{"gene":"LAMP5","run_date":"2026-04-28T18:30:27","timeline":{"discoveries":[{"year":2007,"finding":"UNC-46 (LAMP5 ortholog in C. elegans) is a sorting factor that localizes the vesicular GABA transporter (UNC-47/VGAT) to synaptic vesicles; in unc-46 mutants, the transporter is diffusely spread along the axon rather than concentrated at synaptic vesicles, reducing miniature current frequency without affecting amplitude. The transporter recruits UNC-46 to synaptic vesicle precursors in the cell body, and UNC-46 sorts the transporter both at the cell body and during endocytosis at the synapse.","method":"Genetic loss-of-function (unc-46 mutants), electrophysiology (miniature currents), fluorescence localization of transporter in axons","journal":"Nature neuroscience","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype, electrophysiology, and localization; replicated concept in multiple follow-up studies","pmids":["17558401"],"is_preprint":false},{"year":2007,"finding":"BAD-LAMP (LAMP5) defines a novel early endocytic compartment in cortical projection neurons distinct from classical lysosomal/endosomal compartments. It is endocytosed and recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. A cryptic lysosomal retention motif in the cytoplasmic tail is actively counteracted by sorting signals that keep LAMP5 away from lysosomes.","method":"GFP-fusion protein subcellular localization, endocytosis assay in primary neurons and transfected HeLa cells, dynamin/AP2 inhibition experiments","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization experiment with functional consequence, single lab, multiple methods","pmids":["17215451"],"is_preprint":false},{"year":2011,"finding":"In human plasmacytoid dendritic cells (pDCs), BAD-LAMP (LAMP5) is localized in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and is rapidly lost upon activation by CpG oligonucleotides.","method":"Immunofluorescence colocalization with ERGIC markers, flow cytometry on freshly isolated CD123+ pDCs before and after CpG stimulation","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization experiment in primary human cells with functional context (activation-linked loss)","pmids":["21642595"],"is_preprint":false},{"year":2016,"finding":"In the mouse brain, LAMP5 is expressed in subpopulations of GABAergic forebrain neurons and is present at synaptic terminals overlapping with VGAT. LAMP5-deficient mice show altered short-term synaptic plasticity in GABAergic transmission, decreased anxiety, and deficits in olfactory discrimination, but VGAT localization is unaffected, indicating LAMP5 is not required for VGAT trafficking in mammals (unlike its C. elegans ortholog UNC-46).","method":"LAMP5 knockout mouse, electrophysiology (short-term plasticity), immunofluorescence colocalization with VGAT, behavioral assays","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined electrophysiological and behavioral phenotypes, multiple orthogonal methods","pmids":["27272053"],"is_preprint":false},{"year":2017,"finding":"BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human pDCs, promoting NF-κB activation and TNF production upon DNA detection. BAD-LAMP silencing enhances TLR9 retention in an inducible VAMP3+/LAMP2+/LAMP1- endolysosomal compartment, increasing type I interferon (IFN) signaling. Sustained BAD-LAMP expression thus limits type I IFN production by sorting TLR9 to late endosomes away from the IFN-promoting compartment.","method":"siRNA silencing of LAMP5 in primary human pDCs, TLR9 colocalization by immunofluorescence, cytokine measurement (IFN, TNF), TGF-β treatment and tumor-derived pDC analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — KD with defined molecular and functional readouts in primary human cells, multiple orthogonal approaches, replicated in tumor microenvironment context","pmids":["29030552"],"is_preprint":false},{"year":2019,"finding":"LAMP5 is a direct transcriptional target of DOT1L (H3K79 histone methyltransferase) in MLL leukemia and functions as an autophagic suppressor that protects MLL fusion proteins from autophagic degradation. Knockdown of LAMP5 promotes selective autophagic degradation of MLL oncoproteins.","method":"ChIP (DOT1L at LAMP5 locus), LAMP5 knockdown in leukemia cell lines and primary cells, autophagy flux assays (LC3, autophagic degradation), DOT1L inhibitor treatment, in vivo mouse leukemia model","journal":"Clinical cancer research","confidence":"High","confidence_rationale":"Tier 2 — ChIP establishes direct transcriptional regulation, KD with defined autophagic phenotype confirmed in vitro and in vivo","pmids":["30651276"],"is_preprint":false},{"year":2019,"finding":"LAMP5 is expressed exclusively in inhibitory (GABAergic/glycinergic) synaptic terminals in the brainstem and spinal cord. LAMP5 knockout mice show increased auditory and tactile startle responses and larger auditory brainstem response wave amplitudes, consistent with a role in sensorimotor inhibitory processing. VIAAT localization is unaffected in LAMP5 KO, confirming no conserved role in VIAAT trafficking.","method":"Lamp5 knockout mouse, auditory brainstem response (ABR) recording, acoustic and tactile startle reflex assays, immunofluorescence colocalization with VIAAT","journal":"Molecular brain","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined electrophysiological and behavioral phenotype, single lab","pmids":["30867010"],"is_preprint":false},{"year":2022,"finding":"LAMP5 modulates innate immune signaling in MLL-rearranged leukemia by transferring signal flux from interferon signaling endosomes to pro-inflammatory signaling endosomes. LAMP5 depletion inhibits NF-κB signaling and increases type I interferon signaling downstream of TLR/IL-1R activation. IRF7 depletion partially rescues the growth inhibition caused by LAMP5 knockdown (epistasis). LAMP5 is also detectable on the cell surface of MLL-r leukemia cells.","method":"LAMP5 knockdown in MLL-r leukemia cell lines, NF-κB and IFN pathway reporter assays, IRF7 double-knockdown epistasis, in vivo leukemia model, antibody-drug conjugate targeting surface LAMP5","journal":"Haematologica","confidence":"Medium","confidence_rationale":"Tier 2 — KD with pathway-level readouts and epistasis, single lab with multiple complementary methods","pmids":["33910331"],"is_preprint":false},{"year":2023,"finding":"LAMP5 interacts with ANXA7, and this interaction is disrupted by an Asp411 mutation in ANXA7. LAMP5 overexpression stabilizes lysosomal acidic environment and promotes autophagy flux, counteracting the effects of ANXA7 downregulation on autophagy inhibition and apoptosis activation after OGD/R injury in neurons. ANXA7 activation stabilizes LAMP5 protein expression.","method":"Co-immunoprecipitation (ANXA7-LAMP5 interaction), Asp411 mutation analysis, LAMP5 overexpression in OGD/R neuronal model, lysosomal acidification assay, autophagy flux assay, apoptosis assay","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 3 — Co-IP establishes interaction, overexpression with functional readouts, single lab","pmids":["37620352"],"is_preprint":false},{"year":2024,"finding":"LAMP5-AS1 lncRNA recruits the H3K79 histone methyltransferase DOT1L to the LAMP5 locus, directly activating LAMP5 transcription. Blocking the LAMP5-AS1–LAMP5 axis enhances autophagic degradation of MLL fusion proteins.","method":"ChIRP assay (LAMP5-AS1 at LAMP5 locus), ChIP (DOT1L/H3K79me2 at LAMP5 locus), RNA FISH + immunofluorescence colocalization, LC3B puncta and TEM for autophagy flux, in vivo mouse survival","journal":"Experimental hematology & oncology","confidence":"Medium","confidence_rationale":"Tier 1-2 — ChIRP and ChIP establish direct lncRNA-mediated DOT1L recruitment to LAMP5 locus, single lab","pmids":["38374003"],"is_preprint":false},{"year":2025,"finding":"LAMP5 interacts with IRF4 and prevents its degradation through the autophagy-lysosome pathway in multiple myeloma cells. LAMP5 enhances the interaction between IRF4 and the nuclear transport protein KPNA2, facilitating IRF4 nuclear transport and preventing its cytoplasmic retention and subsequent autophagy-lysosome degradation. Nuclear IRF4 promotes c-MYC transcription, and c-MYC positively feeds back to activate LAMP5 transcription. Pyrazofurin disrupts the LAMP5–IRF4 interaction, leading to IRF4 degradation.","method":"Co-immunoprecipitation (LAMP5-IRF4 and IRF4-KPNA2), nuclear/cytoplasmic fractionation, autophagy-lysosome inhibitor experiments, ChIP (IRF4 at c-MYC locus; c-MYC at LAMP5 locus), high-throughput drug screening, in vitro/in vivo myeloma models","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP, fractionation with functional consequences, pathway feedback validated by ChIP, single lab with multiple orthogonal methods","pmids":["40721659"],"is_preprint":false}],"current_model":"LAMP5 is a LAMP-family membrane protein that functions primarily as an endosomal/lysosomal trafficking regulator: in neurons it fine-tunes GABAergic synaptic transmission (without being required for VGAT targeting in mammals); in plasmacytoid dendritic cells and MLL-rearranged leukemia cells it controls the endosomal sorting of TLR9 and innate immune signaling complexes, shifting signal flux between NF-κB- and type I IFN-promoting compartments; and it acts as an autophagic suppressor that protects specific client proteins (MLL fusion oncoproteins, IRF4) from autophagy-lysosome degradation, with its own expression driven by DOT1L-mediated H3K79 methylation at its locus."},"narrative":{"teleology":[{"year":2007,"claim":"The first mechanistic function was established in C. elegans, where UNC-46 (LAMP5 ortholog) was shown to sort the vesicular GABA transporter to synaptic vesicles, revealing a role as a vesicular trafficking factor in GABAergic neurons.","evidence":"Genetic loss-of-function in unc-46 mutants with electrophysiology and fluorescence localization in C. elegans","pmids":["17558401"],"confidence":"High","gaps":["Whether this VGAT-sorting function is conserved in mammals was untested","The molecular mechanism by which UNC-46 recognizes and sorts VGAT was not resolved","Subcellular compartment identity in mammalian neurons was undefined"]},{"year":2007,"claim":"In parallel, LAMP5 was found to define a novel early endocytic compartment in mammalian cortical neurons, distinct from classical lysosomes, recycling to the plasma membrane via dynamin/AP2-dependent endocytosis despite harboring a cryptic lysosomal retention motif.","evidence":"GFP-fusion localization, endocytosis assays, and dynamin/AP2 inhibition in primary neurons and HeLa cells","pmids":["17215451"],"confidence":"Medium","gaps":["The cargo sorted by LAMP5 in this novel compartment was not identified","Functional consequence of LAMP5 endosomal cycling in neurons was not determined"]},{"year":2011,"claim":"Extending beyond neurons, LAMP5 was localized to the ERGIC in human plasmacytoid dendritic cells and shown to be rapidly lost upon TLR activation, establishing its role in innate immune cell biology.","evidence":"Immunofluorescence colocalization with ERGIC markers and flow cytometry in primary human pDCs stimulated with CpG","pmids":["21642595"],"confidence":"Medium","gaps":["The functional consequence of LAMP5 loss upon pDC activation was unknown","Whether LAMP5 directly participates in TLR signaling was untested"]},{"year":2016,"claim":"Mammalian knockout studies resolved a key evolutionary question: LAMP5 modulates GABAergic short-term plasticity and behavior but is not required for VGAT synaptic vesicle targeting, unlike its C. elegans ortholog.","evidence":"LAMP5 knockout mouse with electrophysiology, VGAT immunofluorescence, and behavioral assays","pmids":["27272053"],"confidence":"High","gaps":["The molecular cargo or mechanism by which LAMP5 modulates short-term plasticity remained undefined","Whether LAMP5 sorts other synaptic vesicle proteins in mammals was not addressed"]},{"year":2017,"claim":"The TLR9-sorting function of LAMP5 in pDCs was mechanistically defined: LAMP5 directs TLR9 to LAMP1+ late endosomes promoting NF-κB/TNF, while its silencing retains TLR9 in a VAMP3+/LAMP2+ compartment that enhances type I IFN production.","evidence":"siRNA knockdown in primary human pDCs with TLR9 colocalization, cytokine measurements, and tumor-derived pDC analysis","pmids":["29030552"],"confidence":"High","gaps":["The direct physical interaction between LAMP5 and TLR9 was not demonstrated","Whether LAMP5 sorts other innate receptors beyond TLR9 was not explored"]},{"year":2019,"claim":"LAMP5 was revealed as a transcriptional target of DOT1L and an autophagic suppressor in MLL-rearranged leukemia, protecting MLL fusion oncoproteins from selective autophagic degradation — a function mechanistically distinct from its endosomal sorting role.","evidence":"ChIP for DOT1L at LAMP5 locus, LAMP5 knockdown with autophagy flux assays in leukemia cell lines and in vivo mouse models","pmids":["30651276"],"confidence":"High","gaps":["How LAMP5 physically blocks autophagic recognition of MLL fusion proteins was unknown","Whether the autophagy-suppressive function extends to non-leukemic contexts was untested"]},{"year":2019,"claim":"Brainstem and spinal cord studies confirmed LAMP5 expression at inhibitory synaptic terminals and showed that KO mice display exaggerated startle responses, reinforcing the role in sensorimotor inhibitory processing without VIAAT mislocalization.","evidence":"LAMP5 knockout mouse with auditory brainstem response, startle reflex assays, and VIAAT colocalization","pmids":["30867010"],"confidence":"Medium","gaps":["The vesicular cargo or membrane dynamics regulated by LAMP5 at inhibitory synapses remain unidentified","Circuit-level mechanism linking LAMP5 loss to enhanced startle was not delineated"]},{"year":2022,"claim":"The endosomal signal-switching function of LAMP5 was extended to MLL-rearranged leukemia: LAMP5 transfers innate signaling flux from IFN to NF-κB endosomes downstream of TLR/IL-1R, and IRF7 depletion partially rescues growth inhibition from LAMP5 knockdown, establishing epistasis.","evidence":"LAMP5 knockdown with NF-κB/IFN reporters, IRF7 double-knockdown epistasis, in vivo leukemia model, and surface LAMP5 detection by antibody-drug conjugate","pmids":["33910331"],"confidence":"Medium","gaps":["The physical mechanism of endosomal signal partitioning by LAMP5 in leukemia cells was not resolved","Whether surface LAMP5 has a functional role or is merely a therapeutic target was unclear"]},{"year":2024,"claim":"The transcriptional regulation of LAMP5 was refined: the lncRNA LAMP5-AS1 recruits DOT1L to the LAMP5 locus, establishing a lncRNA-dependent chromatin activation axis that sustains the LAMP5-autophagy suppression circuit in MLL leukemia.","evidence":"ChIRP and ChIP assays for LAMP5-AS1 and DOT1L/H3K79me2 at LAMP5 locus, RNA FISH, autophagy flux by TEM, in vivo mouse survival","pmids":["38374003"],"confidence":"Medium","gaps":["Whether LAMP5-AS1-mediated DOT1L recruitment is the sole mechanism of LAMP5 transcription in non-leukemic contexts is unknown","The stoichiometry and structural basis of LAMP5-AS1–DOT1L interaction were not defined"]},{"year":2025,"claim":"LAMP5's autophagy-suppressive function was shown to extend to multiple myeloma, where LAMP5 binds IRF4, enhances IRF4–KPNA2 interaction for nuclear import, and prevents cytoplasmic IRF4 autophagy-lysosome degradation, establishing a feedforward loop with c-MYC that sustains myeloma cell survival.","evidence":"Reciprocal Co-IP (LAMP5–IRF4, IRF4–KPNA2), nuclear/cytoplasmic fractionation, ChIP at c-MYC and LAMP5 promoters, drug screening identifying pyrazofurin, in vivo myeloma model","pmids":["40721659"],"confidence":"Medium","gaps":["Structural basis of the LAMP5–IRF4 interaction and how pyrazofurin disrupts it is unresolved","Whether LAMP5 protects other transcription factors from autophagy beyond MLL fusions and IRF4 is unknown"]},{"year":null,"claim":"A unifying structural and mechanistic model explaining how LAMP5 simultaneously functions as an endosomal sorting factor and an autophagy suppressor — and whether these are manifestations of a single membrane-trafficking mechanism — remains to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of LAMP5 exists to explain its dual sorting and autophagy-suppressive activities","The direct binding partners on endosomal membranes that mediate TLR9 and signaling complex sorting have not been identified","Whether neuronal and immune functions of LAMP5 share the same molecular mechanism is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,4,10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,5,7]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,4]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,7]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4,7]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5,9,10]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1,4]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[5,7,10]}],"complexes":[],"partners":["VGAT","TLR9","IRF4","KPNA2","ANXA7","DOT1L"],"other_free_text":[]},"mechanistic_narrative":"LAMP5 is a lysosomal-associated membrane protein family member that functions as an endosomal sorting factor controlling vesicular trafficking in neurons, dendritic cells, and hematopoietic malignancies. In neurons, LAMP5 localizes to inhibitory synaptic terminals and modulates GABAergic short-term synaptic plasticity and sensorimotor gating, though unlike its C. elegans ortholog UNC-46, it is dispensable for VGAT trafficking in mammals [PMID:27272053, PMID:30867010]. In plasmacytoid dendritic cells and MLL-rearranged leukemia cells, LAMP5 directs TLR9 and innate signaling complexes toward NF-κB-promoting late endosomes and away from type I interferon-inducing compartments; its depletion shifts signaling toward IFN production [PMID:29030552, PMID:33910331]. LAMP5 also acts as an autophagic suppressor whose transcription is driven by DOT1L-mediated H3K79 methylation, protecting client oncoproteins such as MLL fusions and IRF4 from autophagy-lysosome degradation [PMID:30651276, PMID:40721659]."},"prefetch_data":{"uniprot":{"accession":"Q9UJQ1","full_name":"Lysosome-associated membrane glycoprotein 5","aliases":["Brain and dendritic cell-associated LAMP","Brain-associated LAMP-like protein","BAD-LAMP","Lysosome-associated membrane protein 5","LAMP-5"],"length_aa":280,"mass_kda":31.5,"function":"Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain","subcellular_location":"Cell membrane; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Endoplasmic reticulum-Golgi intermediate compartment membrane; Endosome membrane; Cytoplasmic vesicle membrane; Cell projection, dendrite; Cell projection, growth cone membrane; Early endosome membrane; Recycling endosome","url":"https://www.uniprot.org/uniprotkb/Q9UJQ1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LAMP5","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/LAMP5","total_profiled":1310},"omim":[{"mim_id":"614641","title":"LYSOSOME-ASSOCIATED MEMBRANE PROTEIN 5; LAMP5","url":"https://www.omim.org/entry/614641"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Cytosol","reliability":"Uncertain"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":297.8}],"url":"https://www.proteinatlas.org/search/LAMP5"},"hgnc":{"alias_symbol":["dJ1119D9.3","BAD-LAMP","UNC-46"],"prev_symbol":["C20orf103"]},"alphafold":{"accession":"Q9UJQ1","domains":[{"cath_id":"2.40.160.110","chopping":"31-224","consensus_level":"high","plddt":91.7886,"start":31,"end":224},{"cath_id":"1.20.5","chopping":"226-260","consensus_level":"medium","plddt":93.6057,"start":226,"end":260}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UJQ1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UJQ1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UJQ1-F1-predicted_aligned_error_v6.png","plddt_mean":86.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LAMP5","jax_strain_url":"https://www.jax.org/strain/search?query=LAMP5"},"sequence":{"accession":"Q9UJQ1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UJQ1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UJQ1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UJQ1"}},"corpus_meta":[{"pmid":"29030552","id":"PMC_29030552","title":"BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29030552","citation_count":64,"is_preprint":false},{"pmid":"32552847","id":"PMC_32552847","title":"The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia.","date":"2020","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32552847","citation_count":60,"is_preprint":false},{"pmid":"30651276","id":"PMC_30651276","title":"Activation of the Lysosome-Associated Membrane Protein LAMP5 by DOT1L Serves as a Bodyguard for MLL Fusion Oncoproteins to Evade Degradation in Leukemia.","date":"2019","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/30651276","citation_count":42,"is_preprint":false},{"pmid":"27272053","id":"PMC_27272053","title":"LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27272053","citation_count":38,"is_preprint":false},{"pmid":"17558401","id":"PMC_17558401","title":"UNC-46 is required for trafficking of the vesicular GABA transporter.","date":"2007","source":"Nature neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/17558401","citation_count":38,"is_preprint":false},{"pmid":"21642595","id":"PMC_21642595","title":"BAD-LAMP is a novel biomarker of nonactivated human plasmacytoid dendritic cells.","date":"2011","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/21642595","citation_count":32,"is_preprint":false},{"pmid":"17215451","id":"PMC_17215451","title":"BAD-LAMP defines a subset of early endocytic organelles in subpopulations of cortical projection neurons.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17215451","citation_count":25,"is_preprint":false},{"pmid":"30867010","id":"PMC_30867010","title":"LAMP5 in presynaptic inhibitory terminals in the hindbrain and spinal cord: a role in startle response and auditory processing.","date":"2019","source":"Molecular brain","url":"https://pubmed.ncbi.nlm.nih.gov/30867010","citation_count":17,"is_preprint":false},{"pmid":"37620352","id":"PMC_37620352","title":"Targeting ANXA7/LAMP5-mTOR axis attenuates spinal cord injury by inhibiting neuronal apoptosis via enhancing autophagy in mice.","date":"2023","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/37620352","citation_count":16,"is_preprint":false},{"pmid":"33910331","id":"PMC_33910331","title":"LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for mixed lineage leukemia-rearranged acute leukemia.","date":"2022","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/33910331","citation_count":14,"is_preprint":false},{"pmid":"37033323","id":"PMC_37033323","title":"LAMP5 may promote MM progression by activating p38.","date":"2023","source":"Pathology oncology research : POR","url":"https://pubmed.ncbi.nlm.nih.gov/37033323","citation_count":5,"is_preprint":false},{"pmid":"38374003","id":"PMC_38374003","title":"Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.","date":"2024","source":"Experimental hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38374003","citation_count":3,"is_preprint":false},{"pmid":"40721659","id":"PMC_40721659","title":"LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.","date":"2025","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/40721659","citation_count":2,"is_preprint":false},{"pmid":"39634037","id":"PMC_39634037","title":"LAMP5, One of Four Genes Related to Oxidative Stress That Predict Biochemical Recurrence-Free Survival, Promotes Proliferation and Invasion in Prostate Cancer.","date":"2024","source":"Advances and applications in bioinformatics and chemistry : AABC","url":"https://pubmed.ncbi.nlm.nih.gov/39634037","citation_count":1,"is_preprint":false},{"pmid":"41663867","id":"PMC_41663867","title":"Oncogenic and immunological roles of LAMP5 across cancers and its potential utility in bladder cancer.","date":"2026","source":"Apoptosis : an international journal on programmed cell death","url":"https://pubmed.ncbi.nlm.nih.gov/41663867","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.24.690101","title":"Multiplex imaging combined to machine learning enable automated profiling of cortical 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The transporter recruits UNC-46 to synaptic vesicle precursors in the cell body, and UNC-46 sorts the transporter both at the cell body and during endocytosis at the synapse.\",\n      \"method\": \"Genetic loss-of-function (unc-46 mutants), electrophysiology (miniature currents), fluorescence localization of transporter in axons\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype, electrophysiology, and localization; replicated concept in multiple follow-up studies\",\n      \"pmids\": [\"17558401\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"BAD-LAMP (LAMP5) defines a novel early endocytic compartment in cortical projection neurons distinct from classical lysosomal/endosomal compartments. It is endocytosed and recycles to the plasma membrane through a dynamin/AP2-dependent mechanism. A cryptic lysosomal retention motif in the cytoplasmic tail is actively counteracted by sorting signals that keep LAMP5 away from lysosomes.\",\n      \"method\": \"GFP-fusion protein subcellular localization, endocytosis assay in primary neurons and transfected HeLa cells, dynamin/AP2 inhibition experiments\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment with functional consequence, single lab, multiple methods\",\n      \"pmids\": [\"17215451\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In human plasmacytoid dendritic cells (pDCs), BAD-LAMP (LAMP5) is localized in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and is rapidly lost upon activation by CpG oligonucleotides.\",\n      \"method\": \"Immunofluorescence colocalization with ERGIC markers, flow cytometry on freshly isolated CD123+ pDCs before and after CpG stimulation\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiment in primary human cells with functional context (activation-linked loss)\",\n      \"pmids\": [\"21642595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"In the mouse brain, LAMP5 is expressed in subpopulations of GABAergic forebrain neurons and is present at synaptic terminals overlapping with VGAT. LAMP5-deficient mice show altered short-term synaptic plasticity in GABAergic transmission, decreased anxiety, and deficits in olfactory discrimination, but VGAT localization is unaffected, indicating LAMP5 is not required for VGAT trafficking in mammals (unlike its C. elegans ortholog UNC-46).\",\n      \"method\": \"LAMP5 knockout mouse, electrophysiology (short-term plasticity), immunofluorescence colocalization with VGAT, behavioral assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined electrophysiological and behavioral phenotypes, multiple orthogonal methods\",\n      \"pmids\": [\"27272053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in human pDCs, promoting NF-κB activation and TNF production upon DNA detection. BAD-LAMP silencing enhances TLR9 retention in an inducible VAMP3+/LAMP2+/LAMP1- endolysosomal compartment, increasing type I interferon (IFN) signaling. Sustained BAD-LAMP expression thus limits type I IFN production by sorting TLR9 to late endosomes away from the IFN-promoting compartment.\",\n      \"method\": \"siRNA silencing of LAMP5 in primary human pDCs, TLR9 colocalization by immunofluorescence, cytokine measurement (IFN, TNF), TGF-β treatment and tumor-derived pDC analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KD with defined molecular and functional readouts in primary human cells, multiple orthogonal approaches, replicated in tumor microenvironment context\",\n      \"pmids\": [\"29030552\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"LAMP5 is a direct transcriptional target of DOT1L (H3K79 histone methyltransferase) in MLL leukemia and functions as an autophagic suppressor that protects MLL fusion proteins from autophagic degradation. Knockdown of LAMP5 promotes selective autophagic degradation of MLL oncoproteins.\",\n      \"method\": \"ChIP (DOT1L at LAMP5 locus), LAMP5 knockdown in leukemia cell lines and primary cells, autophagy flux assays (LC3, autophagic degradation), DOT1L inhibitor treatment, in vivo mouse leukemia model\",\n      \"journal\": \"Clinical cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — ChIP establishes direct transcriptional regulation, KD with defined autophagic phenotype confirmed in vitro and in vivo\",\n      \"pmids\": [\"30651276\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"LAMP5 is expressed exclusively in inhibitory (GABAergic/glycinergic) synaptic terminals in the brainstem and spinal cord. LAMP5 knockout mice show increased auditory and tactile startle responses and larger auditory brainstem response wave amplitudes, consistent with a role in sensorimotor inhibitory processing. VIAAT localization is unaffected in LAMP5 KO, confirming no conserved role in VIAAT trafficking.\",\n      \"method\": \"Lamp5 knockout mouse, auditory brainstem response (ABR) recording, acoustic and tactile startle reflex assays, immunofluorescence colocalization with VIAAT\",\n      \"journal\": \"Molecular brain\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined electrophysiological and behavioral phenotype, single lab\",\n      \"pmids\": [\"30867010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LAMP5 modulates innate immune signaling in MLL-rearranged leukemia by transferring signal flux from interferon signaling endosomes to pro-inflammatory signaling endosomes. LAMP5 depletion inhibits NF-κB signaling and increases type I interferon signaling downstream of TLR/IL-1R activation. IRF7 depletion partially rescues the growth inhibition caused by LAMP5 knockdown (epistasis). LAMP5 is also detectable on the cell surface of MLL-r leukemia cells.\",\n      \"method\": \"LAMP5 knockdown in MLL-r leukemia cell lines, NF-κB and IFN pathway reporter assays, IRF7 double-knockdown epistasis, in vivo leukemia model, antibody-drug conjugate targeting surface LAMP5\",\n      \"journal\": \"Haematologica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with pathway-level readouts and epistasis, single lab with multiple complementary methods\",\n      \"pmids\": [\"33910331\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"LAMP5 interacts with ANXA7, and this interaction is disrupted by an Asp411 mutation in ANXA7. LAMP5 overexpression stabilizes lysosomal acidic environment and promotes autophagy flux, counteracting the effects of ANXA7 downregulation on autophagy inhibition and apoptosis activation after OGD/R injury in neurons. ANXA7 activation stabilizes LAMP5 protein expression.\",\n      \"method\": \"Co-immunoprecipitation (ANXA7-LAMP5 interaction), Asp411 mutation analysis, LAMP5 overexpression in OGD/R neuronal model, lysosomal acidification assay, autophagy flux assay, apoptosis assay\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP establishes interaction, overexpression with functional readouts, single lab\",\n      \"pmids\": [\"37620352\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LAMP5-AS1 lncRNA recruits the H3K79 histone methyltransferase DOT1L to the LAMP5 locus, directly activating LAMP5 transcription. Blocking the LAMP5-AS1–LAMP5 axis enhances autophagic degradation of MLL fusion proteins.\",\n      \"method\": \"ChIRP assay (LAMP5-AS1 at LAMP5 locus), ChIP (DOT1L/H3K79me2 at LAMP5 locus), RNA FISH + immunofluorescence colocalization, LC3B puncta and TEM for autophagy flux, in vivo mouse survival\",\n      \"journal\": \"Experimental hematology & oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — ChIRP and ChIP establish direct lncRNA-mediated DOT1L recruitment to LAMP5 locus, single lab\",\n      \"pmids\": [\"38374003\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"LAMP5 interacts with IRF4 and prevents its degradation through the autophagy-lysosome pathway in multiple myeloma cells. LAMP5 enhances the interaction between IRF4 and the nuclear transport protein KPNA2, facilitating IRF4 nuclear transport and preventing its cytoplasmic retention and subsequent autophagy-lysosome degradation. Nuclear IRF4 promotes c-MYC transcription, and c-MYC positively feeds back to activate LAMP5 transcription. Pyrazofurin disrupts the LAMP5–IRF4 interaction, leading to IRF4 degradation.\",\n      \"method\": \"Co-immunoprecipitation (LAMP5-IRF4 and IRF4-KPNA2), nuclear/cytoplasmic fractionation, autophagy-lysosome inhibitor experiments, ChIP (IRF4 at c-MYC locus; c-MYC at LAMP5 locus), high-throughput drug screening, in vitro/in vivo myeloma models\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, fractionation with functional consequences, pathway feedback validated by ChIP, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"40721659\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LAMP5 is a LAMP-family membrane protein that functions primarily as an endosomal/lysosomal trafficking regulator: in neurons it fine-tunes GABAergic synaptic transmission (without being required for VGAT targeting in mammals); in plasmacytoid dendritic cells and MLL-rearranged leukemia cells it controls the endosomal sorting of TLR9 and innate immune signaling complexes, shifting signal flux between NF-κB- and type I IFN-promoting compartments; and it acts as an autophagic suppressor that protects specific client proteins (MLL fusion oncoproteins, IRF4) from autophagy-lysosome degradation, with its own expression driven by DOT1L-mediated H3K79 methylation at its locus.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"LAMP5 is a lysosomal-associated membrane protein family member that functions as an endosomal sorting factor controlling vesicular trafficking in neurons, dendritic cells, and hematopoietic malignancies. In neurons, LAMP5 localizes to inhibitory synaptic terminals and modulates GABAergic short-term synaptic plasticity and sensorimotor gating, though unlike its C. elegans ortholog UNC-46, it is dispensable for VGAT trafficking in mammals [PMID:27272053, PMID:30867010]. In plasmacytoid dendritic cells and MLL-rearranged leukemia cells, LAMP5 directs TLR9 and innate signaling complexes toward NF-κB-promoting late endosomes and away from type I interferon-inducing compartments; its depletion shifts signaling toward IFN production [PMID:29030552, PMID:33910331]. LAMP5 also acts as an autophagic suppressor whose transcription is driven by DOT1L-mediated H3K79 methylation, protecting client oncoproteins such as MLL fusions and IRF4 from autophagy-lysosome degradation [PMID:30651276, PMID:40721659].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"The first mechanistic function was established in C. elegans, where UNC-46 (LAMP5 ortholog) was shown to sort the vesicular GABA transporter to synaptic vesicles, revealing a role as a vesicular trafficking factor in GABAergic neurons.\",\n      \"evidence\": \"Genetic loss-of-function in unc-46 mutants with electrophysiology and fluorescence localization in C. elegans\",\n      \"pmids\": [\"17558401\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether this VGAT-sorting function is conserved in mammals was untested\",\n        \"The molecular mechanism by which UNC-46 recognizes and sorts VGAT was not resolved\",\n        \"Subcellular compartment identity in mammalian neurons was undefined\"\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"In parallel, LAMP5 was found to define a novel early endocytic compartment in mammalian cortical neurons, distinct from classical lysosomes, recycling to the plasma membrane via dynamin/AP2-dependent endocytosis despite harboring a cryptic lysosomal retention motif.\",\n      \"evidence\": \"GFP-fusion localization, endocytosis assays, and dynamin/AP2 inhibition in primary neurons and HeLa cells\",\n      \"pmids\": [\"17215451\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The cargo sorted by LAMP5 in this novel compartment was not identified\",\n        \"Functional consequence of LAMP5 endosomal cycling in neurons was not determined\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extending beyond neurons, LAMP5 was localized to the ERGIC in human plasmacytoid dendritic cells and shown to be rapidly lost upon TLR activation, establishing its role in innate immune cell biology.\",\n      \"evidence\": \"Immunofluorescence colocalization with ERGIC markers and flow cytometry in primary human pDCs stimulated with CpG\",\n      \"pmids\": [\"21642595\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The functional consequence of LAMP5 loss upon pDC activation was unknown\",\n        \"Whether LAMP5 directly participates in TLR signaling was untested\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Mammalian knockout studies resolved a key evolutionary question: LAMP5 modulates GABAergic short-term plasticity and behavior but is not required for VGAT synaptic vesicle targeting, unlike its C. elegans ortholog.\",\n      \"evidence\": \"LAMP5 knockout mouse with electrophysiology, VGAT immunofluorescence, and behavioral assays\",\n      \"pmids\": [\"27272053\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular cargo or mechanism by which LAMP5 modulates short-term plasticity remained undefined\",\n        \"Whether LAMP5 sorts other synaptic vesicle proteins in mammals was not addressed\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The TLR9-sorting function of LAMP5 in pDCs was mechanistically defined: LAMP5 directs TLR9 to LAMP1+ late endosomes promoting NF-κB/TNF, while its silencing retains TLR9 in a VAMP3+/LAMP2+ compartment that enhances type I IFN production.\",\n      \"evidence\": \"siRNA knockdown in primary human pDCs with TLR9 colocalization, cytokine measurements, and tumor-derived pDC analysis\",\n      \"pmids\": [\"29030552\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The direct physical interaction between LAMP5 and TLR9 was not demonstrated\",\n        \"Whether LAMP5 sorts other innate receptors beyond TLR9 was not explored\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"LAMP5 was revealed as a transcriptional target of DOT1L and an autophagic suppressor in MLL-rearranged leukemia, protecting MLL fusion oncoproteins from selective autophagic degradation — a function mechanistically distinct from its endosomal sorting role.\",\n      \"evidence\": \"ChIP for DOT1L at LAMP5 locus, LAMP5 knockdown with autophagy flux assays in leukemia cell lines and in vivo mouse models\",\n      \"pmids\": [\"30651276\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How LAMP5 physically blocks autophagic recognition of MLL fusion proteins was unknown\",\n        \"Whether the autophagy-suppressive function extends to non-leukemic contexts was untested\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Brainstem and spinal cord studies confirmed LAMP5 expression at inhibitory synaptic terminals and showed that KO mice display exaggerated startle responses, reinforcing the role in sensorimotor inhibitory processing without VIAAT mislocalization.\",\n      \"evidence\": \"LAMP5 knockout mouse with auditory brainstem response, startle reflex assays, and VIAAT colocalization\",\n      \"pmids\": [\"30867010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The vesicular cargo or membrane dynamics regulated by LAMP5 at inhibitory synapses remain unidentified\",\n        \"Circuit-level mechanism linking LAMP5 loss to enhanced startle was not delineated\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The endosomal signal-switching function of LAMP5 was extended to MLL-rearranged leukemia: LAMP5 transfers innate signaling flux from IFN to NF-κB endosomes downstream of TLR/IL-1R, and IRF7 depletion partially rescues growth inhibition from LAMP5 knockdown, establishing epistasis.\",\n      \"evidence\": \"LAMP5 knockdown with NF-κB/IFN reporters, IRF7 double-knockdown epistasis, in vivo leukemia model, and surface LAMP5 detection by antibody-drug conjugate\",\n      \"pmids\": [\"33910331\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The physical mechanism of endosomal signal partitioning by LAMP5 in leukemia cells was not resolved\",\n        \"Whether surface LAMP5 has a functional role or is merely a therapeutic target was unclear\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The transcriptional regulation of LAMP5 was refined: the lncRNA LAMP5-AS1 recruits DOT1L to the LAMP5 locus, establishing a lncRNA-dependent chromatin activation axis that sustains the LAMP5-autophagy suppression circuit in MLL leukemia.\",\n      \"evidence\": \"ChIRP and ChIP assays for LAMP5-AS1 and DOT1L/H3K79me2 at LAMP5 locus, RNA FISH, autophagy flux by TEM, in vivo mouse survival\",\n      \"pmids\": [\"38374003\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether LAMP5-AS1-mediated DOT1L recruitment is the sole mechanism of LAMP5 transcription in non-leukemic contexts is unknown\",\n        \"The stoichiometry and structural basis of LAMP5-AS1–DOT1L interaction were not defined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"LAMP5's autophagy-suppressive function was shown to extend to multiple myeloma, where LAMP5 binds IRF4, enhances IRF4–KPNA2 interaction for nuclear import, and prevents cytoplasmic IRF4 autophagy-lysosome degradation, establishing a feedforward loop with c-MYC that sustains myeloma cell survival.\",\n      \"evidence\": \"Reciprocal Co-IP (LAMP5–IRF4, IRF4–KPNA2), nuclear/cytoplasmic fractionation, ChIP at c-MYC and LAMP5 promoters, drug screening identifying pyrazofurin, in vivo myeloma model\",\n      \"pmids\": [\"40721659\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of the LAMP5–IRF4 interaction and how pyrazofurin disrupts it is unresolved\",\n        \"Whether LAMP5 protects other transcription factors from autophagy beyond MLL fusions and IRF4 is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and mechanistic model explaining how LAMP5 simultaneously functions as an endosomal sorting factor and an autophagy suppressor — and whether these are manifestations of a single membrane-trafficking mechanism — remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of LAMP5 exists to explain its dual sorting and autophagy-suppressive activities\",\n        \"The direct binding partners on endosomal membranes that mediate TLR9 and signaling complex sorting have not been identified\",\n        \"Whether neuronal and immune functions of LAMP5 share the same molecular mechanism is untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 4, 10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 5, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4, 7]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5, 9, 10]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [5, 7, 10]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"VGAT\",\n      \"TLR9\",\n      \"IRF4\",\n      \"KPNA2\",\n      \"ANXA7\",\n      \"DOT1L\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}