{"gene":"VPS11","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":1990,"finding":"PEP5/VPS11 (Saccharomyces cerevisiae) encodes a 117 kDa peripheral vacuolar membrane protein required for vacuolar biogenesis; pep5 deletion mutants accumulate inactive precursors of vacuolar hydrolases (PrA, PrB, CpY, alkaline phosphatase) and display vestigial vacuole morphology, establishing VPS11 as essential for protein delivery to the vacuole.","method":"Genetic complementation, gene deletion/disruption, cell fractionation, immunoblot with anti-PEP5 fusion protein antibody","journal":"Genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean gene deletion with defined enzymatic phenotype, cell fractionation establishing membrane localization, multiple orthogonal methods, foundational yeast study","pmids":["2204580"],"is_preprint":false},{"year":1998,"finding":"Genetic epistasis in S. cerevisiae shows that the vps8-200 allele partially suppresses the vestigial vacuole phenotype and vacuolar hydrolase processing defect of pep5 (VPS11) mutants, indicating VPS11/Pep5p functions at multiple steps in vacuolar trafficking, including at the Golgi-to-prevacuolar compartment step where Vps8p acts.","method":"Genetic epistasis (double-mutant analysis), vacuolar hydrolase activity assays, vacuolar morphology assessment","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with functional readouts, single lab, two orthogonal methods","pmids":["9475722"],"is_preprint":false},{"year":2003,"finding":"C. albicans VPS11 is required for vacuolar biogenesis, secreted lipase and aspartyl protease activities, and yeast-to-hypha morphogenesis; vps11Δ mutants lack a vacuolar compartment and show delayed germ tube emergence and inability to form mature hyphae, indicating VPS11-mediated trafficking is necessary for hyphal growth.","method":"Gene deletion, vacuolar morphology assay, enzyme activity assays, morphogenesis induction assay","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean gene deletion with multiple defined phenotypic readouts across orthogonal assays in a fungal model","pmids":["12796286"],"is_preprint":false},{"year":2011,"finding":"Loss of Vps11 in zebrafish (platinum mutant, single-nucleotide insertion in vps11) does not block melanophore development, migration, or dispersion, but is essential for melanosome maturation and healthy maintenance of the RPE and photoreceptors, demonstrating a specific role for Vps11 in late organelle biogenesis rather than cell fate.","method":"Bulked segregant analysis, candidate gene sequencing, phenocopy and rescue experiments, RT-PCR, in situ hybridization, histology, immunohistochemistry, transmission electron microscopy","journal":"Investigative ophthalmology & visual science","confidence":"High","confidence_rationale":"Tier 2 / Strong — identified causative mutation, phenocopy and rescue experiments, multiple orthogonal morphological methods","pmids":["21330665"],"is_preprint":false},{"year":2013,"finding":"In zebrafish vps11(w66) mutants, loss of Vps11 leads to caspase-independent chromatophore death associated with increased cathepsin activity; inhibition of cathepsins/calpain (ALLM) or vacuolar H+-ATPase (Bafilomycin A1) restores normal melanophore morphology and number, and LC3B-II accumulation indicates impaired autophagic flux. This establishes Vps11 as promoting melanophore survival by inhibiting cathepsin release/activity.","method":"Zebrafish mutant analysis, TUNEL assay, caspase inhibitor treatment, Western blot for PARP-1 cleavage and LC3B-II, pharmacological inhibition (ALLM, Bafilomycin A1)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (genetic, pharmacological, biochemical), single lab","pmids":["23724125"],"is_preprint":false},{"year":2015,"finding":"T. gondii Vps11 orthologue (TgVps11) is a dynamic protein that associates with Golgi endosomal-related compartments, the vacuole, and immature apical secretory organelles; conditional knockdown of TgVps11 disrupts biogenesis or proper subcellular localization of dense granules, rhoptries, and micronemes, impairing parasite motility, invasion, egress, and intracellular growth.","method":"Conditional knockdown, immunofluorescence/subcellular localization, invasion and motility assays, phenotypic analysis of secretory organelle biogenesis","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knockdown with multiple orthogonal functional readouts confirming essential role in organelle biogenesis","pmids":["25640905"],"is_preprint":false},{"year":2015,"finding":"The VPS11 p.Cys846Gly mutation (homologous yeast mutation tested in Mup1-GFP transport assay) causes moderate impairment of fusion of the late endosome to the vacuole, establishing that the C846G variant specifically disrupts the endosomal-vacuolar fusion step.","method":"Yeast Mup1-GFP transport assay (functional homologue assay), exome analysis, homozygosity mapping","journal":"Journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional transport assay in yeast model, single lab","pmids":["26307567"],"is_preprint":false},{"year":2016,"finding":"The VPS11 C846G (c.2536T>G) missense mutation in humans causes aberrant ubiquitination and accelerated turnover of VPS11 protein, compromised VPS11-VPS18 complex assembly, and impaired autophagic activity; zebrafish with truncated RING-H2 domain show significant reduction in CNS myelination and extensive neuronal death in hindbrain and midbrain.","method":"Whole exome sequencing, ubiquitination assays, VPS11-VPS18 co-immunoprecipitation, autophagy flux assays in human cells, zebrafish genetic model with histology","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP for complex assembly, ubiquitination assay, autophagy assay, in vivo zebrafish model), single paper with rigorous controls","pmids":["27120463"],"is_preprint":false},{"year":2019,"finding":"Vps11 and Vps18, as common subunits of HOPS/CORVET complexes, function as E3 ubiquitin ligases; overexpression of Vps11/Vps18 perturbs ubiquitination in signal transduction pathways including Wnt, estrogen receptor α (ERα), and NFκB; specifically, Vps11/18-mediated ubiquitination of the scaffold protein PELP1 impairs activation of ERα by c-Src.","method":"Overexpression, ubiquitination assays, signaling pathway readouts (Wnt, ERα, NFκB), co-immunoprecipitation for PELP1 ubiquitination","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — E3 ligase activity demonstrated by ubiquitination assays with specific substrate (PELP1) identified, single lab but multiple pathways tested","pmids":["31015428"],"is_preprint":false},{"year":2021,"finding":"VPS11 is strongly expressed in mouse oligodendrocytes and specifically localizes with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin; Vps11 co-localizes with PDGFRα in round vesicles of OPCs/oligodendrocytes in vitro and in vivo, suggesting a role in retrograde endolysosomal transport from the myelin inner tongue to the oligodendrocyte perikaryon.","method":"Immunocytochemistry, immunofluorescent co-staining with MAG, MBP, neurofilament, and PDGFRα markers, in vitro and in vivo co-localization","journal":"ASN neuro","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiments with multiple co-markers, single lab, no functional perturbation experiment","pmids":["33874780"],"is_preprint":false},{"year":2021,"finding":"A novel homozygous VPS11 variant causes adult-onset generalized dystonia; functional studies on patient-derived fibroblasts show marked lysosomal and autophagic abnormalities that are rescued by overexpression of wild-type VPS11, establishing the autophagic-lysosomal pathway as the mechanistic basis of VPS11-related disease.","method":"Patient fibroblast functional studies (lysosomal/autophagic assays), wild-type VPS11 rescue experiment","journal":"Annals of neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional rescue experiment with defined autophagy/lysosomal readouts, single lab","pmids":["33452836"],"is_preprint":false},{"year":2014,"finding":"Knockdown of Vps11 in human cells increases retrograde Golgi transport of Shiga toxin (Stx) and ricin, and also increases Stx toxicity and ricin toxicity; Vps11 knockdown also restores reduced Gb3 (globotriaosylceramide) glycolipid levels caused by moesin depletion, establishing that Vps11 regulates retrograde toxin transport and glycolipid degradation.","method":"siRNA knockdown, Shiga toxin and ricin retrograde transport assays, toxicity assays, Gb3 level measurement","journal":"Communicative & integrative biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (knockdown + trafficking readout), brief communication","pmids":["24778763"],"is_preprint":false},{"year":2024,"finding":"ALKBH5, an m6A RNA demethylase, alleviates hepatic lipid deposition by removing m6A modification on VPS11 mRNA to promote its translation; overexpression of VPS11 reverses FFA-induced lipid accumulation in ALKBH5-silenced hepatocytes by restoring autophagosome-lysosome fusion (autophagic flux).","method":"Overexpression and knockdown of ALKBH5, methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), RNA-seq, VPS11 overexpression rescue, autophagy flux assays (LC3B, p62/SQSTM1), lipid accumulation assays","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — m6A modification mapped on VPS11 mRNA by MeRIP, functional rescue by VPS11 overexpression, multiple orthogonal methods, single lab","pmids":["39434426"],"is_preprint":false},{"year":2022,"finding":"miR-542-3p targets the 3' UTR of human VPS11 mRNA (seed sequence absent in mice/rats), reducing VPS11 expression in macrophages infected with M. tuberculosis; VPS11 overexpression antagonizes the miR-542-3p-mediated promotion of M. tuberculosis survival by restoring autophagic flux, establishing VPS11 as a key autophagy regulator in anti-mycobacterial defense.","method":"Luciferase reporter assay, RNA pulldown, RNA immunoprecipitation, VPS11 overexpression in macrophages, M. tuberculosis survival assay, autophagy flux assays","journal":"Microbial pathogenesis","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct miRNA target validation by luciferase reporter and RNA pulldown, functional rescue experiment, single lab","pmids":["35662671"],"is_preprint":false}],"current_model":"VPS11 is a core structural subunit of the HOPS and CORVET endolysosomal tethering complexes that functions as an E3 ubiquitin ligase and is essential for vacuolar/lysosomal biogenesis, late endosome-to-lysosome fusion, autophagic flux, and melanosome maturation; disease-causing mutations (notably p.Cys846Gly in the RING-H2 domain) disrupt VPS11-VPS18 complex assembly, cause aberrant ubiquitination and accelerated VPS11 turnover, impair autophagosome-lysosome fusion, and in vivo lead to hypomyelination, neurodegeneration, and lysosomal storage, while VPS11 expression is post-transcriptionally regulated by m6A demethylation of its mRNA by ALKBH5."},"narrative":{"mechanistic_narrative":"VPS11 is a core subunit of the endolysosomal/vacuolar tethering machinery that drives delivery of proteins to the vacuole/lysosome and the maturation of late organelles across eukaryotes [PMID:2204580, PMID:12796286]. First defined in yeast as a peripheral vacuolar membrane protein essential for vacuolar biogenesis and the proteolytic maturation of vacuolar hydrolases [PMID:2204580], it acts at multiple trafficking steps including the Golgi-to-prevacuolar route and, critically, the fusion of late endosomes with the vacuole/lysosome [PMID:9475722, PMID:26307567]. As a shared subunit of the HOPS/CORVET complexes it carries E3 ubiquitin ligase activity, ubiquitinating substrates such as the scaffold PELP1 to modulate ERα, Wnt, and NFκB signaling [PMID:31015428]. Across organisms VPS11 is required for late organelle biogenesis rather than cell fate: melanosome maturation and RPE/photoreceptor maintenance in zebrafish [PMID:21330665], and biogenesis of secretory organelles (dense granules, rhoptries, micronemes) in Toxoplasma [PMID:25640905]. A central downstream function is the support of autophagic flux through autophagosome-lysosome fusion [PMID:27120463, PMID:33452836]. The human VPS11 C846G mutation in the RING-H2 domain causes aberrant ubiquitination and accelerated turnover of VPS11, compromised VPS11-VPS18 complex assembly, and impaired autophagy, producing CNS hypomyelination and neuronal death; other homozygous variants cause adult-onset generalized dystonia, with patient-fibroblast lysosomal and autophagic defects rescued by wild-type VPS11 [PMID:27120463, PMID:33452836]. VPS11 expression is post-transcriptionally tuned: ALKBH5-mediated m6A demethylation of VPS11 mRNA promotes its translation [PMID:39434426], and miR-542-3p targets its 3' UTR to suppress autophagy-dependent anti-mycobacterial defense [PMID:35662671].","teleology":[{"year":1990,"claim":"Established that VPS11 is required for biogenesis of the vacuole and delivery/maturation of vacuolar hydrolases, defining its foundational role in endolysosomal trafficking.","evidence":"Gene deletion, cell fractionation, and immunoblot of vacuolar hydrolase precursors in S. cerevisiae","pmids":["2204580"],"confidence":"High","gaps":["Did not define the molecular complex or tethering mechanism","No mammalian ortholog characterized"]},{"year":1998,"claim":"Showed VPS11 acts at multiple trafficking steps, including the Golgi-to-prevacuolar step where Vps8p operates, refining where in the pathway it functions.","evidence":"Genetic epistasis (vps8/pep5 double mutants) with vacuolar hydrolase and morphology readouts in yeast","pmids":["9475722"],"confidence":"Medium","gaps":["Genetic suppression does not establish direct physical interaction","Step-specific molecular role unresolved"]},{"year":2003,"claim":"Extended VPS11 function to fungal organelle biogenesis and linked vacuolar trafficking to hyphal morphogenesis and secreted enzyme activity.","evidence":"Gene deletion with vacuolar morphology, enzyme activity, and morphogenesis assays in C. albicans","pmids":["12796286"],"confidence":"High","gaps":["Link between trafficking defect and morphogenesis mechanistically indirect"]},{"year":2011,"claim":"Demonstrated VPS11 is dispensable for cell fate but essential for late organelle maturation, distinguishing a biogenesis role from a developmental one.","evidence":"Zebrafish platinum mutant with phenocopy/rescue, histology, and electron microscopy of melanosomes, RPE, and photoreceptors","pmids":["21330665"],"confidence":"High","gaps":["Molecular basis of melanosome maturation defect not defined"]},{"year":2013,"claim":"Connected VPS11 loss to impaired autophagic flux and cathepsin-driven cell death, implicating the lysosomal degradation pathway in VPS11 phenotypes.","evidence":"Zebrafish mutant with TUNEL, LC3B-II Western blot, and pharmacological inhibition of cathepsins/calpain and V-ATPase","pmids":["23724125"],"confidence":"Medium","gaps":["Causal chain from autophagy block to cathepsin release inferred pharmacologically","Single lab"]},{"year":2015,"claim":"Pinpointed the disease C846G variant to the late endosome-to-vacuole fusion step using a functional homolog assay, mechanistically localizing the defect.","evidence":"Yeast Mup1-GFP transport assay of the homologous mutation, plus exome and homozygosity mapping","pmids":["26307567"],"confidence":"Medium","gaps":["Assay in yeast surrogate, not human cells","Impairment characterized as moderate"]},{"year":2015,"claim":"Showed VPS11 supports secretory organelle biogenesis and parasite infectivity, broadening its organelle-maturation role to apicomplexan secretory pathways.","evidence":"Conditional knockdown with immunofluorescence localization and invasion/motility/egress assays in T. gondii","pmids":["25640905"],"confidence":"High","gaps":["Direct tethering partners in the parasite not identified"]},{"year":2016,"claim":"Defined the molecular consequences of the human C846G RING-H2 mutation, linking disrupted VPS11-VPS18 assembly and aberrant ubiquitination to impaired autophagy and CNS hypomyelination.","evidence":"Whole exome sequencing, ubiquitination and Co-IP assays, autophagy flux assays in human cells, and zebrafish RING-H2 truncation model","pmids":["27120463"],"confidence":"High","gaps":["Structural basis of complex destabilization not resolved","E3 ligase activity not directly addressed here"]},{"year":2019,"claim":"Identified VPS11/VPS18 as functional E3 ubiquitin ligases acting on signaling substrates, expanding VPS11 beyond membrane tethering into signal-pathway regulation.","evidence":"Overexpression and ubiquitination assays across Wnt/ERα/NFκB pathways with Co-IP of PELP1 ubiquitination","pmids":["31015428"],"confidence":"Medium","gaps":["Demonstrated by overexpression; physiological context unclear","Direct catalytic mechanism not reconstituted"]},{"year":2021,"claim":"Localized VPS11 to oligodendrocyte myelin and endolysosomal vesicles, providing a cellular basis for VPS11-related hypomyelination.","evidence":"Immunocytochemistry and co-staining with MAG, MBP, PDGFRα in mouse oligodendrocytes in vitro and in vivo","pmids":["33874780"],"confidence":"Medium","gaps":["No functional perturbation experiment","Retrograde transport role inferred from co-localization"]},{"year":2021,"claim":"Linked a distinct VPS11 variant to adult-onset dystonia and established the autophagic-lysosomal pathway as the disease mechanism via rescue.","evidence":"Patient fibroblast lysosomal/autophagic assays rescued by wild-type VPS11 overexpression","pmids":["33452836"],"confidence":"Medium","gaps":["Single family/lab","Genotype-phenotype relationship to other VPS11 variants not resolved"]},{"year":2022,"claim":"Showed VPS11 is a post-transcriptionally regulated autophagy effector in anti-mycobacterial immunity, with miR-542-3p suppressing it to favor pathogen survival.","evidence":"Luciferase reporter, RNA pulldown/IP, VPS11 overexpression rescue, and M. tuberculosis survival/autophagy assays in macrophages","pmids":["35662671"],"confidence":"Medium","gaps":["miR target site human-specific","Single lab"]},{"year":2024,"claim":"Identified m6A demethylation by ALKBH5 as a translational control mechanism for VPS11, linking VPS11-dependent autophagic flux to hepatic lipid homeostasis.","evidence":"ALKBH5 manipulation, MeRIP-qPCR on VPS11 mRNA, VPS11 overexpression rescue, and autophagy/lipid assays in hepatocytes","pmids":["39434426"],"confidence":"Medium","gaps":["Reader protein decoding the m6A mark not identified","Single lab"]},{"year":null,"claim":"How VPS11's tethering, E3 ligase, and complex-assembly functions are mechanistically integrated, and the structural basis by which disease mutations destabilize the HOPS/CORVET core, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of VPS11 within HOPS/CORVET","Catalytic E3 mechanism not reconstituted in vitro","Relationship between ubiquitin ligase activity and membrane tethering unclear"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[8]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,7]}],"localization":[{"term_id":"GO:0005773","term_label":"vacuole","supporting_discovery_ids":[0]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[6,9]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[10]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[5,11]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7,10,13]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,6,11]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[3,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[8]}],"complexes":["HOPS","CORVET"],"partners":["VPS18","VPS8","PELP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H270","full_name":"Vacuolar protein sorting-associated protein 11 homolog","aliases":["RING finger protein 108"],"length_aa":941,"mass_kda":107.8,"function":"Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in cargo transport from early to late endosomes and required for the transition from early to late endosomes (PubMed:21148287). Involved in the retrograde Shiga toxin transport (PubMed:23593995)","subcellular_location":"Endosome; Late endosome membrane; Lysosome membrane; Early endosome; Cytoplasmic vesicle; Cytoplasmic vesicle, autophagosome; Cytoplasmic vesicle, clathrin-coated vesicle","url":"https://www.uniprot.org/uniprotkb/Q9H270/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VPS11","classification":"Not Classified","n_dependent_lines":20,"n_total_lines":74,"dependency_fraction":0.2702702702702703},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"VPS18","stoichiometry":10.0},{"gene":"TGFBRAP1","stoichiometry":4.0},{"gene":"VPS16","stoichiometry":0.2},{"gene":"VPS33A","stoichiometry":0.2},{"gene":"VPS8","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/VPS11","total_profiled":1310},"omim":[{"mim_id":"619637","title":"DYSTONIA 32; DYT32","url":"https://www.omim.org/entry/619637"},{"mim_id":"616694","title":"ECM29 PROTEASOME ADAPTOR AND SCAFFOLD PROTEIN; ECPAS","url":"https://www.omim.org/entry/616694"},{"mim_id":"616683","title":"LEUKODYSTROPHY, HYPOMYELINATING, 12; HLD12","url":"https://www.omim.org/entry/616683"},{"mim_id":"610034","title":"VPS33A CORE SUBUNIT OF CORVET AND HOPS COMPLEXES; VPS33A","url":"https://www.omim.org/entry/610034"},{"mim_id":"608552","title":"VPS33B LATE ENDOSOME AND LYSOSOME ASSOCIATED; VPS33B","url":"https://www.omim.org/entry/608552"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/VPS11"},"hgnc":{"alias_symbol":["RNF108","PEP5"],"prev_symbol":[]},"alphafold":{"accession":"Q9H270","domains":[{"cath_id":"1.25.40","chopping":"688-767","consensus_level":"high","plddt":71.9149,"start":688,"end":767}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H270","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H270-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H270-F1-predicted_aligned_error_v6.png","plddt_mean":78.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VPS11","jax_strain_url":"https://www.jax.org/strain/search?query=VPS11"},"sequence":{"accession":"Q9H270","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H270.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H270/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H270"}},"corpus_meta":[{"pmid":"7556197","id":"PMC_7556197","title":"Nucleotide sequence of the lantibiotic Pep5 biosynthetic gene cluster and functional analysis of PepP and PepC. 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Isolation and characterization of a prepeptide containing dehydroamino acids.","date":"1990","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2253617","citation_count":80,"is_preprint":false},{"pmid":"27120463","id":"PMC_27120463","title":"A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.","date":"2016","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27120463","citation_count":61,"is_preprint":false},{"pmid":"12796286","id":"PMC_12796286","title":"Candida albicans VPS11 is required for vacuole biogenesis and germ tube formation.","date":"2003","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/12796286","citation_count":59,"is_preprint":false},{"pmid":"8775972","id":"PMC_8775972","title":"The biosynthesis of the lantibiotics epidermin, gallidermin, Pep5 and epilancin K7.","date":"1996","source":"Antonie van 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delivery to the vacuole.\",\n      \"method\": \"Genetic complementation, gene deletion/disruption, cell fractionation, immunoblot with anti-PEP5 fusion protein antibody\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean gene deletion with defined enzymatic phenotype, cell fractionation establishing membrane localization, multiple orthogonal methods, foundational yeast study\",\n      \"pmids\": [\"2204580\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Genetic epistasis in S. cerevisiae shows that the vps8-200 allele partially suppresses the vestigial vacuole phenotype and vacuolar hydrolase processing defect of pep5 (VPS11) mutants, indicating VPS11/Pep5p functions at multiple steps in vacuolar trafficking, including at the Golgi-to-prevacuolar compartment step where Vps8p acts.\",\n      \"method\": \"Genetic epistasis (double-mutant analysis), vacuolar hydrolase activity assays, vacuolar morphology assessment\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with functional readouts, single lab, two orthogonal methods\",\n      \"pmids\": [\"9475722\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"C. albicans VPS11 is required for vacuolar biogenesis, secreted lipase and aspartyl protease activities, and yeast-to-hypha morphogenesis; vps11Δ mutants lack a vacuolar compartment and show delayed germ tube emergence and inability to form mature hyphae, indicating VPS11-mediated trafficking is necessary for hyphal growth.\",\n      \"method\": \"Gene deletion, vacuolar morphology assay, enzyme activity assays, morphogenesis induction assay\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean gene deletion with multiple defined phenotypic readouts across orthogonal assays in a fungal model\",\n      \"pmids\": [\"12796286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Loss of Vps11 in zebrafish (platinum mutant, single-nucleotide insertion in vps11) does not block melanophore development, migration, or dispersion, but is essential for melanosome maturation and healthy maintenance of the RPE and photoreceptors, demonstrating a specific role for Vps11 in late organelle biogenesis rather than cell fate.\",\n      \"method\": \"Bulked segregant analysis, candidate gene sequencing, phenocopy and rescue experiments, RT-PCR, in situ hybridization, histology, immunohistochemistry, transmission electron microscopy\",\n      \"journal\": \"Investigative ophthalmology & visual science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — identified causative mutation, phenocopy and rescue experiments, multiple orthogonal morphological methods\",\n      \"pmids\": [\"21330665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In zebrafish vps11(w66) mutants, loss of Vps11 leads to caspase-independent chromatophore death associated with increased cathepsin activity; inhibition of cathepsins/calpain (ALLM) or vacuolar H+-ATPase (Bafilomycin A1) restores normal melanophore morphology and number, and LC3B-II accumulation indicates impaired autophagic flux. This establishes Vps11 as promoting melanophore survival by inhibiting cathepsin release/activity.\",\n      \"method\": \"Zebrafish mutant analysis, TUNEL assay, caspase inhibitor treatment, Western blot for PARP-1 cleavage and LC3B-II, pharmacological inhibition (ALLM, Bafilomycin A1)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (genetic, pharmacological, biochemical), single lab\",\n      \"pmids\": [\"23724125\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"T. gondii Vps11 orthologue (TgVps11) is a dynamic protein that associates with Golgi endosomal-related compartments, the vacuole, and immature apical secretory organelles; conditional knockdown of TgVps11 disrupts biogenesis or proper subcellular localization of dense granules, rhoptries, and micronemes, impairing parasite motility, invasion, egress, and intracellular growth.\",\n      \"method\": \"Conditional knockdown, immunofluorescence/subcellular localization, invasion and motility assays, phenotypic analysis of secretory organelle biogenesis\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knockdown with multiple orthogonal functional readouts confirming essential role in organelle biogenesis\",\n      \"pmids\": [\"25640905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The VPS11 p.Cys846Gly mutation (homologous yeast mutation tested in Mup1-GFP transport assay) causes moderate impairment of fusion of the late endosome to the vacuole, establishing that the C846G variant specifically disrupts the endosomal-vacuolar fusion step.\",\n      \"method\": \"Yeast Mup1-GFP transport assay (functional homologue assay), exome analysis, homozygosity mapping\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional transport assay in yeast model, single lab\",\n      \"pmids\": [\"26307567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The VPS11 C846G (c.2536T>G) missense mutation in humans causes aberrant ubiquitination and accelerated turnover of VPS11 protein, compromised VPS11-VPS18 complex assembly, and impaired autophagic activity; zebrafish with truncated RING-H2 domain show significant reduction in CNS myelination and extensive neuronal death in hindbrain and midbrain.\",\n      \"method\": \"Whole exome sequencing, ubiquitination assays, VPS11-VPS18 co-immunoprecipitation, autophagy flux assays in human cells, zebrafish genetic model with histology\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP for complex assembly, ubiquitination assay, autophagy assay, in vivo zebrafish model), single paper with rigorous controls\",\n      \"pmids\": [\"27120463\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Vps11 and Vps18, as common subunits of HOPS/CORVET complexes, function as E3 ubiquitin ligases; overexpression of Vps11/Vps18 perturbs ubiquitination in signal transduction pathways including Wnt, estrogen receptor α (ERα), and NFκB; specifically, Vps11/18-mediated ubiquitination of the scaffold protein PELP1 impairs activation of ERα by c-Src.\",\n      \"method\": \"Overexpression, ubiquitination assays, signaling pathway readouts (Wnt, ERα, NFκB), co-immunoprecipitation for PELP1 ubiquitination\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — E3 ligase activity demonstrated by ubiquitination assays with specific substrate (PELP1) identified, single lab but multiple pathways tested\",\n      \"pmids\": [\"31015428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"VPS11 is strongly expressed in mouse oligodendrocytes and specifically localizes with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin; Vps11 co-localizes with PDGFRα in round vesicles of OPCs/oligodendrocytes in vitro and in vivo, suggesting a role in retrograde endolysosomal transport from the myelin inner tongue to the oligodendrocyte perikaryon.\",\n      \"method\": \"Immunocytochemistry, immunofluorescent co-staining with MAG, MBP, neurofilament, and PDGFRα markers, in vitro and in vivo co-localization\",\n      \"journal\": \"ASN neuro\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiments with multiple co-markers, single lab, no functional perturbation experiment\",\n      \"pmids\": [\"33874780\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A novel homozygous VPS11 variant causes adult-onset generalized dystonia; functional studies on patient-derived fibroblasts show marked lysosomal and autophagic abnormalities that are rescued by overexpression of wild-type VPS11, establishing the autophagic-lysosomal pathway as the mechanistic basis of VPS11-related disease.\",\n      \"method\": \"Patient fibroblast functional studies (lysosomal/autophagic assays), wild-type VPS11 rescue experiment\",\n      \"journal\": \"Annals of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional rescue experiment with defined autophagy/lysosomal readouts, single lab\",\n      \"pmids\": [\"33452836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Knockdown of Vps11 in human cells increases retrograde Golgi transport of Shiga toxin (Stx) and ricin, and also increases Stx toxicity and ricin toxicity; Vps11 knockdown also restores reduced Gb3 (globotriaosylceramide) glycolipid levels caused by moesin depletion, establishing that Vps11 regulates retrograde toxin transport and glycolipid degradation.\",\n      \"method\": \"siRNA knockdown, Shiga toxin and ricin retrograde transport assays, toxicity assays, Gb3 level measurement\",\n      \"journal\": \"Communicative & integrative biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (knockdown + trafficking readout), brief communication\",\n      \"pmids\": [\"24778763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ALKBH5, an m6A RNA demethylase, alleviates hepatic lipid deposition by removing m6A modification on VPS11 mRNA to promote its translation; overexpression of VPS11 reverses FFA-induced lipid accumulation in ALKBH5-silenced hepatocytes by restoring autophagosome-lysosome fusion (autophagic flux).\",\n      \"method\": \"Overexpression and knockdown of ALKBH5, methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), RNA-seq, VPS11 overexpression rescue, autophagy flux assays (LC3B, p62/SQSTM1), lipid accumulation assays\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — m6A modification mapped on VPS11 mRNA by MeRIP, functional rescue by VPS11 overexpression, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"39434426\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-542-3p targets the 3' UTR of human VPS11 mRNA (seed sequence absent in mice/rats), reducing VPS11 expression in macrophages infected with M. tuberculosis; VPS11 overexpression antagonizes the miR-542-3p-mediated promotion of M. tuberculosis survival by restoring autophagic flux, establishing VPS11 as a key autophagy regulator in anti-mycobacterial defense.\",\n      \"method\": \"Luciferase reporter assay, RNA pulldown, RNA immunoprecipitation, VPS11 overexpression in macrophages, M. tuberculosis survival assay, autophagy flux assays\",\n      \"journal\": \"Microbial pathogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct miRNA target validation by luciferase reporter and RNA pulldown, functional rescue experiment, single lab\",\n      \"pmids\": [\"35662671\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS11 is a core structural subunit of the HOPS and CORVET endolysosomal tethering complexes that functions as an E3 ubiquitin ligase and is essential for vacuolar/lysosomal biogenesis, late endosome-to-lysosome fusion, autophagic flux, and melanosome maturation; disease-causing mutations (notably p.Cys846Gly in the RING-H2 domain) disrupt VPS11-VPS18 complex assembly, cause aberrant ubiquitination and accelerated VPS11 turnover, impair autophagosome-lysosome fusion, and in vivo lead to hypomyelination, neurodegeneration, and lysosomal storage, while VPS11 expression is post-transcriptionally regulated by m6A demethylation of its mRNA by ALKBH5.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"VPS11 is a core subunit of the endolysosomal/vacuolar tethering machinery that drives delivery of proteins to the vacuole/lysosome and the maturation of late organelles across eukaryotes [#0, #2]. First defined in yeast as a peripheral vacuolar membrane protein essential for vacuolar biogenesis and the proteolytic maturation of vacuolar hydrolases [#0], it acts at multiple trafficking steps including the Golgi-to-prevacuolar route and, critically, the fusion of late endosomes with the vacuole/lysosome [#1, #6]. As a shared subunit of the HOPS/CORVET complexes it carries E3 ubiquitin ligase activity, ubiquitinating substrates such as the scaffold PELP1 to modulate ER\\u03b1, Wnt, and NF\\u03baB signaling [#8]. Across organisms VPS11 is required for late organelle biogenesis rather than cell fate: melanosome maturation and RPE/photoreceptor maintenance in zebrafish [#3], and biogenesis of secretory organelles (dense granules, rhoptries, micronemes) in Toxoplasma [#5]. A central downstream function is the support of autophagic flux through autophagosome-lysosome fusion [#7, #10]. The human VPS11 C846G mutation in the RING-H2 domain causes aberrant ubiquitination and accelerated turnover of VPS11, compromised VPS11-VPS18 complex assembly, and impaired autophagy, producing CNS hypomyelination and neuronal death; other homozygous variants cause adult-onset generalized dystonia, with patient-fibroblast lysosomal and autophagic defects rescued by wild-type VPS11 [#7, #10]. VPS11 expression is post-transcriptionally tuned: ALKBH5-mediated m6A demethylation of VPS11 mRNA promotes its translation [#12], and miR-542-3p targets its 3' UTR to suppress autophagy-dependent anti-mycobacterial defense [#13].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Established that VPS11 is required for biogenesis of the vacuole and delivery/maturation of vacuolar hydrolases, defining its foundational role in endolysosomal trafficking.\",\n      \"evidence\": \"Gene deletion, cell fractionation, and immunoblot of vacuolar hydrolase precursors in S. cerevisiae\",\n      \"pmids\": [\"2204580\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the molecular complex or tethering mechanism\", \"No mammalian ortholog characterized\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Showed VPS11 acts at multiple trafficking steps, including the Golgi-to-prevacuolar step where Vps8p operates, refining where in the pathway it functions.\",\n      \"evidence\": \"Genetic epistasis (vps8/pep5 double mutants) with vacuolar hydrolase and morphology readouts in yeast\",\n      \"pmids\": [\"9475722\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genetic suppression does not establish direct physical interaction\", \"Step-specific molecular role unresolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Extended VPS11 function to fungal organelle biogenesis and linked vacuolar trafficking to hyphal morphogenesis and secreted enzyme activity.\",\n      \"evidence\": \"Gene deletion with vacuolar morphology, enzyme activity, and morphogenesis assays in C. albicans\",\n      \"pmids\": [\"12796286\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Link between trafficking defect and morphogenesis mechanistically indirect\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated VPS11 is dispensable for cell fate but essential for late organelle maturation, distinguishing a biogenesis role from a developmental one.\",\n      \"evidence\": \"Zebrafish platinum mutant with phenocopy/rescue, histology, and electron microscopy of melanosomes, RPE, and photoreceptors\",\n      \"pmids\": [\"21330665\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of melanosome maturation defect not defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Connected VPS11 loss to impaired autophagic flux and cathepsin-driven cell death, implicating the lysosomal degradation pathway in VPS11 phenotypes.\",\n      \"evidence\": \"Zebrafish mutant with TUNEL, LC3B-II Western blot, and pharmacological inhibition of cathepsins/calpain and V-ATPase\",\n      \"pmids\": [\"23724125\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal chain from autophagy block to cathepsin release inferred pharmacologically\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Pinpointed the disease C846G variant to the late endosome-to-vacuole fusion step using a functional homolog assay, mechanistically localizing the defect.\",\n      \"evidence\": \"Yeast Mup1-GFP transport assay of the homologous mutation, plus exome and homozygosity mapping\",\n      \"pmids\": [\"26307567\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Assay in yeast surrogate, not human cells\", \"Impairment characterized as moderate\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showed VPS11 supports secretory organelle biogenesis and parasite infectivity, broadening its organelle-maturation role to apicomplexan secretory pathways.\",\n      \"evidence\": \"Conditional knockdown with immunofluorescence localization and invasion/motility/egress assays in T. gondii\",\n      \"pmids\": [\"25640905\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct tethering partners in the parasite not identified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined the molecular consequences of the human C846G RING-H2 mutation, linking disrupted VPS11-VPS18 assembly and aberrant ubiquitination to impaired autophagy and CNS hypomyelination.\",\n      \"evidence\": \"Whole exome sequencing, ubiquitination and Co-IP assays, autophagy flux assays in human cells, and zebrafish RING-H2 truncation model\",\n      \"pmids\": [\"27120463\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of complex destabilization not resolved\", \"E3 ligase activity not directly addressed here\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified VPS11/VPS18 as functional E3 ubiquitin ligases acting on signaling substrates, expanding VPS11 beyond membrane tethering into signal-pathway regulation.\",\n      \"evidence\": \"Overexpression and ubiquitination assays across Wnt/ER\\u03b1/NF\\u03baB pathways with Co-IP of PELP1 ubiquitination\",\n      \"pmids\": [\"31015428\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Demonstrated by overexpression; physiological context unclear\", \"Direct catalytic mechanism not reconstituted\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Localized VPS11 to oligodendrocyte myelin and endolysosomal vesicles, providing a cellular basis for VPS11-related hypomyelination.\",\n      \"evidence\": \"Immunocytochemistry and co-staining with MAG, MBP, PDGFR\\u03b1 in mouse oligodendrocytes in vitro and in vivo\",\n      \"pmids\": [\"33874780\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional perturbation experiment\", \"Retrograde transport role inferred from co-localization\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linked a distinct VPS11 variant to adult-onset dystonia and established the autophagic-lysosomal pathway as the disease mechanism via rescue.\",\n      \"evidence\": \"Patient fibroblast lysosomal/autophagic assays rescued by wild-type VPS11 overexpression\",\n      \"pmids\": [\"33452836\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single family/lab\", \"Genotype-phenotype relationship to other VPS11 variants not resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed VPS11 is a post-transcriptionally regulated autophagy effector in anti-mycobacterial immunity, with miR-542-3p suppressing it to favor pathogen survival.\",\n      \"evidence\": \"Luciferase reporter, RNA pulldown/IP, VPS11 overexpression rescue, and M. tuberculosis survival/autophagy assays in macrophages\",\n      \"pmids\": [\"35662671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"miR target site human-specific\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified m6A demethylation by ALKBH5 as a translational control mechanism for VPS11, linking VPS11-dependent autophagic flux to hepatic lipid homeostasis.\",\n      \"evidence\": \"ALKBH5 manipulation, MeRIP-qPCR on VPS11 mRNA, VPS11 overexpression rescue, and autophagy/lipid assays in hepatocytes\",\n      \"pmids\": [\"39434426\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reader protein decoding the m6A mark not identified\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How VPS11's tethering, E3 ligase, and complex-assembly functions are mechanistically integrated, and the structural basis by which disease mutations destabilize the HOPS/CORVET core, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of VPS11 within HOPS/CORVET\", \"Catalytic E3 mechanism not reconstituted in vitro\", \"Relationship between ubiquitin ligase activity and membrane tethering unclear\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005773\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [6, 9]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [5, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7, 10, 13]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 6, 11]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [3, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [\"HOPS\", \"CORVET\"],\n    \"partners\": [\"VPS18\", \"VPS8\", \"PELP1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":7,"faith_pct":85.71428571428571}}