five-generation family with 36 members enrolled","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Naturally occurring homozygous CARD9 Q295X premature termination, with reconstitution in Card9-null mouse myeloid cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human genetics with a linkage score of 3.6 and functional confirmation. It establishes the importance of the pathway in host defence; it says nothing about beta-glucan as a supplement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.","comparator":null,"unit":null,"notes":"","entity":{"slug":"beta-glucan","display_name":"Beta-glucan","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"People born without this one signalling protein get persistent fungal infections, which is how much the pathway matters.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[bg-p19864672] A homozygous CARD9 mutation in a family with susceptibility to fungal infections. (2009). https://pubmed.ncbi.nlm.nih.gov/19864672/ DOI: 10.1056/nejmoa0810719","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Leukocytes","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":"56c3a854-0e64-5b66-ab4a-478d591cb57d","evidence_kind":"source_excerpt","locator":"Lines 411-422","start_line":411,"end_line":422,"excerpt":"### bg-losing-card9-costs-antifungal-defence\nAll four affected family members had a homozygous point mutation in CARD9 resulting in a premature termination codon Q295X, healthy family members had wild-type expression of the CARD9 protein while the four patients lacked wild-type expression which was associated with low numbers of interleukin-17-producing helper T cells, and functional studies based on genetic reconstitution of myeloid cells from Card9-null mice showed that the Q295X mutation impairs innate signalling from the antifungal pattern-recognition receptor dectin-1.\nCondition category: machinery_impairment\nnutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair.\nplain_language: People born without this one signalling protein get persistent fungal infections, which is how much the pathway matters.\norganism: Human\ntissue_or_cell_type: Leukocytes\nexperimental_model: Homozygosity mapping and sequencing in a consanguineous five-generation family with 36 members enrolled\nlimitations: Human genetics with a linkage score of 3.6 and functional confirmation. It establishes the importance of the pathway in host defence; it says nothing about beta-glucan as a supplement.\nexposure: Naturally occurring homozygous CARD9 Q295X premature termination, with reconstitution in Card9-null mouse myeloid cells\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/19864672.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"41fdf4ca9e34eac18be47ed10f5eec82966269f2595759bc97a485f91d746de3\", \"start_char\": 0, \"end_char\": 1842, \"text_sha256\": \"41fdf4ca9e34eac18be47ed10f5eec82966269f2595759bc97a485f91d746de3\"}\n[bg-p19864672] A homozygous CARD9 mutation in a family with susceptibility to fungal infections. (2009). https://pubmed.ncbi.nlm.nih.gov/19864672/ DOI: 10.1056/nejmoa0810719","model_system":"Homozygosity mapping and sequencing in a consanguineous five-generation family with 36 members enrolled","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [bg-p19864672] A homozygous CARD9 mutation in a family with susceptibility to fungal infections. (2009). https://pubmed.ncbi.nlm.nih.gov/19864672/ DOI: 10.1056/nejmoa0810719","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"74dc223d-8289-57bf-a731-d220fa017c1e","stable_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","title":"Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22)","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":"7c62f2d2f8d99b650e6dc26a505b0f053ae1c8bdb38099d4dfc0771f65287461","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}