{"gene":"MS4A2","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2014,"finding":"GATA2 directly transactivates the MS4A2 (FcεRIβ) promoter via direct binding, as demonstrated by chromatin immunoprecipitation showing GATA2 binding to the MS4A2 promoter, luciferase reporter assay, and EMSA. Knockdown of GATA2 by siRNA in the human mast cell line LAD2 reduced MS4A2/FcεRIβ mRNA levels and suppressed IgE-mediated degranulation.","method":"siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assay, EMSA, flow cytometry for cell surface FcεRI","journal":"Journal of immunology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (ChIP, EMSA, luciferase assay, siRNA knockdown with functional degranulation readout) in a single rigorous study","pmids":["24639354"],"is_preprint":false},{"year":2019,"finding":"In mouse mast cells, GATA2 and PU.1 cooperatively but through distinct mechanisms activate Ms4a2 (FcεRIβ) gene expression. GATA2 exclusively binds the proximal −60-bp promoter region in a mast cell-specific manner, while both GATA2 and PU.1 share binding at a +10.4-kbp downstream enhancer region together with the chromatin looping factor LDB1. Deletion of the +10.4-kbp region by genome editing completely abolished Ms4a2 expression and cell surface FcεRI expression. PU.1 ablation reduced GATA2 binding at both regions, indicating PU.1 facilitates active chromatin structure for GATA2 access.","method":"Chromatin immunoprecipitation (ChIP), genome editing (deletion of +10.4-kbp region), siRNA knockdown, flow cytometry for FcεRI surface expression","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — genome editing with functional readout combined with ChIP and siRNA, multiple orthogonal methods in one rigorous study","pmids":["31501274"],"is_preprint":false},{"year":2006,"finding":"Luciferase reporter assays showed that the FCER1B −109T allele is associated with higher promoter activity of MS4A2 compared to the −109C allele in both RBL-2H3 and A549 cell lines, indicating that this promoter polymorphism functionally affects MS4A2 transcriptional activity.","method":"Luciferase reporter assay in RBL-2H3 and A549 cell lines","journal":"Clinical and experimental allergy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay in two cell lines, single lab, single method type","pmids":["16839402"],"is_preprint":false},{"year":2009,"finding":"The FCER1B −109T allele was associated with reduced FcεRIβ transcript levels measured in peripheral blood from human subjects, suggesting a promoter-dependent mechanism of transcriptional regulation of MS4A2.","method":"mRNA quantification correlated with promoter genotype in human subjects","journal":"International archives of allergy and immunology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, small sample (15 individuals), single method, no functional reconstitution","pmids":["19218813"],"is_preprint":false},{"year":2023,"finding":"Single-cell transcriptomic mapping localized MS4A2 expression to tumor-associated mast cells in lung adenocarcinoma, where MS4A2-high expression was associated with bidirectional chemokine regulation (suppressing CCL19/CCL21 while amplifying CCL20/CXCL8), suggesting a role in orchestrating leukocyte transendothelial migration.","method":"Single-cell RNA sequencing (scRNA-seq), bulk RNA-seq (TCGA/GTEx), immune infiltration analysis","journal":"International journal of surgery","confidence":"Low","confidence_rationale":"Tier 3 / Weak — computational/transcriptomic analysis only, no direct functional experiment on MS4A2 protein activity, single study","pmids":["40607924"],"is_preprint":false}],"current_model":"MS4A2 (FcεRIβ) is the β-chain of the high-affinity IgE receptor (FcεRI) expressed on mast cells; its transcription is directly activated by GATA2 binding to the proximal promoter and to a critical +10.4-kbp downstream enhancer (together with PU.1 and LDB1 in a chromatin loop), with PU.1 facilitating active chromatin structure that enables GATA2 access, and together these factors drive FcεRI surface expression and IgE-mediated degranulation; additionally, a common promoter polymorphism (−109T/C) modulates MS4A2 promoter activity and FcεRIβ transcript levels."},"narrative":{"mechanistic_narrative":"MS4A2 encodes the FcεRIβ chain of the high-affinity IgE receptor expressed on mast cells, where its expression is required for cell-surface FcεRI display and IgE-mediated degranulation [PMID:24639354]. Transcription is driven by GATA2, which binds the proximal MS4A2 promoter and directly transactivates the gene; GATA2 knockdown lowers FcεRIβ mRNA and suppresses IgE-triggered degranulation [PMID:24639354]. GATA2 acts together with PU.1 through distinct but cooperative mechanisms: GATA2 binds the proximal −60-bp promoter in a mast cell-specific manner, while both GATA2 and PU.1 occupy a +10.4-kbp downstream enhancer alongside the chromatin-looping factor LDB1, with PU.1 establishing active chromatin that enables GATA2 access; deletion of the +10.4-kbp enhancer abolishes both Ms4a2 expression and surface FcεRI [PMID:31501274]. A common −109T/C promoter polymorphism modulates MS4A2 promoter activity, with the −109T allele conferring higher transcriptional activity [PMID:16839402]. Beyond this transcriptional control of FcεRIβ in mast cells, the protein's own signaling biochemistry is not characterized in the available corpus.","teleology":[{"year":2006,"claim":"Whether sequence variation in the MS4A2 promoter functionally alters its transcription was unknown; this established that the −109T allele drives higher promoter activity than the −109C allele.","evidence":"Luciferase reporter assays comparing alleles in RBL-2H3 and A549 cell lines","pmids":["16839402"],"confidence":"Medium","gaps":["Single method type in one lab","No endogenous chromatin or transcription factor binding context for the variant","Functional consequence for FcεRI surface expression not tested"]},{"year":2009,"claim":"To test whether the promoter genotype predicts transcript abundance in vivo, this correlated the −109T allele with reduced FcεRIβ mRNA in human peripheral blood.","evidence":"mRNA quantification correlated with promoter genotype in human subjects","pmids":["19218813"],"confidence":"Low","gaps":["Single small cohort (15 individuals), no functional reconstitution","Direction relative to reporter findings not mechanistically reconciled","No causal manipulation"]},{"year":2014,"claim":"The trans-acting factor controlling MS4A2 was unresolved; this identified GATA2 as a direct transcriptional activator whose loss impairs FcεRI-driven mast cell function.","evidence":"ChIP, EMSA, luciferase reporter, and siRNA knockdown with degranulation readout in human LAD2 mast cells","pmids":["24639354"],"confidence":"High","gaps":["Cooperating factors and distal regulatory elements not yet defined","Mechanism of mast cell-specific promoter selection unaddressed"]},{"year":2019,"claim":"How GATA2 achieves mast cell-specific, locus-wide activation was unknown; this resolved a two-element architecture in which GATA2 binds the proximal promoter while GATA2/PU.1/LDB1 cooperate at an essential +10.4-kbp enhancer.","evidence":"ChIP, genome-editing deletion of the +10.4-kbp enhancer, and siRNA in mouse mast cells with FcεRI surface readout","pmids":["31501274"],"confidence":"High","gaps":["Direct LDB1-mediated loop topology not structurally resolved","Human enhancer equivalence to mouse +10.4-kbp element not established","Integration with −109 promoter variant unexplored"]},{"year":2023,"claim":"Whether MS4A2 marks functionally distinct mast cell states in disease was unaddressed; this localized MS4A2-high tumor-associated mast cells and correlated them with bidirectional chemokine regulation in lung adenocarcinoma.","evidence":"Single-cell and bulk RNA-seq with immune infiltration analysis","pmids":["40607924"],"confidence":"Low","gaps":["Computational/transcriptomic only, no functional test of MS4A2 protein activity","Causal role of MS4A2 in chemokine output not demonstrated","Single study"]},{"year":null,"claim":"The signaling biochemistry of the FcεRIβ protein itself — its partners, membrane assembly, and contribution to receptor signal amplification — remains uncharacterized in this corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct protein-level interaction or signaling data in the timeline","No structural model of the receptor complex"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0]}],"complexes":["FcεRI (high-affinity IgE receptor)"],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q01362","full_name":"High affinity immunoglobulin epsilon receptor subunit beta","aliases":["Fc epsilon receptor I beta-chain","IgE Fc receptor subunit beta","Membrane-spanning 4-domains subfamily A member 2"],"length_aa":244,"mass_kda":26.5,"function":"High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. Also mediates the secretion of important lymphokines. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators responsible for the manifestations of allergy","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q01362/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MS4A2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MS4A2","total_profiled":1310},"omim":[{"mim_id":"609632","title":"GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE DOMAIN-CONTAINING PROTEIN 5; GDPD5","url":"https://www.omim.org/entry/609632"},{"mim_id":"606549","title":"MEMBRANE-SPANNING 4-DOMAINS, SUBFAMILY A, MEMBER 8B; MS4A8B","url":"https://www.omim.org/entry/606549"},{"mim_id":"606548","title":"MEMBRANE-SPANNING 4-DOMAINS, SUBFAMILY A, MEMBER 6A; MS4A6A","url":"https://www.omim.org/entry/606548"},{"mim_id":"606547","title":"MEMBRANE-SPANNING 4-DOMAINS, SUBFAMILY A, MEMBER 4A; MS4A4A","url":"https://www.omim.org/entry/606547"},{"mim_id":"606502","title":"MEMBRANE-SPANNING 4-DOMAINS, SUBFAMILY A, MEMBER 7; MS4A7","url":"https://www.omim.org/entry/606502"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lung","ntpm":11.8}],"url":"https://www.proteinatlas.org/search/MS4A2"},"hgnc":{"alias_symbol":[],"prev_symbol":["FCER1B","IGER","APY"]},"alphafold":{"accession":"Q01362","domains":[{"cath_id":"-","chopping":"52-229","consensus_level":"high","plddt":86.0583,"start":52,"end":229}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q01362","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q01362-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q01362-F1-predicted_aligned_error_v6.png","plddt_mean":74.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MS4A2","jax_strain_url":"https://www.jax.org/strain/search?query=MS4A2"},"sequence":{"accession":"Q01362","fasta_url":"https://rest.uniprot.org/uniprotkb/Q01362.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q01362/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q01362"}},"corpus_meta":[{"pmid":"11447385","id":"PMC_11447385","title":"Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B.","date":"2001","source":"The Journal of allergy and clinical immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11447385","citation_count":55,"is_preprint":false},{"pmid":"10712341","id":"PMC_10712341","title":"A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population.","date":"2000","source":"American journal of respiratory and critical care medicine","url":"https://pubmed.ncbi.nlm.nih.gov/10712341","citation_count":52,"is_preprint":false},{"pmid":"16839402","id":"PMC_16839402","title":"A polymorphism of MS4A2 (- 109T > C) encoding the beta-chain of the high-affinity immunoglobulin E receptor (FcepsilonR1beta) is associated with a susceptibility to aspirin-intolerant asthma.","date":"2006","source":"Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16839402","citation_count":45,"is_preprint":false},{"pmid":"16839401","id":"PMC_16839401","title":"Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility.","date":"2006","source":"Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16839401","citation_count":35,"is_preprint":false},{"pmid":"24639354","id":"PMC_24639354","title":"Critical Roles for PU.1, GATA1, and GATA2 in the expression of human FcεRI on mast cells: PU.1 and GATA1 transactivate FCER1A, and GATA2 transactivates FCER1A and MS4A2.","date":"2014","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/24639354","citation_count":31,"is_preprint":false},{"pmid":"9746603","id":"PMC_9746603","title":"Expression of the virulence plasmid-carried apyrase gene (apy) of enteroinvasive Escherichia coli and Shigella flexneri is under the control of H-NS and the VirF and VirB regulatory cascade.","date":"1998","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/9746603","citation_count":31,"is_preprint":false},{"pmid":"2026316","id":"PMC_2026316","title":"Immunoreactivity to peptides belonging to the pancreatic polypeptide family (NPY, aPY, PP, PYY) and to glucagon-like peptide in the endocrine pancreas and anterior intestine of adult lampreys, Petromyzon marinus: an immunohistochemical study.","date":"1991","source":"General and comparative endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/2026316","citation_count":30,"is_preprint":false},{"pmid":"16452446","id":"PMC_16452446","title":"Apyrase, the product of the virulence plasmid-encoded phoN2 (apy) gene of Shigella flexneri, is necessary for proper unipolar IcsA localization and for efficient intercellular spread.","date":"2006","source":"Journal of 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2014,\n      \"finding\": \"GATA2 directly transactivates the MS4A2 (FcεRIβ) promoter via direct binding, as demonstrated by chromatin immunoprecipitation showing GATA2 binding to the MS4A2 promoter, luciferase reporter assay, and EMSA. Knockdown of GATA2 by siRNA in the human mast cell line LAD2 reduced MS4A2/FcεRIβ mRNA levels and suppressed IgE-mediated degranulation.\",\n      \"method\": \"siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assay, EMSA, flow cytometry for cell surface FcεRI\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (ChIP, EMSA, luciferase assay, siRNA knockdown with functional degranulation readout) in a single rigorous study\",\n      \"pmids\": [\"24639354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In mouse mast cells, GATA2 and PU.1 cooperatively but through distinct mechanisms activate Ms4a2 (FcεRIβ) gene expression. GATA2 exclusively binds the proximal −60-bp promoter region in a mast cell-specific manner, while both GATA2 and PU.1 share binding at a +10.4-kbp downstream enhancer region together with the chromatin looping factor LDB1. Deletion of the +10.4-kbp region by genome editing completely abolished Ms4a2 expression and cell surface FcεRI expression. PU.1 ablation reduced GATA2 binding at both regions, indicating PU.1 facilitates active chromatin structure for GATA2 access.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP), genome editing (deletion of +10.4-kbp region), siRNA knockdown, flow cytometry for FcεRI surface expression\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — genome editing with functional readout combined with ChIP and siRNA, multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"31501274\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Luciferase reporter assays showed that the FCER1B −109T allele is associated with higher promoter activity of MS4A2 compared to the −109C allele in both RBL-2H3 and A549 cell lines, indicating that this promoter polymorphism functionally affects MS4A2 transcriptional activity.\",\n      \"method\": \"Luciferase reporter assay in RBL-2H3 and A549 cell lines\",\n      \"journal\": \"Clinical and experimental allergy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay in two cell lines, single lab, single method type\",\n      \"pmids\": [\"16839402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The FCER1B −109T allele was associated with reduced FcεRIβ transcript levels measured in peripheral blood from human subjects, suggesting a promoter-dependent mechanism of transcriptional regulation of MS4A2.\",\n      \"method\": \"mRNA quantification correlated with promoter genotype in human subjects\",\n      \"journal\": \"International archives of allergy and immunology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, small sample (15 individuals), single method, no functional reconstitution\",\n      \"pmids\": [\"19218813\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Single-cell transcriptomic mapping localized MS4A2 expression to tumor-associated mast cells in lung adenocarcinoma, where MS4A2-high expression was associated with bidirectional chemokine regulation (suppressing CCL19/CCL21 while amplifying CCL20/CXCL8), suggesting a role in orchestrating leukocyte transendothelial migration.\",\n      \"method\": \"Single-cell RNA sequencing (scRNA-seq), bulk RNA-seq (TCGA/GTEx), immune infiltration analysis\",\n      \"journal\": \"International journal of surgery\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — computational/transcriptomic analysis only, no direct functional experiment on MS4A2 protein activity, single study\",\n      \"pmids\": [\"40607924\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MS4A2 (FcεRIβ) is the β-chain of the high-affinity IgE receptor (FcεRI) expressed on mast cells; its transcription is directly activated by GATA2 binding to the proximal promoter and to a critical +10.4-kbp downstream enhancer (together with PU.1 and LDB1 in a chromatin loop), with PU.1 facilitating active chromatin structure that enables GATA2 access, and together these factors drive FcεRI surface expression and IgE-mediated degranulation; additionally, a common promoter polymorphism (−109T/C) modulates MS4A2 promoter activity and FcεRIβ transcript levels.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MS4A2 encodes the FcεRIβ chain of the high-affinity IgE receptor expressed on mast cells, where its expression is required for cell-surface FcεRI display and IgE-mediated degranulation [#0]. Transcription is driven by GATA2, which binds the proximal MS4A2 promoter and directly transactivates the gene; GATA2 knockdown lowers FcεRIβ mRNA and suppresses IgE-triggered degranulation [#0]. GATA2 acts together with PU.1 through distinct but cooperative mechanisms: GATA2 binds the proximal −60-bp promoter in a mast cell-specific manner, while both GATA2 and PU.1 occupy a +10.4-kbp downstream enhancer alongside the chromatin-looping factor LDB1, with PU.1 establishing active chromatin that enables GATA2 access; deletion of the +10.4-kbp enhancer abolishes both Ms4a2 expression and surface FcεRI [#1]. A common −109T/C promoter polymorphism modulates MS4A2 promoter activity, with the −109T allele conferring higher transcriptional activity [#2]. Beyond this transcriptional control of FcεRIβ in mast cells, the protein's own signaling biochemistry is not characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Whether sequence variation in the MS4A2 promoter functionally alters its transcription was unknown; this established that the −109T allele drives higher promoter activity than the −109C allele.\",\n      \"evidence\": \"Luciferase reporter assays comparing alleles in RBL-2H3 and A549 cell lines\",\n      \"pmids\": [\"16839402\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single method type in one lab\", \"No endogenous chromatin or transcription factor binding context for the variant\", \"Functional consequence for FcεRI surface expression not tested\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To test whether the promoter genotype predicts transcript abundance in vivo, this correlated the −109T allele with reduced FcεRIβ mRNA in human peripheral blood.\",\n      \"evidence\": \"mRNA quantification correlated with promoter genotype in human subjects\",\n      \"pmids\": [\"19218813\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single small cohort (15 individuals), no functional reconstitution\", \"Direction relative to reporter findings not mechanistically reconciled\", \"No causal manipulation\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The trans-acting factor controlling MS4A2 was unresolved; this identified GATA2 as a direct transcriptional activator whose loss impairs FcεRI-driven mast cell function.\",\n      \"evidence\": \"ChIP, EMSA, luciferase reporter, and siRNA knockdown with degranulation readout in human LAD2 mast cells\",\n      \"pmids\": [\"24639354\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Cooperating factors and distal regulatory elements not yet defined\", \"Mechanism of mast cell-specific promoter selection unaddressed\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"How GATA2 achieves mast cell-specific, locus-wide activation was unknown; this resolved a two-element architecture in which GATA2 binds the proximal promoter while GATA2/PU.1/LDB1 cooperate at an essential +10.4-kbp enhancer.\",\n      \"evidence\": \"ChIP, genome-editing deletion of the +10.4-kbp enhancer, and siRNA in mouse mast cells with FcεRI surface readout\",\n      \"pmids\": [\"31501274\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Direct LDB1-mediated loop topology not structurally resolved\", \"Human enhancer equivalence to mouse +10.4-kbp element not established\", \"Integration with −109 promoter variant unexplored\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether MS4A2 marks functionally distinct mast cell states in disease was unaddressed; this localized MS4A2-high tumor-associated mast cells and correlated them with bidirectional chemokine regulation in lung adenocarcinoma.\",\n      \"evidence\": \"Single-cell and bulk RNA-seq with immune infiltration analysis\",\n      \"pmids\": [\"40607924\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Computational/transcriptomic only, no functional test of MS4A2 protein activity\", \"Causal role of MS4A2 in chemokine output not demonstrated\", \"Single study\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The signaling biochemistry of the FcεRIβ protein itself — its partners, membrane assembly, and contribution to receptor signal amplification — remains uncharacterized in this corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct protein-level interaction or signaling data in the timeline\", \"No structural model of the receptor complex\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"FcεRI (high-affinity IgE receptor)\"],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}