{"gene":"LAMTOR2","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2014,"finding":"Late endosomes carrying the p14-MP1 (LAMTOR2/3) complex move to the cell periphery along microtubules in a kinesin1- and Arl8b-dependent manner, where they target focal adhesions (FAs) to trigger IQGAP1 disassociation from FAs, thereby regulating FA turnover required for cell migration.","method":"Genetically modified p14-deficient mouse fibroblasts, Arl8b siRNA depletion, live imaging, colocalization studies","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic loss-of-function (KO + KD) with defined cellular phenotype (FA turnover, IQGAP1 release, migration), multiple orthogonal methods, replicated across two genetic conditions","pmids":["24841562"],"is_preprint":false},{"year":2013,"finding":"LAMTOR2/p14 deficiency disrupts the LAMTOR complex, leading to malfunction of both ERK and mTOR signaling pathways, which impairs proliferation and increases apoptosis of Langerhans cells, resulting in near-complete loss of Langerhans cells in the epidermis.","method":"Conditional knockout mouse model (CD11c-specific p14 deletion), in vivo LC repopulation analysis, signaling pathway analysis","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean in vivo conditional KO with defined molecular pathway (LAMTOR complex disruption → ERK/mTOR loss) and specific cellular phenotype (LC loss), multiple readouts","pmids":["24092934"],"is_preprint":false},{"year":2014,"finding":"LAMTOR2 conditional ablation in dendritic cells causes accumulation of Flt3 receptor on the cell surface, leading to increased AKT/mTOR downstream signaling and massive expansion of conventional and plasmacytoid DCs; this is reversible by inhibiting Flt3 or mTOR in vivo.","method":"Conditional knockout mouse model (DC-specific LAMTOR2 deletion), in vivo Flt3 and mTOR inhibitor treatment, surface receptor quantification","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo conditional KO with defined pathway placement (Flt3 accumulation → AKT/mTOR), pharmacological rescue experiment, multiple orthogonal approaches","pmids":["25336251"],"is_preprint":false},{"year":2014,"finding":"LAMTOR2 deficiency in LCs interferes with the TGFβ1 pathway by lowering TGFβ receptor II expression and surface binding of TGFβ1 on BMDCs, impairing LC homeostasis and reducing contact hypersensitivity responses.","method":"Langerin-specific conditional KO mouse, BMDC analysis, TGFβRII surface staining, contact hypersensitivity assays","journal":"The Journal of investigative dermatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined molecular pathway (TGFβRII reduction), single lab with two orthogonal readouts (receptor expression + ligand binding)","pmids":["25078666"],"is_preprint":false},{"year":2015,"finding":"LAMTOR2-deficient mouse embryonic fibroblasts show reduced numbers of recycling tubules from multivesicular bodies (MVBs), accumulation of mature MVB and (autophago)lysosomes, and impaired transferrin receptor recycling; these morphological changes are similarly induced in control cells by mTOR inactivation, placing LAMTOR2 upstream of mTOR in endo/lysosomal tubule formation.","method":"Quantitative immunoelectron microscopy of cryo-fixed LAMTOR2-KO MEFs, mTOR inhibitor treatment, transferrin receptor trafficking assays","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM ultrastructural quantification with genetic KO and pharmacological epistasis (mTOR inhibitor phenocopies KO), single lab with multiple orthogonal ultrastructural and trafficking methods","pmids":["25677580"],"is_preprint":false},{"year":2014,"finding":"LAMTOR2 knockdown in PC12 cells augments NGF-dependent MAPK activation and neurite outgrowth by causing faster release of the TrkA/MAPK signaling module from early endosomes to the nucleus; ectopic expression of siRNA-resistant LAMTOR2 reverses this phenotype, confirming specificity.","method":"siRNA knockdown and rescue with siRNA-resistant LAMTOR2 ortholog in PC12 cells, NGF stimulation, MAPK activation kinetics, TrkA colocalization with early endosomes by imaging","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KD + rescue experiment (siRNA-resistant ortholog), live imaging of TrkA trafficking, MAPK activation kinetics, single lab with multiple orthogonal approaches","pmids":["24752675"],"is_preprint":false},{"year":2019,"finding":"LAMTOR2 and LAMTOR1 form a complex required for xenophagy: LAMTOR1 localizes to bacterium-containing endosomes and recruits LAMTOR2 to damaged endosomes; LAMTOR2 then interacts with autophagy receptors NBR1, TAX1BP1, and p62, and is required for TAX1BP1 recruitment to pathogen-containing autophagosomes and subsequent autolysosome formation during Group A Streptococcus and Salmonella infection.","method":"Co-immunoprecipitation (LAMTOR2 with NBR1/TAX1BP1/p62), LAMTOR2 KO cells, fluorescence localization, TAX1BP1 KO bacterial degradation assay","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for direct interaction, genetic KO with defined xenophagy phenotype (autolysosome formation), single lab with multiple methods","pmids":["30428163"],"is_preprint":false},{"year":2019,"finding":"LAMTOR2 is critical for B-cell development: conditional deletion (mb1-Cre) causes complete developmental arrest at the pre-B1 stage; deletion at a later stage (Cd19-Cre) reveals LAMTOR2 is required for BCR internalization and endosomal trafficking, with loss causing aberrant BCR signaling.","method":"Conditional KO mice (mb1-Cre and Cd19-Cre), BCR internalization assays, endosomal trafficking analysis, signaling readouts","journal":"Frontiers in immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — two independent conditional KO models, defined molecular mechanism (BCR internalization and endosomal trafficking defect), multiple developmental stage readouts","pmids":["30936881"],"is_preprint":false},{"year":2020,"finding":"SCFAs acting through GPR43 upregulate LAMTOR2 in macrophages; LAMTOR2 facilitates phagosome-lysosome fusion and ERK phosphorylation, enhancing bacterial clearance of K. pneumoniae; conditional macrophage-specific Lamtor2 ablation abolishes this SCFA-dependent antimicrobial activity.","method":"Macrophage-specific conditional Lamtor2 KO mice, SCFA/GPR43 stimulation, phagosome-lysosome fusion assay, ERK phosphorylation assay","journal":"mSystems","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional macrophage KO with defined phenotype (phagosome-lysosome fusion, ERK phosphorylation), single lab with multiple mechanistic readouts","pmids":["33144310"],"is_preprint":false},{"year":2023,"finding":"VSIG2 simultaneously binds to both LAMTOR2 and mTOR (identified by mass spectrometry and co-immunoprecipitation), acting as a scaffold that stabilizes the LAMTOR2–mTOR interaction and enhances phosphorylation-mediated mTOR activation and downstream signaling in pancreatic ductal adenocarcinoma cells.","method":"Mass spectrometry, co-immunoprecipitation, immunofluorescence colocalization, VSIG2 overexpression/knockdown with mTOR pathway readouts","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and MS for interaction, functional overexpression/KD with mTOR phosphorylation readouts, single lab","pmids":["37626304"],"is_preprint":false},{"year":2025,"finding":"BCLAF1 interacts with LAMTOR2 (identified by immunoprecipitation and protein mass spectrometry), and LAMTOR2 regulates the nuclear translocation of BCLAF1 in chondrocytes, thereby influencing cartilage degradation pathways.","method":"Immunoprecipitation, protein mass spectrometry, BCLAF1 nuclear translocation assay in chondrocytes","journal":"International journal of biological sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS identification of interaction, nuclear translocation assay described in abstract without detailed mechanistic follow-up, single lab","pmids":["39990659"],"is_preprint":false}],"current_model":"LAMTOR2 (p14) is a late endosomal/lysosomal scaffold protein that is part of the LAMTOR/Ragulator complex, where it coordinates ERK/MAPK and mTOR signaling, regulates endosomal biogenesis (MVB recycling tubule formation and phagosome-lysosome fusion), controls surface receptor trafficking (EGFR, TrkA, BCR, Flt3), recruits autophagy receptors (TAX1BP1) for xenophagy, and transports signaling cargo along microtubules (via kinesin1/Arl8b) to focal adhesions to regulate cell migration—collectively positioning LAMTOR2 as a multifunctional endosomal hub that integrates intracellular trafficking with MAPK/mTOR signal transduction in diverse immune and non-immune cell types."},"narrative":{"mechanistic_narrative":"LAMTOR2 (p14) is a late endosomal/lysosomal scaffold subunit of the LAMTOR/Ragulator complex that integrates ERK/MAPK and mTOR signaling with intracellular membrane trafficking, and its loss disrupts both pathways with broad consequences for immune cell development and homeostasis [PMID:24092934]. As a component of the p14–MP1 (LAMTOR2/3) module, it positions late endosomes for kinesin1- and Arl8b-dependent microtubule transport to focal adhesions, where it drives IQGAP1 release and focal adhesion turnover required for cell migration [PMID:24841562], and it acts upstream of mTOR to support multivesicular body recycling tubule formation and transferrin receptor recycling [PMID:25677580]. LAMTOR2 governs the trafficking and signaling output of multiple surface receptors: it restrains Flt3 surface accumulation and downstream AKT/mTOR-driven dendritic cell expansion [PMID:25336251], controls BCR internalization and endosomal trafficking during B-cell development [PMID:30936881], modulates TrkA/MAPK signaling-module release from early endosomes during NGF-induced neurite outgrowth [PMID:24752675], and sustains TGFβ receptor II expression in Langerhans cell homeostasis [PMID:25078666]. In macrophages it promotes phagosome-lysosome fusion and ERK phosphorylation for bacterial clearance [PMID:33144310], and together with LAMTOR1 it is recruited to damaged pathogen-containing endosomes where it binds the autophagy receptors NBR1, TAX1BP1, and p62 to drive xenophagic autolysosome formation [PMID:30428163]. Its scaffolding role is further tuned by partner proteins, with VSIG2 stabilizing the LAMTOR2–mTOR interaction to enhance mTOR activation [PMID:37626304].","teleology":[{"year":2013,"claim":"Established that LAMTOR2 is the linchpin holding the LAMTOR complex together, so that its loss simultaneously cripples both ERK and mTOR signaling and a defined immune cell population.","evidence":"CD11c-specific conditional knockout mouse with in vivo Langerhans cell repopulation and signaling analysis","pmids":["24092934"],"confidence":"High","gaps":["Does not resolve which downstream effectors of ERK vs mTOR drive the proliferation/apoptosis phenotype","Mechanism of complex disassembly upon p14 loss not structurally defined"]},{"year":2014,"claim":"Showed LAMTOR2 couples endosome positioning to cytoskeletal motors and adhesion dynamics, linking the complex to cell migration beyond canonical signaling.","evidence":"p14-deficient mouse fibroblasts with Arl8b siRNA depletion, live imaging and colocalization at focal adhesions","pmids":["24841562"],"confidence":"High","gaps":["Direct biochemical link between LAMTOR2 cargo and IQGAP1 release unresolved","Whether ERK/mTOR signaling is required for the FA-turnover function not separated"]},{"year":2014,"claim":"Demonstrated that LAMTOR2 restrains surface receptor abundance, with Flt3 accumulation driving AKT/mTOR-dependent DC expansion that is pharmacologically reversible.","evidence":"DC-specific conditional KO with in vivo Flt3 and mTOR inhibitor rescue and surface receptor quantification","pmids":["25336251"],"confidence":"High","gaps":["Trafficking step at which Flt3 is normally degraded not pinpointed","Whether other receptors are similarly retained at the surface unaddressed here"]},{"year":2014,"claim":"Extended LAMTOR2's receptor-trafficking role to TGFβ signaling and to TrkA/MAPK kinetics, framing it as a brake on signaling-module release from endosomes.","evidence":"Langerin-specific conditional KO with TGFβRII surface staining (TGFβ); PC12 siRNA knockdown plus siRNA-resistant rescue with NGF-induced MAPK kinetics and TrkA endosome imaging (TrkA)","pmids":["25078666","24752675"],"confidence":"Medium","gaps":["Mechanism by which LAMTOR2 controls TGFβRII expression vs trafficking not distinguished","How LAMTOR2 retards TrkA/MAPK endosome-to-nucleus transit biochemically undefined"]},{"year":2015,"claim":"Placed LAMTOR2 upstream of mTOR in endo/lysosomal membrane remodeling by showing mTOR inhibition phenocopies the KO ultrastructural defect.","evidence":"Quantitative immunoelectron microscopy of LAMTOR2-KO MEFs with mTOR-inhibitor epistasis and transferrin receptor recycling assays","pmids":["25677580"],"confidence":"High","gaps":["Molecular machinery of recycling-tubule scission downstream of mTOR not identified","Generality of the MVB phenotype beyond fibroblasts untested"]},{"year":2019,"claim":"Identified LAMTOR2 as a receptor for selective autophagy, recruiting xenophagy adaptors to damaged pathogen-containing endosomes.","evidence":"Co-IP of LAMTOR2 with NBR1/TAX1BP1/p62, LAMTOR2 KO cells and TAX1BP1 KO bacterial degradation assays during GAS/Salmonella infection","pmids":["30428163"],"confidence":"Medium","gaps":["Direct vs indirect nature of LAMTOR2–TAX1BP1 binding not established","Whether autophagy-receptor recruitment depends on the canonical Ragulator/mTOR function unclear"]},{"year":2019,"claim":"Defined a stage-specific requirement for LAMTOR2 in B-cell development driven by its control of BCR internalization and endosomal trafficking.","evidence":"Two independent conditional KO models (mb1-Cre, Cd19-Cre) with BCR internalization and endosomal trafficking assays","pmids":["30936881"],"confidence":"High","gaps":["Whether the pre-B1 arrest reflects signaling vs trafficking failure not separated","Effector linking BCR trafficking defect to aberrant signaling unidentified"]},{"year":2020,"claim":"Connected extracellular SCFA/GPR43 signaling to LAMTOR2-dependent phagosome-lysosome fusion and ERK activation in antimicrobial macrophage function.","evidence":"Macrophage-specific conditional Lamtor2 KO with SCFA/GPR43 stimulation, phagosome-lysosome fusion and ERK phosphorylation assays","pmids":["33144310"],"confidence":"Medium","gaps":["Transcriptional mechanism by which GPR43 upregulates LAMTOR2 not detailed","Whether ERK and fusion functions are mechanistically coupled unaddressed"]},{"year":2023,"claim":"Showed LAMTOR2's mTOR-activating scaffold function can be amplified by a partner, VSIG2, that bridges LAMTOR2 and mTOR.","evidence":"Mass spectrometry and reciprocal co-IP with VSIG2 overexpression/knockdown and mTOR phosphorylation readouts in PDAC cells","pmids":["37626304"],"confidence":"Medium","gaps":["Structural basis of the trimeric VSIG2–LAMTOR2–mTOR assembly unknown","Single cancer-cell context; generality untested"]},{"year":2025,"claim":"Proposed a nuclear-signaling arm in which LAMTOR2 controls BCLAF1 nuclear translocation in chondrocytes affecting cartilage degradation.","evidence":"Immunoprecipitation/mass spectrometry and BCLAF1 nuclear translocation assay in chondrocytes","pmids":["39990659"],"confidence":"Low","gaps":["Single Co-IP/MS identification without reciprocal validation","Mechanism by which an endosomal scaffold controls nuclear translocation undefined","Downstream cartilage-degradation pathway not mechanistically traced"]},{"year":null,"claim":"How LAMTOR2 partitions its scaffold time between Ragulator/mTOR signaling, receptor trafficking, autophagy-receptor recruitment, and motor-driven endosome positioning—and what determines context-specific output—remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of LAMTOR2 engaging its diverse partners across functions","Rules governing which cargo/pathway LAMTOR2 serves in a given cell type unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,6,9]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,2,4]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,5,6]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[4,8]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2,5,8]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,4,7]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[6]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,2,7,8]}],"complexes":["LAMTOR/Ragulator complex","p14-MP1 (LAMTOR2/3) complex"],"partners":["LAMTOR3","LAMTOR1","TAX1BP1","NBR1","SQSTM1","VSIG2","MTOR","BCLAF1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y2Q5","full_name":"Ragulator complex protein LAMTOR2","aliases":["Endosomal adaptor protein p14","Late endosomal/lysosomal Mp1-interacting protein","Late endosomal/lysosomal adaptor and MAPK and MTOR activator 2","Mitogen-activated protein-binding protein-interacting protein","MAPBP-interacting protein","Roadblock domain-containing protein 3"],"length_aa":125,"mass_kda":13.5,"function":"As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:20381137, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:30181260). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:22980980, PubMed:29107538, PubMed:29123114, PubMed:29158492). Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2 (By similarity)","subcellular_location":"Late endosome membrane; Lysosome membrane","url":"https://www.uniprot.org/uniprotkb/Q9Y2Q5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/LAMTOR2","classification":"Common Essential","n_dependent_lines":784,"n_total_lines":1208,"dependency_fraction":0.6490066225165563},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000116586","cell_line_id":"CID001005","localizations":[{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"LAMTOR5","stoichiometry":10.0},{"gene":"LAMTOR1","stoichiometry":10.0},{"gene":"LAMTOR3","stoichiometry":10.0},{"gene":"PIP4P1","stoichiometry":4.0},{"gene":"LAMP1","stoichiometry":0.2},{"gene":"BLOC1S2","stoichiometry":0.2},{"gene":"SCAMP3","stoichiometry":0.2},{"gene":"RAB2A","stoichiometry":0.2},{"gene":"RAB7A","stoichiometry":0.2},{"gene":"SLC18B1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001005","total_profiled":1310},"omim":[{"mim_id":"621247","title":"CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 7; CPSF7","url":"https://www.omim.org/entry/621247"},{"mim_id":"618834","title":"LATE ENDOSOMAL/LYSOSOMAL ADAPTOR, MAPK AND MTOR ACTIVATOR 4; LAMTOR4","url":"https://www.omim.org/entry/618834"},{"mim_id":"610798","title":"IMMUNODEFICIENCY DUE TO DEFECT IN MAPBP-INTERACTING PROTEIN","url":"https://www.omim.org/entry/610798"},{"mim_id":"610389","title":"LATE ENDOSOMAL/LYSOSOMAL ADAPTOR, MAPK AND MTOR ACTIVATOR 2; LAMTOR2","url":"https://www.omim.org/entry/610389"},{"mim_id":"608521","title":"LATE ENDOSOMAL/LYSOSOMAL ADAPTOR, MAPK AND MTOR ACTIVATOR 5; LAMTOR5","url":"https://www.omim.org/entry/608521"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/LAMTOR2"},"hgnc":{"alias_symbol":["MAPBPIP","MAPKSP1AP","p14","ENDAP","Ragulator2"],"prev_symbol":["ROBLD3"]},"alphafold":{"accession":"Q9Y2Q5","domains":[{"cath_id":"3.30.450.30","chopping":"3-120","consensus_level":"high","plddt":93.2786,"start":3,"end":120}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2Q5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2Q5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2Q5-F1-predicted_aligned_error_v6.png","plddt_mean":91.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LAMTOR2","jax_strain_url":"https://www.jax.org/strain/search?query=LAMTOR2"},"sequence":{"accession":"Q9Y2Q5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y2Q5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y2Q5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2Q5"}},"corpus_meta":[{"pmid":"24841562","id":"PMC_24841562","title":"The late endosomal p14-MP1 (LAMTOR2/3) complex regulates focal adhesion dynamics during cell migration.","date":"2014","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/24841562","citation_count":76,"is_preprint":false},{"pmid":"33144310","id":"PMC_33144310","title":"Microbiota-Derived Short-Chain Fatty Acids Promote LAMTOR2-Mediated Immune Responses in Macrophages.","date":"2020","source":"mSystems","url":"https://pubmed.ncbi.nlm.nih.gov/33144310","citation_count":70,"is_preprint":false},{"pmid":"24092934","id":"PMC_24092934","title":"The late endosomal adaptor molecule p14 (LAMTOR2) represents a novel regulator of Langerhans cell homeostasis.","date":"2013","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/24092934","citation_count":46,"is_preprint":false},{"pmid":"25336251","id":"PMC_25336251","title":"LAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25336251","citation_count":40,"is_preprint":false},{"pmid":"25677580","id":"PMC_25677580","title":"Ultrastructural Morphometry Points to a New Role for LAMTOR2 in Regulating the Endo/Lysosomal System.","date":"2015","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/25677580","citation_count":30,"is_preprint":false},{"pmid":"25078666","id":"PMC_25078666","title":"The late endosomal adaptor molecule p14 (LAMTOR2) regulates TGFβ1-mediated homeostasis of Langerhans cells.","date":"2014","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/25078666","citation_count":24,"is_preprint":false},{"pmid":"30428163","id":"PMC_30428163","title":"LAMTOR2/LAMTOR1 complex is required for TAX1BP1-mediated xenophagy.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30428163","citation_count":21,"is_preprint":false},{"pmid":"37626304","id":"PMC_37626304","title":"VSIG2 promotes malignant progression of pancreatic ductal adenocarcinoma by enhancing LAMTOR2-mediated mTOR activation.","date":"2023","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/37626304","citation_count":13,"is_preprint":false},{"pmid":"30936881","id":"PMC_30936881","title":"LAMTOR2 (p14) Controls B Cell Differentiation by Orchestrating Endosomal BCR Trafficking.","date":"2019","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30936881","citation_count":9,"is_preprint":false},{"pmid":"24752675","id":"PMC_24752675","title":"LAMTOR2-mediated modulation of NGF/MAPK activation kinetics during differentiation of PC12 cells.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24752675","citation_count":9,"is_preprint":false},{"pmid":"23341997","id":"PMC_23341997","title":"Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23341997","citation_count":9,"is_preprint":false},{"pmid":"39990659","id":"PMC_39990659","title":"BCLAF1 Regulates Osteoarthritic Cartilage Degradation Through Interaction with LAMTOR2.","date":"2025","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39990659","citation_count":2,"is_preprint":false},{"pmid":"35732604","id":"PMC_35732604","title":"[LAMTOR2 deficiency exacerbates Klebsiella pneumoniae-induced liver sepsis in mice].","date":"2022","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35732604","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8808,"output_tokens":2911,"usd":0.035044,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10394,"output_tokens":3801,"usd":0.073497,"stage2_stop_reason":"end_turn"},"total_usd":0.108541,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Late endosomes carrying the p14-MP1 (LAMTOR2/3) complex move to the cell periphery along microtubules in a kinesin1- and Arl8b-dependent manner, where they target focal adhesions (FAs) to trigger IQGAP1 disassociation from FAs, thereby regulating FA turnover required for cell migration.\",\n      \"method\": \"Genetically modified p14-deficient mouse fibroblasts, Arl8b siRNA depletion, live imaging, colocalization studies\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic loss-of-function (KO + KD) with defined cellular phenotype (FA turnover, IQGAP1 release, migration), multiple orthogonal methods, replicated across two genetic conditions\",\n      \"pmids\": [\"24841562\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"LAMTOR2/p14 deficiency disrupts the LAMTOR complex, leading to malfunction of both ERK and mTOR signaling pathways, which impairs proliferation and increases apoptosis of Langerhans cells, resulting in near-complete loss of Langerhans cells in the epidermis.\",\n      \"method\": \"Conditional knockout mouse model (CD11c-specific p14 deletion), in vivo LC repopulation analysis, signaling pathway analysis\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean in vivo conditional KO with defined molecular pathway (LAMTOR complex disruption → ERK/mTOR loss) and specific cellular phenotype (LC loss), multiple readouts\",\n      \"pmids\": [\"24092934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"LAMTOR2 conditional ablation in dendritic cells causes accumulation of Flt3 receptor on the cell surface, leading to increased AKT/mTOR downstream signaling and massive expansion of conventional and plasmacytoid DCs; this is reversible by inhibiting Flt3 or mTOR in vivo.\",\n      \"method\": \"Conditional knockout mouse model (DC-specific LAMTOR2 deletion), in vivo Flt3 and mTOR inhibitor treatment, surface receptor quantification\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo conditional KO with defined pathway placement (Flt3 accumulation → AKT/mTOR), pharmacological rescue experiment, multiple orthogonal approaches\",\n      \"pmids\": [\"25336251\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"LAMTOR2 deficiency in LCs interferes with the TGFβ1 pathway by lowering TGFβ receptor II expression and surface binding of TGFβ1 on BMDCs, impairing LC homeostasis and reducing contact hypersensitivity responses.\",\n      \"method\": \"Langerin-specific conditional KO mouse, BMDC analysis, TGFβRII surface staining, contact hypersensitivity assays\",\n      \"journal\": \"The Journal of investigative dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined molecular pathway (TGFβRII reduction), single lab with two orthogonal readouts (receptor expression + ligand binding)\",\n      \"pmids\": [\"25078666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"LAMTOR2-deficient mouse embryonic fibroblasts show reduced numbers of recycling tubules from multivesicular bodies (MVBs), accumulation of mature MVB and (autophago)lysosomes, and impaired transferrin receptor recycling; these morphological changes are similarly induced in control cells by mTOR inactivation, placing LAMTOR2 upstream of mTOR in endo/lysosomal tubule formation.\",\n      \"method\": \"Quantitative immunoelectron microscopy of cryo-fixed LAMTOR2-KO MEFs, mTOR inhibitor treatment, transferrin receptor trafficking assays\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM ultrastructural quantification with genetic KO and pharmacological epistasis (mTOR inhibitor phenocopies KO), single lab with multiple orthogonal ultrastructural and trafficking methods\",\n      \"pmids\": [\"25677580\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"LAMTOR2 knockdown in PC12 cells augments NGF-dependent MAPK activation and neurite outgrowth by causing faster release of the TrkA/MAPK signaling module from early endosomes to the nucleus; ectopic expression of siRNA-resistant LAMTOR2 reverses this phenotype, confirming specificity.\",\n      \"method\": \"siRNA knockdown and rescue with siRNA-resistant LAMTOR2 ortholog in PC12 cells, NGF stimulation, MAPK activation kinetics, TrkA colocalization with early endosomes by imaging\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KD + rescue experiment (siRNA-resistant ortholog), live imaging of TrkA trafficking, MAPK activation kinetics, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"24752675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"LAMTOR2 and LAMTOR1 form a complex required for xenophagy: LAMTOR1 localizes to bacterium-containing endosomes and recruits LAMTOR2 to damaged endosomes; LAMTOR2 then interacts with autophagy receptors NBR1, TAX1BP1, and p62, and is required for TAX1BP1 recruitment to pathogen-containing autophagosomes and subsequent autolysosome formation during Group A Streptococcus and Salmonella infection.\",\n      \"method\": \"Co-immunoprecipitation (LAMTOR2 with NBR1/TAX1BP1/p62), LAMTOR2 KO cells, fluorescence localization, TAX1BP1 KO bacterial degradation assay\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for direct interaction, genetic KO with defined xenophagy phenotype (autolysosome formation), single lab with multiple methods\",\n      \"pmids\": [\"30428163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"LAMTOR2 is critical for B-cell development: conditional deletion (mb1-Cre) causes complete developmental arrest at the pre-B1 stage; deletion at a later stage (Cd19-Cre) reveals LAMTOR2 is required for BCR internalization and endosomal trafficking, with loss causing aberrant BCR signaling.\",\n      \"method\": \"Conditional KO mice (mb1-Cre and Cd19-Cre), BCR internalization assays, endosomal trafficking analysis, signaling readouts\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two independent conditional KO models, defined molecular mechanism (BCR internalization and endosomal trafficking defect), multiple developmental stage readouts\",\n      \"pmids\": [\"30936881\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SCFAs acting through GPR43 upregulate LAMTOR2 in macrophages; LAMTOR2 facilitates phagosome-lysosome fusion and ERK phosphorylation, enhancing bacterial clearance of K. pneumoniae; conditional macrophage-specific Lamtor2 ablation abolishes this SCFA-dependent antimicrobial activity.\",\n      \"method\": \"Macrophage-specific conditional Lamtor2 KO mice, SCFA/GPR43 stimulation, phagosome-lysosome fusion assay, ERK phosphorylation assay\",\n      \"journal\": \"mSystems\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional macrophage KO with defined phenotype (phagosome-lysosome fusion, ERK phosphorylation), single lab with multiple mechanistic readouts\",\n      \"pmids\": [\"33144310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"VSIG2 simultaneously binds to both LAMTOR2 and mTOR (identified by mass spectrometry and co-immunoprecipitation), acting as a scaffold that stabilizes the LAMTOR2–mTOR interaction and enhances phosphorylation-mediated mTOR activation and downstream signaling in pancreatic ductal adenocarcinoma cells.\",\n      \"method\": \"Mass spectrometry, co-immunoprecipitation, immunofluorescence colocalization, VSIG2 overexpression/knockdown with mTOR pathway readouts\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and MS for interaction, functional overexpression/KD with mTOR phosphorylation readouts, single lab\",\n      \"pmids\": [\"37626304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"BCLAF1 interacts with LAMTOR2 (identified by immunoprecipitation and protein mass spectrometry), and LAMTOR2 regulates the nuclear translocation of BCLAF1 in chondrocytes, thereby influencing cartilage degradation pathways.\",\n      \"method\": \"Immunoprecipitation, protein mass spectrometry, BCLAF1 nuclear translocation assay in chondrocytes\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS identification of interaction, nuclear translocation assay described in abstract without detailed mechanistic follow-up, single lab\",\n      \"pmids\": [\"39990659\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LAMTOR2 (p14) is a late endosomal/lysosomal scaffold protein that is part of the LAMTOR/Ragulator complex, where it coordinates ERK/MAPK and mTOR signaling, regulates endosomal biogenesis (MVB recycling tubule formation and phagosome-lysosome fusion), controls surface receptor trafficking (EGFR, TrkA, BCR, Flt3), recruits autophagy receptors (TAX1BP1) for xenophagy, and transports signaling cargo along microtubules (via kinesin1/Arl8b) to focal adhesions to regulate cell migration—collectively positioning LAMTOR2 as a multifunctional endosomal hub that integrates intracellular trafficking with MAPK/mTOR signal transduction in diverse immune and non-immune cell types.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LAMTOR2 (p14) is a late endosomal/lysosomal scaffold subunit of the LAMTOR/Ragulator complex that integrates ERK/MAPK and mTOR signaling with intracellular membrane trafficking, and its loss disrupts both pathways with broad consequences for immune cell development and homeostasis [#1]. As a component of the p14–MP1 (LAMTOR2/3) module, it positions late endosomes for kinesin1- and Arl8b-dependent microtubule transport to focal adhesions, where it drives IQGAP1 release and focal adhesion turnover required for cell migration [#0], and it acts upstream of mTOR to support multivesicular body recycling tubule formation and transferrin receptor recycling [#4]. LAMTOR2 governs the trafficking and signaling output of multiple surface receptors: it restrains Flt3 surface accumulation and downstream AKT/mTOR-driven dendritic cell expansion [#2], controls BCR internalization and endosomal trafficking during B-cell development [#7], modulates TrkA/MAPK signaling-module release from early endosomes during NGF-induced neurite outgrowth [#5], and sustains TGFβ receptor II expression in Langerhans cell homeostasis [#3]. In macrophages it promotes phagosome-lysosome fusion and ERK phosphorylation for bacterial clearance [#8], and together with LAMTOR1 it is recruited to damaged pathogen-containing endosomes where it binds the autophagy receptors NBR1, TAX1BP1, and p62 to drive xenophagic autolysosome formation [#6]. Its scaffolding role is further tuned by partner proteins, with VSIG2 stabilizing the LAMTOR2–mTOR interaction to enhance mTOR activation [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that LAMTOR2 is the linchpin holding the LAMTOR complex together, so that its loss simultaneously cripples both ERK and mTOR signaling and a defined immune cell population.\",\n      \"evidence\": \"CD11c-specific conditional knockout mouse with in vivo Langerhans cell repopulation and signaling analysis\",\n      \"pmids\": [\"24092934\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not resolve which downstream effectors of ERK vs mTOR drive the proliferation/apoptosis phenotype\", \"Mechanism of complex disassembly upon p14 loss not structurally defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed LAMTOR2 couples endosome positioning to cytoskeletal motors and adhesion dynamics, linking the complex to cell migration beyond canonical signaling.\",\n      \"evidence\": \"p14-deficient mouse fibroblasts with Arl8b siRNA depletion, live imaging and colocalization at focal adhesions\",\n      \"pmids\": [\"24841562\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical link between LAMTOR2 cargo and IQGAP1 release unresolved\", \"Whether ERK/mTOR signaling is required for the FA-turnover function not separated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated that LAMTOR2 restrains surface receptor abundance, with Flt3 accumulation driving AKT/mTOR-dependent DC expansion that is pharmacologically reversible.\",\n      \"evidence\": \"DC-specific conditional KO with in vivo Flt3 and mTOR inhibitor rescue and surface receptor quantification\",\n      \"pmids\": [\"25336251\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trafficking step at which Flt3 is normally degraded not pinpointed\", \"Whether other receptors are similarly retained at the surface unaddressed here\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Extended LAMTOR2's receptor-trafficking role to TGFβ signaling and to TrkA/MAPK kinetics, framing it as a brake on signaling-module release from endosomes.\",\n      \"evidence\": \"Langerin-specific conditional KO with TGFβRII surface staining (TGFβ); PC12 siRNA knockdown plus siRNA-resistant rescue with NGF-induced MAPK kinetics and TrkA endosome imaging (TrkA)\",\n      \"pmids\": [\"25078666\", \"24752675\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which LAMTOR2 controls TGFβRII expression vs trafficking not distinguished\", \"How LAMTOR2 retards TrkA/MAPK endosome-to-nucleus transit biochemically undefined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed LAMTOR2 upstream of mTOR in endo/lysosomal membrane remodeling by showing mTOR inhibition phenocopies the KO ultrastructural defect.\",\n      \"evidence\": \"Quantitative immunoelectron microscopy of LAMTOR2-KO MEFs with mTOR-inhibitor epistasis and transferrin receptor recycling assays\",\n      \"pmids\": [\"25677580\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular machinery of recycling-tubule scission downstream of mTOR not identified\", \"Generality of the MVB phenotype beyond fibroblasts untested\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified LAMTOR2 as a receptor for selective autophagy, recruiting xenophagy adaptors to damaged pathogen-containing endosomes.\",\n      \"evidence\": \"Co-IP of LAMTOR2 with NBR1/TAX1BP1/p62, LAMTOR2 KO cells and TAX1BP1 KO bacterial degradation assays during GAS/Salmonella infection\",\n      \"pmids\": [\"30428163\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect nature of LAMTOR2–TAX1BP1 binding not established\", \"Whether autophagy-receptor recruitment depends on the canonical Ragulator/mTOR function unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined a stage-specific requirement for LAMTOR2 in B-cell development driven by its control of BCR internalization and endosomal trafficking.\",\n      \"evidence\": \"Two independent conditional KO models (mb1-Cre, Cd19-Cre) with BCR internalization and endosomal trafficking assays\",\n      \"pmids\": [\"30936881\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the pre-B1 arrest reflects signaling vs trafficking failure not separated\", \"Effector linking BCR trafficking defect to aberrant signaling unidentified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected extracellular SCFA/GPR43 signaling to LAMTOR2-dependent phagosome-lysosome fusion and ERK activation in antimicrobial macrophage function.\",\n      \"evidence\": \"Macrophage-specific conditional Lamtor2 KO with SCFA/GPR43 stimulation, phagosome-lysosome fusion and ERK phosphorylation assays\",\n      \"pmids\": [\"33144310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional mechanism by which GPR43 upregulates LAMTOR2 not detailed\", \"Whether ERK and fusion functions are mechanistically coupled unaddressed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed LAMTOR2's mTOR-activating scaffold function can be amplified by a partner, VSIG2, that bridges LAMTOR2 and mTOR.\",\n      \"evidence\": \"Mass spectrometry and reciprocal co-IP with VSIG2 overexpression/knockdown and mTOR phosphorylation readouts in PDAC cells\",\n      \"pmids\": [\"37626304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the trimeric VSIG2–LAMTOR2–mTOR assembly unknown\", \"Single cancer-cell context; generality untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proposed a nuclear-signaling arm in which LAMTOR2 controls BCLAF1 nuclear translocation in chondrocytes affecting cartilage degradation.\",\n      \"evidence\": \"Immunoprecipitation/mass spectrometry and BCLAF1 nuclear translocation assay in chondrocytes\",\n      \"pmids\": [\"39990659\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP/MS identification without reciprocal validation\", \"Mechanism by which an endosomal scaffold controls nuclear translocation undefined\", \"Downstream cartilage-degradation pathway not mechanistically traced\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How LAMTOR2 partitions its scaffold time between Ragulator/mTOR signaling, receptor trafficking, autophagy-receptor recruitment, and motor-driven endosome positioning—and what determines context-specific output—remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of LAMTOR2 engaging its diverse partners across functions\", \"Rules governing which cargo/pathway LAMTOR2 serves in a given cell type unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 6, 9]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [4, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2, 5, 8]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 4, 7]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 2, 7, 8]}\n    ],\n    \"complexes\": [\"LAMTOR/Ragulator complex\", \"p14-MP1 (LAMTOR2/3) complex\"],\n    \"partners\": [\"LAMTOR3\", \"LAMTOR1\", \"TAX1BP1\", \"NBR1\", \"SQSTM1\", \"VSIG2\", \"MTOR\", \"BCLAF1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}