{"gene":"FCN1","run_date":"2026-04-28T17:46:03","timeline":{"discoveries":[{"year":2009,"finding":"FCN1-encoded Ficolin-1 (M-ficolin) functions as a soluble collagen-like pattern recognition molecule that binds sugar structures or acetylated compounds on microorganisms and dying host cells, and initiates activation of the lectin complement pathway.","method":"Review of molecular and functional studies; binding and complement activation assays","journal":"Molecular immunology","confidence":"High","confidence_rationale":"Tier 2 — replicated across multiple labs, foundational highly-cited review summarizing established functional data","pmids":["19501910"],"is_preprint":false},{"year":2012,"finding":"FCN1 promoter polymorphisms at positions -542 and -144 regulate both FCN1 mRNA expression in monocytes/granulocytes and the secretion of Ficolin-1 protein, as demonstrated by allele-specific differences in mRNA levels and protein concentrations in monocyte culture supernatants.","method":"FCN1 mRNA expression in genotyped individuals, ELISA of monocyte culture supernatants, plasma ficolin-1 measurement","journal":"Genes and immunity","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (mRNA, protein secretion, plasma levels) in a single study","pmids":["22673311"],"is_preprint":false},{"year":2012,"finding":"Non-synonymous FCN1 mutations Ala218Thr (rs148649884) and Asn289Ser (rs138055828) reduce M-ficolin ligand-binding capability (to Group B Streptococcus), and Ser268Pro (rs150625869) abolishes M-ficolin production entirely, as shown by recombinant protein expression and binding assays.","method":"Recombinant protein expression, ligand-binding assays (Group B Streptococcus), genotype-phenotype correlation in 346 blood donors","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 — recombinant protein mutagenesis combined with functional binding assays and clinical validation","pmids":["23209787"],"is_preprint":false},{"year":2017,"finding":"The collagen-like domain of FCN1 (M-ficolin) directly binds IgG1 in vitro through the CH1 and CH3 domains of IgG1, as demonstrated by Western blot co-binding assays and inhibition with synthetic peptides corresponding to CH1/CH3 domains.","method":"In vitro binding assay (Western blot), recombinant domain mapping, synthetic peptide inhibition","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 — direct in vitro binding with domain-level resolution and peptide inhibition, single lab","pmids":["28900133"],"is_preprint":false},{"year":2023,"finding":"FCN1 overexpression in THP-1-derived macrophages promotes LPS-induced IL-1β maturation via the NLRP3-caspase-1 axis, placing FCN1 upstream of NLRP3 inflammasome activation in macrophage proinflammatory signaling.","method":"FCN1 overexpression in THP-1-derived macrophages, LPS stimulation, Western blot/qRT-PCR for IL-1β, NLRP3 and caspase-1 pathway analysis","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 — gain-of-function with defined pathway readout, single lab","pmids":["36932401"],"is_preprint":false}],"current_model":"FCN1-encoded Ficolin-1 (M-ficolin) is a soluble collagen-like pattern recognition molecule that binds acetylated/sugar ligands on pathogens and apoptotic cells via its fibrinogen-like domain to activate the lectin complement pathway; its collagen-like domain directly associates with the CH1/CH3 regions of IgG1; non-synonymous mutations in FCN1 impair ligand binding or abolish protein production; promoter polymorphisms at -542/-144 regulate FCN1 transcription and protein secretion in monocytes; and in macrophages FCN1 promotes IL-1β maturation through the NLRP3-caspase-1 inflammasome axis."},"narrative":{"teleology":[{"year":2009,"claim":"Establishing FCN1 as a pattern recognition molecule that activates the lectin complement pathway resolved the fundamental question of how this collagen-like lectin contributes to innate immunity.","evidence":"Synthesis of binding and complement activation assays from multiple laboratories","pmids":["19501910"],"confidence":"High","gaps":["Structural basis for ligand selectivity of the fibrinogen-like domain not resolved","Relative contribution of FCN1 versus other ficolins to complement activation in vivo unclear"]},{"year":2012,"claim":"Demonstration that promoter polymorphisms at -542 and -144 regulate FCN1 transcription and protein secretion in monocytes established that genetic variation controls Ficolin-1 availability at the expression level.","evidence":"Allele-specific mRNA quantification, ELISA of monocyte supernatants, and plasma Ficolin-1 measurement in genotyped individuals","pmids":["22673311"],"confidence":"Medium","gaps":["Transcription factor(s) binding at -542/-144 not identified","Functional consequences of reduced Ficolin-1 levels on complement activation not measured"]},{"year":2012,"claim":"Identification of non-synonymous FCN1 mutations that impair ligand binding or abolish protein production demonstrated that coding-region variants directly compromise Ficolin-1 function at the protein level.","evidence":"Recombinant mutagenesis, Group B Streptococcus binding assays, and genotype–phenotype correlation in 346 blood donors","pmids":["23209787"],"confidence":"High","gaps":["Structural mechanism by which Ala218Thr and Asn289Ser reduce binding affinity not determined","Clinical disease associations of these variants not established in prospective cohorts"]},{"year":2017,"claim":"Mapping a direct interaction between the collagen-like domain of Ficolin-1 and IgG1 CH1/CH3 regions revealed an unexpected link between the lectin pathway and adaptive humoral immunity.","evidence":"In vitro Western blot co-binding assays, recombinant domain mapping, and synthetic peptide inhibition","pmids":["28900133"],"confidence":"Medium","gaps":["Physiological relevance of the FCN1–IgG1 interaction (e.g., opsonization enhancement, immune complex clearance) not demonstrated in vivo","Binding affinity and stoichiometry not quantified by biophysical methods"]},{"year":2023,"claim":"Showing that FCN1 overexpression promotes LPS-induced IL-1β maturation via the NLRP3–caspase-1 axis placed Ficolin-1 upstream of inflammasome activation, expanding its role beyond complement to macrophage inflammatory signaling.","evidence":"FCN1 overexpression in THP-1-derived macrophages with LPS stimulation; Western blot and qRT-PCR for NLRP3 pathway components","pmids":["36932401"],"confidence":"Medium","gaps":["Mechanism by which FCN1 activates NLRP3 (direct interaction vs. upstream signaling intermediate) not identified","Loss-of-function validation (knockout/knockdown) not reported","Relevance confirmed only in a single cell line model"]},{"year":null,"claim":"The direct molecular mechanism linking Ficolin-1 to NLRP3 inflammasome assembly, the physiological significance of the FCN1–IgG1 interaction in vivo, and the structural basis for ligand discrimination by the fibrinogen-like domain remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of Ficolin-1 fibrinogen-like domain bound to a natural ligand","In vivo loss-of-function models for FCN1 not reported in the literature","Whether FCN1–IgG1 binding modulates adaptive immune responses is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,2,4]}],"complexes":[],"partners":["NLRP3","CASP1"],"other_free_text":[]},"mechanistic_narrative":"FCN1 encodes Ficolin-1 (M-ficolin), a soluble collagen-like pattern recognition receptor that binds acetylated compounds and sugar structures on microorganisms and apoptotic cells via its fibrinogen-like domain, thereby initiating the lectin complement pathway [PMID:19501910]. Non-synonymous mutations such as Ala218Thr and Asn289Ser impair ligand binding to pathogens like Group B Streptococcus, while Ser268Pro abolishes protein production entirely [PMID:23209787]. Beyond complement activation, the collagen-like domain of Ficolin-1 directly interacts with the CH1/CH3 regions of IgG1, and in macrophages FCN1 promotes LPS-induced IL-1β maturation through the NLRP3–caspase-1 inflammasome axis [PMID:28900133, PMID:36932401]."},"prefetch_data":{"uniprot":{"accession":"O00602","full_name":"Ficolin-1","aliases":["Collagen/fibrinogen domain-containing protein 1","Ficolin-A","Ficolin-alpha","M-ficolin"],"length_aa":326,"mass_kda":35.1,"function":"Extracellular lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:16116205, PubMed:17897951, PubMed:20032467). Specifically recognizes and binds carbohydrates on the pathogen surface, activating the MASP1 serine protease and initiating the proteolytic cascade of the lectin complement pathway (PubMed:16116205, PubMed:20032467). Binds preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage (PubMed:20032467, PubMed:20400674). May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8 (PubMed:21037097)","subcellular_location":"Secreted; Cell surface","url":"https://www.uniprot.org/uniprotkb/O00602/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FCN1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/FCN1","total_profiled":1310},"omim":[{"mim_id":"613357","title":"FIBRINOGEN C DOMAIN-CONTAINING PROTEIN 1; FIBCD1","url":"https://www.omim.org/entry/613357"},{"mim_id":"604973","title":"FICOLIN 3; FCN3","url":"https://www.omim.org/entry/604973"},{"mim_id":"601624","title":"FICOLIN 2; FCN2","url":"https://www.omim.org/entry/601624"},{"mim_id":"601252","title":"FICOLIN 1; FCN1","url":"https://www.omim.org/entry/601252"},{"mim_id":"301110","title":"HEMOLYTIC UREMIC SYNDROME, ATYPICAL, 8, WITH RHIZOMELIC SHORT STATURE; AHUS8","url":"https://www.omim.org/entry/301110"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":150.0},{"tissue":"lymphoid tissue","ntpm":45.0}],"url":"https://www.proteinatlas.org/search/FCN1"},"hgnc":{"alias_symbol":["FCNM"],"prev_symbol":[]},"alphafold":{"accession":"O00602","domains":[{"cath_id":"3.90.215.10","chopping":"119-261_317-326","consensus_level":"high","plddt":98.2256,"start":119,"end":326}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00602","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00602-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00602-F1-predicted_aligned_error_v6.png","plddt_mean":84.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FCN1","jax_strain_url":"https://www.jax.org/strain/search?query=FCN1"},"sequence":{"accession":"O00602","fasta_url":"https://rest.uniprot.org/uniprotkb/O00602.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00602/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00602"}},"corpus_meta":[{"pmid":"19501910","id":"PMC_19501910","title":"MBL2, FCN1, FCN2 and FCN3-The genes behind the initiation of the lectin pathway of complement.","date":"2009","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19501910","citation_count":121,"is_preprint":false},{"pmid":"22673311","id":"PMC_22673311","title":"Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation.","date":"2012","source":"Genes and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/22673311","citation_count":64,"is_preprint":false},{"pmid":"18032536","id":"PMC_18032536","title":"Polymorphisms in the ficolin 1 gene (FCN1) are associated with susceptibility to the development of rheumatoid arthritis.","date":"2007","source":"Rheumatology (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/18032536","citation_count":52,"is_preprint":false},{"pmid":"36932401","id":"PMC_36932401","title":"Identification of FCN1 as a novel macrophage infiltration-associated biomarker for diagnosis of pediatric inflammatory bowel diseases.","date":"2023","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36932401","citation_count":32,"is_preprint":false},{"pmid":"23209787","id":"PMC_23209787","title":"Non-synonymous polymorphisms in the FCN1 gene determine ligand-binding ability and serum levels of M-ficolin.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23209787","citation_count":23,"is_preprint":false},{"pmid":"28900133","id":"PMC_28900133","title":"FCN1 (M-ficolin), which directly associates with immunoglobulin G1, is a molecular target of intravenous immunoglobulin therapy for Kawasaki disease.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28900133","citation_count":16,"is_preprint":false},{"pmid":"39402337","id":"PMC_39402337","title":"FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1hi macrophages and aggravates pulmonary pathology in severe COVID-19.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39402337","citation_count":12,"is_preprint":false},{"pmid":"32142211","id":"PMC_32142211","title":"Ficolin-1 gene (FCN1) -144 C/A polymorphism is associated with adverse outcome of severe pneumonia in the under-five Egyptian children: A multicenter study.","date":"2020","source":"Pediatric pulmonology","url":"https://pubmed.ncbi.nlm.nih.gov/32142211","citation_count":8,"is_preprint":false},{"pmid":"38262391","id":"PMC_38262391","title":"Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.","date":"2024","source":"Allergy, asthma & immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/38262391","citation_count":7,"is_preprint":false},{"pmid":"36569030","id":"PMC_36569030","title":"Effect of Polymorphisms in the FCN1, FCN2, and FCN3 Genes on the Susceptibility to Develop Rheumatoid Arthritis: A Systematic Review.","date":"2022","source":"International journal of rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/36569030","citation_count":5,"is_preprint":false},{"pmid":"33600013","id":"PMC_33600013","title":"FCN1 polymorphisms are not the markers of dental caries susceptibility in Polish children: A case-control study.","date":"2021","source":"Oral diseases","url":"https://pubmed.ncbi.nlm.nih.gov/33600013","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7464,"output_tokens":1222,"usd":0.020361},"stage2":{"model":"claude-opus-4-6","input_tokens":4452,"output_tokens":1557,"usd":0.091777},"total_usd":0.112138,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"FCN1-encoded Ficolin-1 (M-ficolin) functions as a soluble collagen-like pattern recognition molecule that binds sugar structures or acetylated compounds on microorganisms and dying host cells, and initiates activation of the lectin complement pathway.\",\n      \"method\": \"Review of molecular and functional studies; binding and complement activation assays\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — replicated across multiple labs, foundational highly-cited review summarizing established functional data\",\n      \"pmids\": [\"19501910\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"FCN1 promoter polymorphisms at positions -542 and -144 regulate both FCN1 mRNA expression in monocytes/granulocytes and the secretion of Ficolin-1 protein, as demonstrated by allele-specific differences in mRNA levels and protein concentrations in monocyte culture supernatants.\",\n      \"method\": \"FCN1 mRNA expression in genotyped individuals, ELISA of monocyte culture supernatants, plasma ficolin-1 measurement\",\n      \"journal\": \"Genes and immunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (mRNA, protein secretion, plasma levels) in a single study\",\n      \"pmids\": [\"22673311\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Non-synonymous FCN1 mutations Ala218Thr (rs148649884) and Asn289Ser (rs138055828) reduce M-ficolin ligand-binding capability (to Group B Streptococcus), and Ser268Pro (rs150625869) abolishes M-ficolin production entirely, as shown by recombinant protein expression and binding assays.\",\n      \"method\": \"Recombinant protein expression, ligand-binding assays (Group B Streptococcus), genotype-phenotype correlation in 346 blood donors\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — recombinant protein mutagenesis combined with functional binding assays and clinical validation\",\n      \"pmids\": [\"23209787\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The collagen-like domain of FCN1 (M-ficolin) directly binds IgG1 in vitro through the CH1 and CH3 domains of IgG1, as demonstrated by Western blot co-binding assays and inhibition with synthetic peptides corresponding to CH1/CH3 domains.\",\n      \"method\": \"In vitro binding assay (Western blot), recombinant domain mapping, synthetic peptide inhibition\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct in vitro binding with domain-level resolution and peptide inhibition, single lab\",\n      \"pmids\": [\"28900133\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FCN1 overexpression in THP-1-derived macrophages promotes LPS-induced IL-1β maturation via the NLRP3-caspase-1 axis, placing FCN1 upstream of NLRP3 inflammasome activation in macrophage proinflammatory signaling.\",\n      \"method\": \"FCN1 overexpression in THP-1-derived macrophages, LPS stimulation, Western blot/qRT-PCR for IL-1β, NLRP3 and caspase-1 pathway analysis\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — gain-of-function with defined pathway readout, single lab\",\n      \"pmids\": [\"36932401\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FCN1-encoded Ficolin-1 (M-ficolin) is a soluble collagen-like pattern recognition molecule that binds acetylated/sugar ligands on pathogens and apoptotic cells via its fibrinogen-like domain to activate the lectin complement pathway; its collagen-like domain directly associates with the CH1/CH3 regions of IgG1; non-synonymous mutations in FCN1 impair ligand binding or abolish protein production; promoter polymorphisms at -542/-144 regulate FCN1 transcription and protein secretion in monocytes; and in macrophages FCN1 promotes IL-1β maturation through the NLRP3-caspase-1 inflammasome axis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"FCN1 encodes Ficolin-1 (M-ficolin), a soluble collagen-like pattern recognition receptor that binds acetylated compounds and sugar structures on microorganisms and apoptotic cells via its fibrinogen-like domain, thereby initiating the lectin complement pathway [PMID:19501910]. Non-synonymous mutations such as Ala218Thr and Asn289Ser impair ligand binding to pathogens like Group B Streptococcus, while Ser268Pro abolishes protein production entirely [PMID:23209787]. Beyond complement activation, the collagen-like domain of Ficolin-1 directly interacts with the CH1/CH3 regions of IgG1, and in macrophages FCN1 promotes LPS-induced IL-1β maturation through the NLRP3–caspase-1 inflammasome axis [PMID:28900133, PMID:36932401].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing FCN1 as a pattern recognition molecule that activates the lectin complement pathway resolved the fundamental question of how this collagen-like lectin contributes to innate immunity.\",\n      \"evidence\": \"Synthesis of binding and complement activation assays from multiple laboratories\",\n      \"pmids\": [\"19501910\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis for ligand selectivity of the fibrinogen-like domain not resolved\",\n        \"Relative contribution of FCN1 versus other ficolins to complement activation in vivo unclear\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstration that promoter polymorphisms at -542 and -144 regulate FCN1 transcription and protein secretion in monocytes established that genetic variation controls Ficolin-1 availability at the expression level.\",\n      \"evidence\": \"Allele-specific mRNA quantification, ELISA of monocyte supernatants, and plasma Ficolin-1 measurement in genotyped individuals\",\n      \"pmids\": [\"22673311\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Transcription factor(s) binding at -542/-144 not identified\",\n        \"Functional consequences of reduced Ficolin-1 levels on complement activation not measured\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identification of non-synonymous FCN1 mutations that impair ligand binding or abolish protein production demonstrated that coding-region variants directly compromise Ficolin-1 function at the protein level.\",\n      \"evidence\": \"Recombinant mutagenesis, Group B Streptococcus binding assays, and genotype–phenotype correlation in 346 blood donors\",\n      \"pmids\": [\"23209787\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural mechanism by which Ala218Thr and Asn289Ser reduce binding affinity not determined\",\n        \"Clinical disease associations of these variants not established in prospective cohorts\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Mapping a direct interaction between the collagen-like domain of Ficolin-1 and IgG1 CH1/CH3 regions revealed an unexpected link between the lectin pathway and adaptive humoral immunity.\",\n      \"evidence\": \"In vitro Western blot co-binding assays, recombinant domain mapping, and synthetic peptide inhibition\",\n      \"pmids\": [\"28900133\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Physiological relevance of the FCN1–IgG1 interaction (e.g., opsonization enhancement, immune complex clearance) not demonstrated in vivo\",\n        \"Binding affinity and stoichiometry not quantified by biophysical methods\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showing that FCN1 overexpression promotes LPS-induced IL-1β maturation via the NLRP3–caspase-1 axis placed Ficolin-1 upstream of inflammasome activation, expanding its role beyond complement to macrophage inflammatory signaling.\",\n      \"evidence\": \"FCN1 overexpression in THP-1-derived macrophages with LPS stimulation; Western blot and qRT-PCR for NLRP3 pathway components\",\n      \"pmids\": [\"36932401\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which FCN1 activates NLRP3 (direct interaction vs. upstream signaling intermediate) not identified\",\n        \"Loss-of-function validation (knockout/knockdown) not reported\",\n        \"Relevance confirmed only in a single cell line model\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular mechanism linking Ficolin-1 to NLRP3 inflammasome assembly, the physiological significance of the FCN1–IgG1 interaction in vivo, and the structural basis for ligand discrimination by the fibrinogen-like domain remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of Ficolin-1 fibrinogen-like domain bound to a natural ligand\",\n        \"In vivo loss-of-function models for FCN1 not reported in the literature\",\n        \"Whether FCN1–IgG1 binding modulates adaptive immune responses is untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 2, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"NLRP3\",\n      \"CASP1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}