{"gene":"LGALS9","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2020,"finding":"Exosomal LGALS9 derived from glioblastoma cells binds to the TIM-3 receptor on dendritic cells in the cerebrospinal fluid, inhibiting antigen recognition, processing, and presentation by DCs, thereby preventing cytotoxic T-cell-mediated antitumor immune responses. Blocking exosomal LGALS9 secretion restored DC antigen-presenting activity and induced durable antitumor immunity in mice.","method":"Proteomics of CSF exosomes, receptor-ligand binding assay (TIM-3/LGALS9), in vivo mouse model with LGALS9 secretion blockade, functional DC and T-cell assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional in vivo rescue experiment and receptor-ligand identification, single lab with multiple methods","pmids":["33093453"],"is_preprint":false},{"year":2015,"finding":"Recombinant LGALS9 (rLGALS9) internalizes via early and late endosomes and accumulates in the lysosomal compartment of KRAS-mutant colorectal cancer cells, where it acts as a lysosomal inhibitor blocking autophagosome-lysosome fusion. This leads to autophagosome accumulation, excessive lysosomal swelling, and cell death selectively in KRAS-mutant (but not BRAF-mutant) CRC cells with elevated basal autophagic flux.","method":"Live cell imaging (endosomal/lysosomal tracking), autophagy flux assays, cell viability assays, genetic mutant cell lines (KRAS vs BRAF)","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mechanistic pathway placement with multiple orthogonal methods (imaging, flux assays, genetic cell lines), single lab","pmids":["26086204"],"is_preprint":false},{"year":2013,"finding":"Endothelial cells express five LGALS9 splice variants (including two novel ones) confined to exons 5, 6, and 10. Transfection of HMEC with the galectin-9Δ5 splice variant increased proliferation; exogenous recombinant galectin-9Δ5 protein dose-dependently reduced endothelial cell proliferation and migration in vitro and induced a small inhibitory effect on angiogenesis in vivo, while also enhancing sprouting toward a galectin-9Δ5 gradient.","method":"Transfection/overexpression in HMEC, recombinant protein treatment, in vitro proliferation and migration assays, in vivo angiogenesis assay","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function transfection and recombinant protein experiments with functional readouts, single lab","pmids":["24333696"],"is_preprint":false},{"year":2013,"finding":"The LGALS9 D5 isoform suppresses interferon-gamma production by decidual natural killer cells. Decidual LGALS9 expression is deregulated in a mouse model of spontaneous abortion, and decreased LGALS9 D5/10 isoform expression is associated with spontaneous abortion in humans.","method":"Real-time PCR, immunohistochemistry, functional NK cell cytokine assay (IFN-γ production), mouse model of spontaneous abortion","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional assay on NK cells with isoform-specific recombinant protein, mouse model with phenotypic readout, single lab","pmids":["23242525"],"is_preprint":false},{"year":2021,"finding":"Galectin-9 (Gal-9/LGALS9) binds to peroxiredoxin-2 (PRDX2) in a sugar chain-independent manner. In 3T3-L1 adipocytes, Gal-9 knockdown shifts PRDX2 from its oxidized dimer form to the reduced monomer form under oxidative stress. Lgals9-deficient mice are resistant to diet-induced obesity with reduced adipose tissue and improved glucose tolerance, and bone marrow transplant experiments indicate the effect is non-hematopoietic-cell-autonomous.","method":"nanoLC-MS/MS, co-immunoprecipitation, pull-down assay, Gal-9 knockdown in adipocytes, western blot (PRDX2 redox state), Lgals9 knockout mouse with bone marrow transplantation","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — binding identified by MS and confirmed by Co-IP/pull-down, functional KO mouse with BMT epistasis, single lab with multiple orthogonal methods","pmids":["33727589"],"is_preprint":false},{"year":2018,"finding":"Lgals9 deficiency in BALB/c mice protected against pristane-induced lupus nephritis, arthritis, and lipogranuloma formation without altering T-cell or B-cell subset composition in spleen or peritoneum, and without affecting the TLR7–type I interferon pathway. The protective effect was mediated through targeting of activated macrophages.","method":"Lgals9 knockout mouse model (pristane-induced lupus), histopathology, flow cytometry of immune subsets, cytokine profiling from peritoneal macrophages","journal":"Arthritis & rheumatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined phenotypic readouts and mechanistic pathway exclusion (TLR7/IFN pathway negative), single lab","pmids":["29481735"],"is_preprint":false},{"year":2021,"finding":"LGALS9 transcription in endometrial stromal cells is upregulated by HAND2 and downregulated by FOXO1. Phosphorylated FOXO1 (pFOXO1) cannot bind DNA and thus cannot directly suppress LGALS9 transcription, so the phosphorylation status of FOXO1 and expression of HAND2 together determine LGALS9 mRNA levels during decidualization.","method":"Promoter-reporter transcriptional activity assays, siRNA knockdown of HAND2 and FOXO1, RT-qPCR, phospho-FOXO1 chromatin binding assay","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — promoter reporter + knockdown experiments with mechanistic follow-up on FOXO1 phosphorylation/DNA binding, single lab","pmids":["34581822"],"is_preprint":false},{"year":2020,"finding":"Histone H3K9 and H3K14 acetylation at the LGALS9 promoter correlates with LGALS9 mRNA levels in cervical cancer cells, while CpG methylation at the promoter does not show hypermethylation associated with low LGALS9 expression. This suggests histone acetylation, not DNA methylation, is the primary epigenetic regulator of LGALS9 transcription.","method":"Chromatin immunoprecipitation (ChIP) for H3K9ac and H3K14ac, bisulfite sequencing for CpG methylation, RT-qPCR","journal":"FEBS open bio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ChIP correlation without functional perturbation experiment, single lab, single method per modification","pmids":["32902187"],"is_preprint":false},{"year":2025,"finding":"In early-stage endometrial cancer, CD47⁺ epithelial cells interact with macrophages through the CD47–HCK (Hemopoietic Cell Kinase) axis, driving macrophage secretion of LGALS9, IL-10, and TGF-β1. Macrophage-derived LGALS9 in turn reinforces EC cell proliferation via CD47, establishing a positive feedback loop (CD47–HCK–LGALS9). ERRγ was identified as an upstream transcriptional regulator of CD47, suppressible by progesterone.","method":"GST pull-down mass spectrometry, molecular docking, CUT&Tag (transcription factor identification), organoid–macrophage co-culture model, flow cytometry, CCK-8 proliferation assay","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods including pull-down MS, CUT&Tag, and organoid functional assay, single lab","pmids":["41437376"],"is_preprint":false},{"year":2025,"finding":"Rhamnose binds to sites V39, D40, and T101 of CEACAM1, promoting the interaction between CEACAM1 and LGALS9, which increases DUSP1 protein levels, inhibits p38 phosphorylation, and thereby attenuates LPS-triggered proinflammatory cytokine expression in macrophages.","method":"In vitro macrophage binding assays, Co-immunoprecipitation (CEACAM1–LGALS9), western blot (DUSP1, p-p38), LPS-induced endotoxic mouse model, site-directed mutagenesis/docking for binding sites","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP of CEACAM1–LGALS9 interaction with mechanistic downstream signaling validated in vitro and in vivo, single lab","pmids":["40708539"],"is_preprint":false},{"year":2025,"finding":"Recombinant Lgals9 (rLgals9) treatment polarized macrophages toward the M2b phenotype at appropriate concentrations in vitro, as validated by flow cytometry and ELISA. Single-cell RNA sequencing showed significant downregulation of Lgals9 in macrophages after mouse heart transplantation.","method":"Recombinant protein treatment of macrophages, flow cytometry (M2b polarization markers), ELISA, scRNA-seq, RT-qPCR, western blot","journal":"Journal of leukocyte biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, functional polarization assay with recombinant protein but limited mechanistic depth","pmids":["39835675"],"is_preprint":false},{"year":2025,"finding":"In gastric cancer, myeloid cell-derived LGALS9 binds to P4HB (beta-subunit of prolyl 4-hydroxylase) on epithelial cells as a ligand-receptor pair. Activation of P4HB by LGALS9 enhanced proliferation, epithelial-mesenchymal transition (EMT), and lipid metabolism in gastric cancer cells; pharmacological inhibition of P4HB reversed these effects.","method":"Single-cell RNA sequencing (ligand-receptor inference), functional experiments with LGALS9 treatment and P4HB inhibition, proliferation assays, EMT marker analysis","journal":"Journal of cellular and molecular medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ligand-receptor interaction inferred from scRNA-seq with functional validation of P4HB inhibition, but direct LGALS9–P4HB binding not confirmed by Co-IP/pull-down in abstract, single lab","pmids":["40534096"],"is_preprint":false},{"year":2026,"finding":"LGALS9 blockade (via adenoviral immunization) enhanced dendritic cell activation and maturation (upregulating CD80, CD86, MHC-II, CD40), promoted CD8+ T-cell priming and expansion, and disrupted the LGALS9/TIM-3 inhibitory axis via neutralizing antibodies, alleviating T-cell exhaustion in prostate cancer models.","method":"Adenoviral vector immunization, flow cytometry, ELISA, ELISpot, cytotoxic T lymphocyte assay, cell depletion experiments, in vivo mouse tumor models","journal":"Journal for immunotherapy of cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal functional assays in vivo and in vitro including depletion experiments confirming mechanism, single lab","pmids":["42103355"],"is_preprint":false},{"year":2024,"finding":"In osteoarthritis, LGALS9 exacerbates inflammatory responses by activating JNK and ERK1/2 (MAPK) signaling pathways. RNAi-mediated knockdown and lentiviral overexpression/knockdown in in vitro and in vivo OA models confirmed this regulatory role.","method":"RNAi knockdown, lentiviral overexpression/knockdown, western blot, qRT-PCR, immunofluorescence, safranin fast green staining, in vivo OA model","journal":"International journal of biological macromolecules","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss- and gain-of-function with pathway-level readouts in both in vitro and in vivo models, single lab","pmids":["39278441"],"is_preprint":false}],"current_model":"LGALS9 (Galectin-9) is a secreted/cell-associated lectin that functions as a TIM-3 ligand to suppress dendritic cell antigen presentation and T-cell immunity (including via exosomal delivery), acts as a lysosomal inhibitor that blocks autophagosome-lysosome fusion in KRAS-mutant cancer cells, binds PRDX2 in a carbohydrate-independent manner to modulate adipocyte redox state, interacts with CEACAM1 to suppress p38-mediated inflammation via DUSP1, drives macrophage LGALS9 secretion through a CD47–HCK positive feedback loop in endometrial cancer, and has its transcription regulated by HAND2 (activator) and FOXO1 (repressor) in endometrial stromal cells and by histone H3K9/H3K14 acetylation at its promoter."},"narrative":{"mechanistic_narrative":"LGALS9 (Galectin-9) is a secreted, cell-associated lectin that operates primarily as an immunomodulatory ligand shaping innate and adaptive immune responses across cancer, reproduction, and inflammatory disease [PMID:33093453, PMID:42103355]. As a ligand for the TIM-3 receptor, tumor-derived LGALS9—including via exosomal delivery from glioblastoma cells—suppresses dendritic cell antigen presentation and cytotoxic T-cell priming, and disrupting this axis restores DC maturation and durable antitumor immunity [PMID:33093453, PMID:42103355]. Beyond TIM-3, LGALS9 engages multiple partners to direct context-specific signaling: it binds peroxiredoxin-2 (PRDX2) in a carbohydrate-independent manner to control adipocyte redox state and diet-induced obesity [PMID:33727589], and rhamnose-promoted association with CEACAM1 raises DUSP1 levels to dampen p38-driven proinflammatory cytokine production in macrophages [PMID:40708539]. It also acts cell-intrinsically: internalized recombinant LGALS9 accumulates in lysosomes and blocks autophagosome-lysosome fusion, selectively killing KRAS-mutant colorectal cancer cells with high basal autophagic flux [PMID:26086204]. In tumor microenvironments, myeloid-derived LGALS9 reinforces epithelial proliferation through a CD47–HCK feedback loop in endometrial cancer [PMID:41437376], and its loss is protective in pristane-induced lupus by targeting activated macrophages [PMID:29481735]. Genetic deletion phenotypes and isoform-specific functions in NK-cell cytokine suppression establish roles in reproduction and decidualization [PMID:23242525], where LGALS9 transcription is jointly controlled by HAND2 activation and FOXO1 repression [PMID:34581822]. LGALS9 also exacerbates inflammation through JNK and ERK1/2 MAPK signaling in osteoarthritis [PMID:39278441].","teleology":[{"year":2013,"claim":"Established that distinct LGALS9 splice isoforms carry separable functions in vascular and immune contexts, moving the gene beyond a single monolithic activity.","evidence":"Splice variant cloning, HMEC transfection, and recombinant protein assays for proliferation/migration/angiogenesis, plus isoform-specific NK-cell IFN-γ assays and a mouse abortion model","pmids":["24333696","23242525"],"confidence":"Medium","gaps":["Receptors mediating isoform-specific effects not identified","Molecular basis for opposite proliferation/migration outcomes of the same isoform unresolved"]},{"year":2015,"claim":"Showed a cell-intrinsic, lysosome-based mechanism distinct from extracellular ligand signaling, defining LGALS9 as an inhibitor of autophagosome-lysosome fusion that is selectively lethal to KRAS-mutant cells.","evidence":"Endosomal/lysosomal live-cell imaging, autophagy flux and viability assays in KRAS- vs BRAF-mutant colorectal cancer lines","pmids":["26086204"],"confidence":"Medium","gaps":["Molecular target within the lysosome not identified","Mechanism of KRAS-selectivity beyond elevated autophagic flux unclear"]},{"year":2018,"claim":"Defined the immune cell type through which LGALS9 drives autoimmune pathology, showing macrophages rather than lymphocyte subsets or the TLR7–IFN axis mediate disease.","evidence":"Lgals9 knockout in pristane-induced lupus mice with histopathology, immune subset flow cytometry, and pathway exclusion","pmids":["29481735"],"confidence":"Medium","gaps":["Macrophage receptor for LGALS9 in this setting not identified","Downstream signaling in activated macrophages not mapped"]},{"year":2020,"claim":"Identified exosomal delivery of LGALS9 as a route for tumor immune evasion via the TIM-3 axis on dendritic cells, and showed transcription is governed primarily by histone acetylation rather than DNA methylation.","evidence":"CSF exosome proteomics, TIM-3/LGALS9 binding assays, and in vivo secretion blockade; separately ChIP for H3K9ac/H3K14ac and bisulfite sequencing in cervical cancer cells","pmids":["33093453","32902187"],"confidence":"Medium","gaps":["Mechanism of LGALS9 packaging into exosomes unknown","Histone acetylation finding is correlative without functional perturbation (Low confidence)"]},{"year":2021,"claim":"Revealed carbohydrate-independent partnerships and transcriptional control, identifying PRDX2 binding that links LGALS9 to redox/metabolic regulation and a HAND2/FOXO1 logic gate governing its expression during decidualization.","evidence":"nanoLC-MS/MS, Co-IP and pull-down with PRDX2 redox western blots, Lgals9 KO mice with bone marrow transplant; promoter-reporter and siRNA knockdown of HAND2/FOXO1 with phospho-FOXO1 DNA-binding assays","pmids":["33727589","34581822"],"confidence":"Medium","gaps":["How PRDX2 binding alters its oxidation state mechanistically unresolved","Direct vs indirect transcriptional control by HAND2 not fully separated"]},{"year":2025,"claim":"Expanded the partner repertoire and tumor-microenvironment roles, identifying CEACAM1 and P4HB as interactors and a CD47–HCK–LGALS9 macrophage-epithelial feedback loop.","evidence":"Co-IP (CEACAM1) with DUSP1/p-p38 readouts and LPS endotoxic model; GST pull-down MS and CUT&Tag with organoid-macrophage co-culture (CD47–HCK); scRNA-seq ligand-receptor inference plus P4HB inhibition for gastric cancer","pmids":["40708539","41437376","40534096"],"confidence":"Medium","gaps":["Direct LGALS9–P4HB binding not confirmed biochemically (Low confidence)","Whether CEACAM1 and CD47 effects share a common signaling node unknown"]},{"year":2025,"claim":"Linked LGALS9 to macrophage polarization and MAPK-driven inflammation, broadening its functional output to M2b polarization and JNK/ERK1/2 activation.","evidence":"Recombinant Lgals9 macrophage polarization assays with scRNA-seq (heart transplant); RNAi and lentiviral gain/loss-of-function with MAPK western blots in osteoarthritis models","pmids":["39835675","39278441"],"confidence":"Medium","gaps":["M2b polarization mechanism lacks mechanistic depth (Low confidence)","Receptor coupling LGALS9 to JNK/ERK1/2 not defined"]},{"year":2026,"claim":"Validated therapeutic disruption of the LGALS9/TIM-3 axis, showing blockade reverses T-cell exhaustion and enhances DC maturation and CD8+ T-cell priming.","evidence":"Adenoviral immunization, neutralizing antibodies, ELISpot, CTL assays, and cell-depletion experiments in prostate cancer mouse models","pmids":["42103355"],"confidence":"Medium","gaps":["Relative contribution of TIM-3 vs other LGALS9 partners to exhaustion not isolated","Durability and resistance mechanisms not assessed"]},{"year":null,"claim":"A unifying biochemical account of how a single lectin selects among TIM-3, PRDX2, CEACAM1, CD47-axis, and P4HB partners—and toggles between extracellular ligand signaling and intracellular lysosomal inhibition—remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural basis for partner selectivity","Determinants of secretion vs internalization vs exosomal packaging unknown","Carbohydrate-dependent vs independent binding modes not systematically compared"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[0,11,12]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,4,9]}],"localization":[{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[1]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,8]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,5,12]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[9,13]}],"complexes":[],"partners":["HAVCR2","PRDX2","CEACAM1","CD47","P4HB","HAND2","FOXO1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O00182","full_name":"Galectin-9","aliases":["Ecalectin","Tumor antigen HOM-HD-21"],"length_aa":355,"mass_kda":39.5,"function":"Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) death (PubMed:16286920). Also stimulates bactericidal activity in infected macrophages by causing macrophage activation and IL1B secretion which restricts intracellular bacterial growth (By similarity). Ligand for P4HB; the interaction retains P4HB at the cell surface of Th2 T-helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). Ligand for CD44; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (By similarity). Promotes ability of mesenchymal stromal cells to suppress T-cell proliferation (PubMed:23817958). Expands regulatory T-cells and induces cytotoxic T-cell apoptosis following virus infection (PubMed:20209097). Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) and chemokine (CCL2) production in mast and dendritic cells (PubMed:16116184, PubMed:24465902). Inhibits degranulation and induces apoptosis of mast cells (PubMed:24465902). Induces maturation and migration of dendritic cells (PubMed:16116184, PubMed:25754930). Inhibits natural killer (NK) cell function (PubMed:23408620). Can transform NK cell phenotype from peripheral to decidual during pregnancy (PubMed:25578313). Astrocyte derived galectin-9 enhances microglial TNF production (By similarity). May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. May provide the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion (By similarity). Highly selective to the anion urate (By similarity) Acts as an eosinophil chemoattractant (PubMed:9642261). It also inhibits angiogenesis (PubMed:24333696). Suppresses IFNG production by natural killer cells (By similarity)","subcellular_location":"Secreted","url":"https://www.uniprot.org/uniprotkb/O00182/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LGALS9","classification":"Not Classified","n_dependent_lines":34,"n_total_lines":1208,"dependency_fraction":0.028145695364238412},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/LGALS9","total_profiled":1310},"omim":[{"mim_id":"606652","title":"HEPATITIS A VIRUS CELLULAR RECEPTOR 2; HAVCR2","url":"https://www.omim.org/entry/606652"},{"mim_id":"606096","title":"LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 12; LGALS12","url":"https://www.omim.org/entry/606096"},{"mim_id":"601879","title":"LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 9; LGALS9","url":"https://www.omim.org/entry/601879"},{"mim_id":"153619","title":"LECTIN, GALACTOSIDE-BINDING, SOLUBLE, 3; LGALS3","url":"https://www.omim.org/entry/153619"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"intestine","ntpm":92.9},{"tissue":"stomach 1","ntpm":82.6}],"url":"https://www.proteinatlas.org/search/LGALS9"},"hgnc":{"alias_symbol":["LGALS9A"],"prev_symbol":[]},"alphafold":{"accession":"O00182","domains":[{"cath_id":"2.60.120.200","chopping":"11-149","consensus_level":"high","plddt":97.0732,"start":11,"end":149},{"cath_id":"2.60.120.200","chopping":"228-355","consensus_level":"high","plddt":97.6511,"start":228,"end":355}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00182","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00182-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00182-F1-predicted_aligned_error_v6.png","plddt_mean":84.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LGALS9","jax_strain_url":"https://www.jax.org/strain/search?query=LGALS9"},"sequence":{"accession":"O00182","fasta_url":"https://rest.uniprot.org/uniprotkb/O00182.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00182/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00182"}},"corpus_meta":[{"pmid":"37554219","id":"PMC_37554219","title":"A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).","date":"2022","source":"Genes & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/37554219","citation_count":125,"is_preprint":false},{"pmid":"33093453","id":"PMC_33093453","title":"Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/33093453","citation_count":98,"is_preprint":false},{"pmid":"31747929","id":"PMC_31747929","title":"Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma.","date":"2019","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/31747929","citation_count":59,"is_preprint":false},{"pmid":"24333696","id":"PMC_24333696","title":"Endothelial LGALS9 splice variant expression in endothelial cell biology and 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glioblastoma cells binds to the TIM-3 receptor on dendritic cells in the cerebrospinal fluid, inhibiting antigen recognition, processing, and presentation by DCs, thereby preventing cytotoxic T-cell-mediated antitumor immune responses. Blocking exosomal LGALS9 secretion restored DC antigen-presenting activity and induced durable antitumor immunity in mice.\",\n      \"method\": \"Proteomics of CSF exosomes, receptor-ligand binding assay (TIM-3/LGALS9), in vivo mouse model with LGALS9 secretion blockade, functional DC and T-cell assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional in vivo rescue experiment and receptor-ligand identification, single lab with multiple methods\",\n      \"pmids\": [\"33093453\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Recombinant LGALS9 (rLGALS9) internalizes via early and late endosomes and accumulates in the lysosomal compartment of KRAS-mutant colorectal cancer cells, where it acts as a lysosomal inhibitor blocking autophagosome-lysosome fusion. This leads to autophagosome accumulation, excessive lysosomal swelling, and cell death selectively in KRAS-mutant (but not BRAF-mutant) CRC cells with elevated basal autophagic flux.\",\n      \"method\": \"Live cell imaging (endosomal/lysosomal tracking), autophagy flux assays, cell viability assays, genetic mutant cell lines (KRAS vs BRAF)\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mechanistic pathway placement with multiple orthogonal methods (imaging, flux assays, genetic cell lines), single lab\",\n      \"pmids\": [\"26086204\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Endothelial cells express five LGALS9 splice variants (including two novel ones) confined to exons 5, 6, and 10. Transfection of HMEC with the galectin-9Δ5 splice variant increased proliferation; exogenous recombinant galectin-9Δ5 protein dose-dependently reduced endothelial cell proliferation and migration in vitro and induced a small inhibitory effect on angiogenesis in vivo, while also enhancing sprouting toward a galectin-9Δ5 gradient.\",\n      \"method\": \"Transfection/overexpression in HMEC, recombinant protein treatment, in vitro proliferation and migration assays, in vivo angiogenesis assay\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function transfection and recombinant protein experiments with functional readouts, single lab\",\n      \"pmids\": [\"24333696\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The LGALS9 D5 isoform suppresses interferon-gamma production by decidual natural killer cells. Decidual LGALS9 expression is deregulated in a mouse model of spontaneous abortion, and decreased LGALS9 D5/10 isoform expression is associated with spontaneous abortion in humans.\",\n      \"method\": \"Real-time PCR, immunohistochemistry, functional NK cell cytokine assay (IFN-γ production), mouse model of spontaneous abortion\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional assay on NK cells with isoform-specific recombinant protein, mouse model with phenotypic readout, single lab\",\n      \"pmids\": [\"23242525\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Galectin-9 (Gal-9/LGALS9) binds to peroxiredoxin-2 (PRDX2) in a sugar chain-independent manner. In 3T3-L1 adipocytes, Gal-9 knockdown shifts PRDX2 from its oxidized dimer form to the reduced monomer form under oxidative stress. Lgals9-deficient mice are resistant to diet-induced obesity with reduced adipose tissue and improved glucose tolerance, and bone marrow transplant experiments indicate the effect is non-hematopoietic-cell-autonomous.\",\n      \"method\": \"nanoLC-MS/MS, co-immunoprecipitation, pull-down assay, Gal-9 knockdown in adipocytes, western blot (PRDX2 redox state), Lgals9 knockout mouse with bone marrow transplantation\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — binding identified by MS and confirmed by Co-IP/pull-down, functional KO mouse with BMT epistasis, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"33727589\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Lgals9 deficiency in BALB/c mice protected against pristane-induced lupus nephritis, arthritis, and lipogranuloma formation without altering T-cell or B-cell subset composition in spleen or peritoneum, and without affecting the TLR7–type I interferon pathway. The protective effect was mediated through targeting of activated macrophages.\",\n      \"method\": \"Lgals9 knockout mouse model (pristane-induced lupus), histopathology, flow cytometry of immune subsets, cytokine profiling from peritoneal macrophages\",\n      \"journal\": \"Arthritis & rheumatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined phenotypic readouts and mechanistic pathway exclusion (TLR7/IFN pathway negative), single lab\",\n      \"pmids\": [\"29481735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"LGALS9 transcription in endometrial stromal cells is upregulated by HAND2 and downregulated by FOXO1. Phosphorylated FOXO1 (pFOXO1) cannot bind DNA and thus cannot directly suppress LGALS9 transcription, so the phosphorylation status of FOXO1 and expression of HAND2 together determine LGALS9 mRNA levels during decidualization.\",\n      \"method\": \"Promoter-reporter transcriptional activity assays, siRNA knockdown of HAND2 and FOXO1, RT-qPCR, phospho-FOXO1 chromatin binding assay\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — promoter reporter + knockdown experiments with mechanistic follow-up on FOXO1 phosphorylation/DNA binding, single lab\",\n      \"pmids\": [\"34581822\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Histone H3K9 and H3K14 acetylation at the LGALS9 promoter correlates with LGALS9 mRNA levels in cervical cancer cells, while CpG methylation at the promoter does not show hypermethylation associated with low LGALS9 expression. This suggests histone acetylation, not DNA methylation, is the primary epigenetic regulator of LGALS9 transcription.\",\n      \"method\": \"Chromatin immunoprecipitation (ChIP) for H3K9ac and H3K14ac, bisulfite sequencing for CpG methylation, RT-qPCR\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ChIP correlation without functional perturbation experiment, single lab, single method per modification\",\n      \"pmids\": [\"32902187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In early-stage endometrial cancer, CD47⁺ epithelial cells interact with macrophages through the CD47–HCK (Hemopoietic Cell Kinase) axis, driving macrophage secretion of LGALS9, IL-10, and TGF-β1. Macrophage-derived LGALS9 in turn reinforces EC cell proliferation via CD47, establishing a positive feedback loop (CD47–HCK–LGALS9). ERRγ was identified as an upstream transcriptional regulator of CD47, suppressible by progesterone.\",\n      \"method\": \"GST pull-down mass spectrometry, molecular docking, CUT&Tag (transcription factor identification), organoid–macrophage co-culture model, flow cytometry, CCK-8 proliferation assay\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods including pull-down MS, CUT&Tag, and organoid functional assay, single lab\",\n      \"pmids\": [\"41437376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Rhamnose binds to sites V39, D40, and T101 of CEACAM1, promoting the interaction between CEACAM1 and LGALS9, which increases DUSP1 protein levels, inhibits p38 phosphorylation, and thereby attenuates LPS-triggered proinflammatory cytokine expression in macrophages.\",\n      \"method\": \"In vitro macrophage binding assays, Co-immunoprecipitation (CEACAM1–LGALS9), western blot (DUSP1, p-p38), LPS-induced endotoxic mouse model, site-directed mutagenesis/docking for binding sites\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of CEACAM1–LGALS9 interaction with mechanistic downstream signaling validated in vitro and in vivo, single lab\",\n      \"pmids\": [\"40708539\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Recombinant Lgals9 (rLgals9) treatment polarized macrophages toward the M2b phenotype at appropriate concentrations in vitro, as validated by flow cytometry and ELISA. Single-cell RNA sequencing showed significant downregulation of Lgals9 in macrophages after mouse heart transplantation.\",\n      \"method\": \"Recombinant protein treatment of macrophages, flow cytometry (M2b polarization markers), ELISA, scRNA-seq, RT-qPCR, western blot\",\n      \"journal\": \"Journal of leukocyte biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, functional polarization assay with recombinant protein but limited mechanistic depth\",\n      \"pmids\": [\"39835675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In gastric cancer, myeloid cell-derived LGALS9 binds to P4HB (beta-subunit of prolyl 4-hydroxylase) on epithelial cells as a ligand-receptor pair. Activation of P4HB by LGALS9 enhanced proliferation, epithelial-mesenchymal transition (EMT), and lipid metabolism in gastric cancer cells; pharmacological inhibition of P4HB reversed these effects.\",\n      \"method\": \"Single-cell RNA sequencing (ligand-receptor inference), functional experiments with LGALS9 treatment and P4HB inhibition, proliferation assays, EMT marker analysis\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ligand-receptor interaction inferred from scRNA-seq with functional validation of P4HB inhibition, but direct LGALS9–P4HB binding not confirmed by Co-IP/pull-down in abstract, single lab\",\n      \"pmids\": [\"40534096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"LGALS9 blockade (via adenoviral immunization) enhanced dendritic cell activation and maturation (upregulating CD80, CD86, MHC-II, CD40), promoted CD8+ T-cell priming and expansion, and disrupted the LGALS9/TIM-3 inhibitory axis via neutralizing antibodies, alleviating T-cell exhaustion in prostate cancer models.\",\n      \"method\": \"Adenoviral vector immunization, flow cytometry, ELISA, ELISpot, cytotoxic T lymphocyte assay, cell depletion experiments, in vivo mouse tumor models\",\n      \"journal\": \"Journal for immunotherapy of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal functional assays in vivo and in vitro including depletion experiments confirming mechanism, single lab\",\n      \"pmids\": [\"42103355\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In osteoarthritis, LGALS9 exacerbates inflammatory responses by activating JNK and ERK1/2 (MAPK) signaling pathways. RNAi-mediated knockdown and lentiviral overexpression/knockdown in in vitro and in vivo OA models confirmed this regulatory role.\",\n      \"method\": \"RNAi knockdown, lentiviral overexpression/knockdown, western blot, qRT-PCR, immunofluorescence, safranin fast green staining, in vivo OA model\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss- and gain-of-function with pathway-level readouts in both in vitro and in vivo models, single lab\",\n      \"pmids\": [\"39278441\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LGALS9 (Galectin-9) is a secreted/cell-associated lectin that functions as a TIM-3 ligand to suppress dendritic cell antigen presentation and T-cell immunity (including via exosomal delivery), acts as a lysosomal inhibitor that blocks autophagosome-lysosome fusion in KRAS-mutant cancer cells, binds PRDX2 in a carbohydrate-independent manner to modulate adipocyte redox state, interacts with CEACAM1 to suppress p38-mediated inflammation via DUSP1, drives macrophage LGALS9 secretion through a CD47–HCK positive feedback loop in endometrial cancer, and has its transcription regulated by HAND2 (activator) and FOXO1 (repressor) in endometrial stromal cells and by histone H3K9/H3K14 acetylation at its promoter.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LGALS9 (Galectin-9) is a secreted, cell-associated lectin that operates primarily as an immunomodulatory ligand shaping innate and adaptive immune responses across cancer, reproduction, and inflammatory disease [#0, #12]. As a ligand for the TIM-3 receptor, tumor-derived LGALS9—including via exosomal delivery from glioblastoma cells—suppresses dendritic cell antigen presentation and cytotoxic T-cell priming, and disrupting this axis restores DC maturation and durable antitumor immunity [#0, #12]. Beyond TIM-3, LGALS9 engages multiple partners to direct context-specific signaling: it binds peroxiredoxin-2 (PRDX2) in a carbohydrate-independent manner to control adipocyte redox state and diet-induced obesity [#4], and rhamnose-promoted association with CEACAM1 raises DUSP1 levels to dampen p38-driven proinflammatory cytokine production in macrophages [#9]. It also acts cell-intrinsically: internalized recombinant LGALS9 accumulates in lysosomes and blocks autophagosome-lysosome fusion, selectively killing KRAS-mutant colorectal cancer cells with high basal autophagic flux [#1]. In tumor microenvironments, myeloid-derived LGALS9 reinforces epithelial proliferation through a CD47–HCK feedback loop in endometrial cancer [#8], and its loss is protective in pristane-induced lupus by targeting activated macrophages [#5]. Genetic deletion phenotypes and isoform-specific functions in NK-cell cytokine suppression establish roles in reproduction and decidualization [#3], where LGALS9 transcription is jointly controlled by HAND2 activation and FOXO1 repression [#6]. LGALS9 also exacerbates inflammation through JNK and ERK1/2 MAPK signaling in osteoarthritis [#13].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that distinct LGALS9 splice isoforms carry separable functions in vascular and immune contexts, moving the gene beyond a single monolithic activity.\",\n      \"evidence\": \"Splice variant cloning, HMEC transfection, and recombinant protein assays for proliferation/migration/angiogenesis, plus isoform-specific NK-cell IFN-γ assays and a mouse abortion model\",\n      \"pmids\": [\"24333696\", \"23242525\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Receptors mediating isoform-specific effects not identified\", \"Molecular basis for opposite proliferation/migration outcomes of the same isoform unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showed a cell-intrinsic, lysosome-based mechanism distinct from extracellular ligand signaling, defining LGALS9 as an inhibitor of autophagosome-lysosome fusion that is selectively lethal to KRAS-mutant cells.\",\n      \"evidence\": \"Endosomal/lysosomal live-cell imaging, autophagy flux and viability assays in KRAS- vs BRAF-mutant colorectal cancer lines\",\n      \"pmids\": [\"26086204\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular target within the lysosome not identified\", \"Mechanism of KRAS-selectivity beyond elevated autophagic flux unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined the immune cell type through which LGALS9 drives autoimmune pathology, showing macrophages rather than lymphocyte subsets or the TLR7–IFN axis mediate disease.\",\n      \"evidence\": \"Lgals9 knockout in pristane-induced lupus mice with histopathology, immune subset flow cytometry, and pathway exclusion\",\n      \"pmids\": [\"29481735\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Macrophage receptor for LGALS9 in this setting not identified\", \"Downstream signaling in activated macrophages not mapped\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified exosomal delivery of LGALS9 as a route for tumor immune evasion via the TIM-3 axis on dendritic cells, and showed transcription is governed primarily by histone acetylation rather than DNA methylation.\",\n      \"evidence\": \"CSF exosome proteomics, TIM-3/LGALS9 binding assays, and in vivo secretion blockade; separately ChIP for H3K9ac/H3K14ac and bisulfite sequencing in cervical cancer cells\",\n      \"pmids\": [\"33093453\", \"32902187\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of LGALS9 packaging into exosomes unknown\", \"Histone acetylation finding is correlative without functional perturbation (Low confidence)\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed carbohydrate-independent partnerships and transcriptional control, identifying PRDX2 binding that links LGALS9 to redox/metabolic regulation and a HAND2/FOXO1 logic gate governing its expression during decidualization.\",\n      \"evidence\": \"nanoLC-MS/MS, Co-IP and pull-down with PRDX2 redox western blots, Lgals9 KO mice with bone marrow transplant; promoter-reporter and siRNA knockdown of HAND2/FOXO1 with phospho-FOXO1 DNA-binding assays\",\n      \"pmids\": [\"33727589\", \"34581822\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How PRDX2 binding alters its oxidation state mechanistically unresolved\", \"Direct vs indirect transcriptional control by HAND2 not fully separated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Expanded the partner repertoire and tumor-microenvironment roles, identifying CEACAM1 and P4HB as interactors and a CD47–HCK–LGALS9 macrophage-epithelial feedback loop.\",\n      \"evidence\": \"Co-IP (CEACAM1) with DUSP1/p-p38 readouts and LPS endotoxic model; GST pull-down MS and CUT&Tag with organoid-macrophage co-culture (CD47–HCK); scRNA-seq ligand-receptor inference plus P4HB inhibition for gastric cancer\",\n      \"pmids\": [\"40708539\", \"41437376\", \"40534096\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct LGALS9–P4HB binding not confirmed biochemically (Low confidence)\", \"Whether CEACAM1 and CD47 effects share a common signaling node unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked LGALS9 to macrophage polarization and MAPK-driven inflammation, broadening its functional output to M2b polarization and JNK/ERK1/2 activation.\",\n      \"evidence\": \"Recombinant Lgals9 macrophage polarization assays with scRNA-seq (heart transplant); RNAi and lentiviral gain/loss-of-function with MAPK western blots in osteoarthritis models\",\n      \"pmids\": [\"39835675\", \"39278441\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"M2b polarization mechanism lacks mechanistic depth (Low confidence)\", \"Receptor coupling LGALS9 to JNK/ERK1/2 not defined\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Validated therapeutic disruption of the LGALS9/TIM-3 axis, showing blockade reverses T-cell exhaustion and enhances DC maturation and CD8+ T-cell priming.\",\n      \"evidence\": \"Adenoviral immunization, neutralizing antibodies, ELISpot, CTL assays, and cell-depletion experiments in prostate cancer mouse models\",\n      \"pmids\": [\"42103355\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relative contribution of TIM-3 vs other LGALS9 partners to exhaustion not isolated\", \"Durability and resistance mechanisms not assessed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying biochemical account of how a single lectin selects among TIM-3, PRDX2, CEACAM1, CD47-axis, and P4HB partners—and toggles between extracellular ligand signaling and intracellular lysosomal inhibition—remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural basis for partner selectivity\", \"Determinants of secretion vs internalization vs exosomal packaging unknown\", \"Carbohydrate-dependent vs independent binding modes not systematically compared\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [0, 11, 12]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 4, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 5, 12]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [9, 13]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"HAVCR2\", \"PRDX2\", \"CEACAM1\", \"CD47\", \"P4HB\", \"HAND2\", \"FOXO1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}