{"gene":"VPS51","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":2002,"finding":"Yeast Vps51 (Ykr020w) is a subunit of the Vps fifty-three (VFT/GARP) tethering complex, composed of Vps52, Vps53, and Vps54. Vps51 is required for retrograde traffic from the early endosome back to the late Golgi and for Cvt vesicle formation. Loss of Vps51 blocks correct targeting of the prApe1-Cvt19-Cvt9 complex to the preautophagosomal structure and reduces autophagosome size.","method":"Genetic deletion, co-immunoprecipitation, fluorescence microscopy, maturation assays for prApe1 and Ape1","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP, multiple genetic and cell biological readouts in founding study; replicated by subsequent work","pmids":["12446664"],"is_preprint":false},{"year":2006,"finding":"The N-terminal domain of yeast Tlg1 (a TGN SNARE) binds directly to a short N-terminal peptide (residues 18–30) of Vps51, forming a helix that docks into a conserved groove of Tlg1's three-helix bundle. Despite this physical interaction, deletion of the Tlg1-binding sequences from Vps51 does not block endosome-to-Golgi transport in vivo, indicating this interaction is not essential for vesicle docking or fusion.","method":"X-ray crystallography of Tlg1 N-terminal domain bound to Vps51 peptide; in vivo trafficking assays with truncation mutants","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 1 — crystal structure with functional mutagenesis in vivo","pmids":["16420526"],"is_preprint":false},{"year":2010,"finding":"Human Ang2 (the VPS51 ortholog, also called Fat-free) is the missing fourth subunit of the human GARP complex, interacting with human Vps52, Vps53, and Vps54 in an obligatory 1:1:1:1 stoichiometry. Human Ang2/VPS51 exhibits significant homology to yeast Vps51p in an N-terminal coiled-coil region that mediates assembly with other GARP subunits. The complex strongly interacts with the regulatory Habc domain of the TGN SNARE Syntaxin 6. Depletion of Ang2/VPS51 impairs protein retrieval to the TGN, lysosomal enzyme sorting, endosomal cholesterol trafficking, and autophagy.","method":"Yeast two-hybrid screen, co-immunoprecipitation, biochemical fractionation, siRNA knockdown with functional trafficking assays (CI-MPR distribution, filipin staining for cholesterol, LC3 flux)","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including reconstitution of 4-subunit complex stoichiometry, reciprocal co-IP, and multiple functional readouts","pmids":["20685960"],"is_preprint":false},{"year":2011,"finding":"The C. elegans GARP complex contains a conserved Vps51 subunit. GARP mutants are viable but display lysosomal morphology defects. C. elegans GARP subunits bind specific sets of Golgi SNAREs in yeast two-hybrid assays, consistent with a role in tethering and SNARE complex assembly at the Golgi. Loss of both GARP and COG tethering complexes produces a synthetic lethal phenotype, indicating overlapping functions in retrograde endosome-to-Golgi retrieval.","method":"Genetic deletion/RNAi, yeast two-hybrid, lysosome morphology assays, synthetic lethality screen","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with synthetic lethality, Y2H binding, and morphological phenotype; independent confirmation in metazoan model","pmids":["21613545"],"is_preprint":false},{"year":2015,"finding":"EARP (endosome-associated recycling protein) is a heterotetrameric tethering complex that shares three subunits with GARP — Ang2/VPS51, Vps52, and Vps53 — but contains syndetin instead of Vps54. The differential fourth subunit determines distinct localization: EARP localizes to recycling endosomes while GARP localizes to the TGN. EARP interacts with syntaxin 6 and promotes fusion of endocytic carriers with recycling endosomes; depletion of syndetin or syntaxin 6 delays transferrin recycling to the cell surface.","method":"Affinity purification–mass spectrometry, co-immunoprecipitation, confocal immunofluorescence, transferrin recycling assays with siRNA knockdown","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 — AP-MS complex identification with reciprocal co-IP, localization by imaging, and functional recycling assay; published in high-impact journal","pmids":["25799061"],"is_preprint":false},{"year":2019,"finding":"Compound heterozygous mutations in VPS51 cause a severe neurodevelopmental disorder in humans, characterized by global developmental delay, microcephaly, epilepsy, pontocerebellar abnormalities, and liver dysfunction. One allele produces a frameshift generating a longer but unstable protein degraded by the proteasome; the other produces a stable protein with a single amino acid substitution that assembles less efficiently with other GARP/EARP subunits. Patient fibroblasts have reduced levels of fully assembled GARP and EARP complexes, show altered distribution of the cation-independent mannose 6-phosphate receptor (CI-MPR), and exhibit lysosomal swelling in a fraction of cells.","method":"Exome sequencing, protein stability assays (proteasome inhibitor rescue), co-immunoprecipitation to measure complex assembly, CI-MPR immunofluorescence, lysosome morphology by microscopy","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods in patient-derived cells linking VPS51 mutations to reduced GARP/EARP assembly and lysosomal trafficking defects","pmids":["30624672"],"is_preprint":false},{"year":2019,"finding":"A homozygous intragenic deletion in VPS51 was identified in two siblings with postnatal microcephaly, severe intellectual disability, cerebellar atrophy, and hypoplastic corpus callosum, independently confirming VPS51 as a genetic locus for neurodevelopmental brain malformations and establishing that VPS51-dependent GARP/EARP function is required for normal brain development.","method":"Whole exome sequencing, homozygosity mapping","journal":"European journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 3 — genetic identification only, no biochemical functional follow-up in this report; corroborates PMID 30624672","pmids":["31207318"],"is_preprint":false}],"current_model":"VPS51 is a shared subunit of two heterotetrameric membrane tethering complexes — GARP (with VPS52, VPS53, VPS54) at the trans-Golgi network and EARP (with VPS52, VPS53, syndetin) at recycling endosomes — where it engages TGN SNAREs (Syntaxin 6; yeast Tlg1) via a conserved N-terminal coiled-coil to promote fusion of endosome-derived transport carriers, thereby mediating retrograde endosome-to-TGN retrieval, lysosomal enzyme sorting, endosomal cholesterol trafficking, autophagy, and endocytic receptor recycling; loss-of-function mutations in humans cause a severe neurodevelopmental disorder with microcephaly, pontocerebellar abnormalities, and lysosomal dysfunction."},"narrative":{"teleology":[{"year":2002,"claim":"Identification of Vps51 as the fourth subunit of the yeast VFT/GARP tethering complex established that retrograde endosome-to-Golgi transport and autophagosome biogenesis require a dedicated tethering factor beyond Vps52–54.","evidence":"Genetic deletion, reciprocal co-IP, fluorescence microscopy, and prApe1 maturation assays in S. cerevisiae","pmids":["12446664"],"confidence":"High","gaps":["No structural information on Vps51 or its contacts within the GARP complex","Mechanism by which Vps51 contributes to autophagosome size regulation unknown"]},{"year":2006,"claim":"A crystal structure of the Tlg1 N-terminal domain bound to a Vps51 peptide revealed the molecular basis for SNARE engagement but showed this interaction is dispensable for retrograde transport, raising the question of what other tethering contacts are essential.","evidence":"X-ray crystallography of Tlg1–Vps51 peptide complex; in vivo trafficking assays with Vps51 truncation mutants in yeast","pmids":["16420526"],"confidence":"High","gaps":["Essential Vps51 domains for vesicle docking and fusion remain unidentified","No structure of full-length Vps51 or intact GARP complex"]},{"year":2010,"claim":"Demonstration that human Ang2/VPS51 is the missing fourth subunit of mammalian GARP extended the complex to metazoans and connected it to Syntaxin 6 engagement, lysosomal enzyme sorting, cholesterol trafficking, and autophagy.","evidence":"Yeast two-hybrid, co-IP, biochemical fractionation, siRNA knockdown with CI-MPR, filipin, and LC3 flux assays in human cells","pmids":["20685960"],"confidence":"High","gaps":["Relative contributions of GARP versus other tethers to each trafficking pathway not delineated","Whether VPS51 has functions independent of the GARP complex was untested"]},{"year":2011,"claim":"Genetic analysis in C. elegans showed GARP (including Vps51) is conserved in metazoans and functionally overlaps with the COG complex, establishing redundancy among Golgi-resident tethers.","evidence":"Genetic deletion/RNAi, yeast two-hybrid SNARE binding, lysosome morphology, and synthetic lethality with COG mutants in C. elegans","pmids":["21613545"],"confidence":"High","gaps":["Molecular basis of GARP–COG functional overlap not resolved","Tissue-specific requirements for Vps51 in multicellular organisms unexplored"]},{"year":2015,"claim":"Discovery of the EARP complex revealed that VPS51 is shared between two functionally distinct tethering complexes — GARP at the TGN and EARP at recycling endosomes — with the differential fourth subunit (VPS54 vs. syndetin) dictating localization and cargo specificity.","evidence":"AP-MS, reciprocal co-IP, confocal immunofluorescence, and transferrin recycling assays with siRNA knockdown in human cells","pmids":["25799061"],"confidence":"High","gaps":["Mechanism by which VPS51 switches between GARP and EARP assembly is unknown","Structural basis for EARP-specific localization to recycling endosomes not determined"]},{"year":2019,"claim":"Identification of biallelic VPS51 mutations in patients with severe neurodevelopmental disease, supported by impaired GARP/EARP assembly and retrograde trafficking defects in patient cells, established VPS51 as a disease gene and demonstrated that both complexes are required for normal brain development.","evidence":"Exome sequencing, proteasome inhibitor rescue of mutant protein, co-IP for complex assembly, CI-MPR and lysosome morphology in patient fibroblasts; independent family with homozygous deletion confirmed by homozygosity mapping","pmids":["30624672","31207318"],"confidence":"High","gaps":["Cell-type-specific contributions (neuronal vs. glial) of VPS51 loss to brain malformation not resolved","Whether residual EARP function partially compensates for GARP loss (or vice versa) in patient cells is unknown","No animal model recapitulating the full human phenotype has been reported"]},{"year":null,"claim":"Key open questions include the structural basis of the intact GARP and EARP complexes, the mechanism governing VPS51 partitioning between GARP and EARP, and the neuron-specific pathways through which VPS51 deficiency leads to pontocerebellar hypoplasia.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of full-length VPS51 or assembled GARP/EARP complexes","Regulatory mechanisms controlling VPS51 allocation between GARP and EARP are unknown","Neuron-type-specific vulnerability to VPS51 loss not characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,4]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,4]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2,4]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,4,5]}],"complexes":["GARP (VPS51–VPS52–VPS53–VPS54)","EARP (VPS51–VPS52–VPS53–syndetin)"],"partners":["VPS52","VPS53","VPS54","SYNDETIN","STX6","TLG1"],"other_free_text":[]},"mechanistic_narrative":"VPS51 is a shared subunit of two heterotetrameric membrane-tethering complexes — GARP (with VPS52, VPS53, VPS54) at the trans-Golgi network and EARP (with VPS52, VPS53, syndetin) at recycling endosomes — that promote SNARE-dependent fusion of endosome-derived transport carriers [PMID:12446664, PMID:25799061]. VPS51 assembles into these complexes via a conserved N-terminal coiled-coil that also engages TGN SNAREs (Syntaxin 6 in mammals; Tlg1 in yeast), thereby coordinating tethering with fusion-competent SNARE complex formation [PMID:16420526, PMID:20685960]. Through GARP, VPS51 supports retrograde endosome-to-Golgi retrieval of cargo such as the cation-independent mannose 6-phosphate receptor, endosomal cholesterol trafficking, lysosomal enzyme sorting, and autophagy; through EARP, it facilitates recycling of endocytic receptors to the plasma membrane [PMID:20685960, PMID:25799061]. Biallelic loss-of-function mutations in VPS51 cause a severe neurodevelopmental disorder with microcephaly, pontocerebellar abnormalities, epilepsy, and lysosomal dysfunction, linked to impaired GARP/EARP complex assembly and defective retrograde trafficking [PMID:30624672, PMID:31207318]."},"prefetch_data":{"uniprot":{"accession":"Q9UID3","full_name":"Vacuolar protein sorting-associated protein 51 homolog","aliases":["Another new gene 2 protein","Protein fat-free homolog"],"length_aa":782,"mass_kda":86.0,"function":"Acts as a component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome-derived carriers to the TGN (PubMed:20685960). Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061)","subcellular_location":"Golgi apparatus, trans-Golgi network; Recycling endosome","url":"https://www.uniprot.org/uniprotkb/Q9UID3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/VPS51","classification":"Common Essential","n_dependent_lines":863,"n_total_lines":1208,"dependency_fraction":0.7144039735099338},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/VPS51","total_profiled":1310},"omim":[{"mim_id":"619397","title":"ZINC FINGER PROTEIN-LIKE 1; ZFPL1","url":"https://www.omim.org/entry/619397"},{"mim_id":"618606","title":"PONTOCEREBELLAR HYPOPLASIA, TYPE 13; PCH13","url":"https://www.omim.org/entry/618606"},{"mim_id":"616465","title":"VPS50, EARP/GARPII COMPLEX SUBUNIT; VPS50","url":"https://www.omim.org/entry/616465"},{"mim_id":"615850","title":"VPS53 SUBUNIT OF GARP COMPLEX; VPS53","url":"https://www.omim.org/entry/615850"},{"mim_id":"615738","title":"VPS51 SUBUNIT OF GARP COMPLEX; VPS51","url":"https://www.omim.org/entry/615738"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/VPS51"},"hgnc":{"alias_symbol":["ANG2","ANG3","FFR"],"prev_symbol":["C11orf3","C11orf2"]},"alphafold":{"accession":"Q9UID3","domains":[{"cath_id":"1.20.58","chopping":"265-390","consensus_level":"high","plddt":86.1274,"start":265,"end":390},{"cath_id":"1.20.1310","chopping":"410-431_442-513_520-560","consensus_level":"high","plddt":90.6987,"start":410,"end":560},{"cath_id":"1.20.58","chopping":"584-633_688-782","consensus_level":"high","plddt":89.9659,"start":584,"end":782}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UID3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UID3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UID3-F1-predicted_aligned_error_v6.png","plddt_mean":80.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VPS51","jax_strain_url":"https://www.jax.org/strain/search?query=VPS51"},"sequence":{"accession":"Q9UID3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UID3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UID3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UID3"}},"corpus_meta":[{"pmid":"21481792","id":"PMC_21481792","title":"Targeting 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signaling","url":"https://pubmed.ncbi.nlm.nih.gov/25921289","citation_count":61,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":54797,"output_tokens":1803,"usd":0.095718},"stage2":{"model":"claude-opus-4-6","input_tokens":5041,"output_tokens":1919,"usd":0.10977},"total_usd":0.452306,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":66355,"output_tokens":2795,"usd":0.120495},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5753,"output_tokens":2218,"usd":0.126323}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"VPS51 (Ykr020w) is a subunit of the yeast GARP (Vps fifty-three) tethering complex, composed of Vps52, Vps53, and Vps54, which is required for retrograde traffic from the early endosome back to the late Golgi. VPS51 is also essential for Cvt vesicle formation and acts together with the SNAREs Tlg1 and Tlg2 to correctly target the prApe1-Cvt19-Cvt9 complex to the preautophagosomal structure.\",\n      \"method\": \"Genetic deletion, yeast two-hybrid, co-immunoprecipitation, fluorescence microscopy, biochemical fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (genetics, Co-IP, imaging) in a single study establishing complex membership and function\",\n      \"pmids\": [\"12446664\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The N-terminal domain of yeast Vps51 binds specifically to the SNARE Tlg1 via residues 18–30 of Vps51, which form a short helix lying in a conserved groove of the Tlg1 three-helix bundle (Habc domain). Despite this interaction, removal of the Tlg1-binding sequences from Vps51 does not block endosome-to-Golgi traffic in vivo, indicating this specific interaction is not essential for vesicle docking or fusion.\",\n      \"method\": \"Crystal structure of Tlg1 N-terminal domain bound to Vps51 peptide; in vivo deletion analysis\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure combined with mutagenesis and in vivo functional validation\",\n      \"pmids\": [\"16420526\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Human VPS51 (Ang2/Fat-free) is the missing fourth subunit of the mammalian GARP complex. It interacts with human VPS52, VPS53, and VPS54 via an N-terminal coiled-coil region homologous to yeast Vps51p, forming an obligatory 1:1:1:1 heterotetramer. The GARP complex strongly interacts with the regulatory Habc domain of the TGN SNARE Syntaxin 6. Depletion of VPS51 or other GARP subunits impairs protein retrieval to the TGN, lysosomal enzyme sorting, endosomal cholesterol trafficking, and autophagy.\",\n      \"method\": \"Yeast two-hybrid screen, Co-immunoprecipitation, siRNA depletion, biochemical fractionation, fluorescence microscopy\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — yeast two-hybrid discovery confirmed by reciprocal Co-IP, complex reconstitution, and multiple functional assays in human cells\",\n      \"pmids\": [\"20685960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The C. elegans GARP complex contains a conserved VPS51 subunit (ortholog identified). GARP mutants are viable but show lysosomal morphology defects. GARP subunits bind specific sets of Golgi SNAREs in yeast two-hybrid assays, supporting a tethering and SNARE complex assembly role at the Golgi. Loss of both GARP and COG complexes causes a synthetic lethal phenotype, suggesting overlapping functions in retrograde endosome-to-Golgi retrieval.\",\n      \"method\": \"Genetic deletion, yeast two-hybrid, electron microscopy of lysosomal morphology, synthetic lethality screen\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods; genetic epistasis (synthetic lethality) firmly places GARP/VPS51 in the retrograde trafficking pathway\",\n      \"pmids\": [\"21613545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Compound heterozygous loss-of-function mutations in human VPS51 cause a severe neurodevelopmental disorder. One allele produces a frameshifted, proteasome-degraded protein; the other produces a stable protein with a single amino acid substitution that assembles less efficiently into GARP/EARP complexes. Patient fibroblasts have reduced levels of fully assembled GARP and EARP complexes, altered cation-independent mannose 6-phosphate receptor (CI-M6PR) distribution, and lysosomal swelling, demonstrating that VPS51 is required for proper endosome-to-TGN retrograde transport and lysosomal enzyme sorting in human cells.\",\n      \"method\": \"Exome sequencing, co-immunoprecipitation to assess complex assembly, immunofluorescence microscopy of CI-M6PR distribution and lysosomal morphology, proteasome inhibition assay\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean human loss-of-function with multiple orthogonal mechanistic readouts (complex assembly, receptor trafficking, organelle morphology)\",\n      \"pmids\": [\"30624672\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Biallelic intragenic deletion in VPS51 in two siblings causes postnatal microcephaly with brain malformations, confirming that VPS51 dysfunction disrupts normal brain development, consistent with its role in GARP/EARP-mediated membrane trafficking.\",\n      \"method\": \"Whole exome sequencing, identification of homozygous deletion\",\n      \"journal\": \"European journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic finding in humans confirming pathogenicity; no additional biochemical mechanistic data beyond prior report\",\n      \"pmids\": [\"31207318\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS51 is the fourth, phylogenetically conserved subunit of the heterotetrameric GARP (and EARP) tethering complex; it assembles with VPS52, VPS53, and VPS54 via an N-terminal coiled-coil domain, directly binds the Habc domain of the TGN SNARE Syntaxin 6 (and yeast Tlg1), and is required for tethering and fusion of endosome-derived transport carriers at the trans-Golgi network, thereby enabling retrograde retrieval of lysosomal sorting receptors, proper lysosomal enzyme sorting, and normal lysosomal morphology; loss of VPS51 in humans causes lysosomal dysfunction and a severe neurodevelopmental disorder.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper before extracting discoveries.\n\n**Classification:**\n\n**KEEP (about canonical VPS51 protein):**\n- PMID 12446664: Yeast Vps51 — foundational paper identifying Vps51 as GARP subunit (ortholog)\n- PMID 20685960: Ang2/Fat-free as conserved VPS51 ortholog in human GARP complex\n- PMID 16420526: Structure of Tlg1-Vps51 interaction (yeast ortholog)\n- PMID 30624672: Human VPS51 mutations cause neurodevelopmental disorder\n- PMID 31207318: VPS51 biallelic variants cause microcephaly (confirmatory)\n- PMID 21613545: C. elegans GARP complex with Vps51 subunit (ortholog)\n- PMID 25799061: EARP complex shares Ang2/VPS51 with GARP\n- PMID 24757006: Arabidopsis VPS51 homolog — EXCLUDE (plant, fundamentally different context/symbol collision)\n- PMID 26186194: BioPlex — interactome (mentions VPS51 interactions)\n- PMID 28514442: BioPlex 2.0\n- PMID 33961781: BioPlex 3.0\n- PMID 26496610: Human interactome (Hein et al.)\n- PMID 22939629: Census of human complexes\n- PMID 34079125: BioID map\n\nMost of the remaining papers are about Angiopoietin-2 (ANGPT2/Ang-2), a completely different gene. The \"Ang2\" in papers [11] and [25] refers to the VPS51 ortholog (also called Ang2/Fat-free), not ANGPT2. Papers about ANGPT2 are alias collisions — EXCLUDE.\n\nPMID 24757006 (Arabidopsis UNH/VPS51 homolog) — this describes plant development with fundamentally incompatible cellular context → EXCLUDE as symbol collision in plants.\n\nThe large-scale interactome papers (BioPlex etc.) identify VPS51 interactions but provide no mechanistic detail beyond co-complex membership — I'll include them only if they add specific binding partner information.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"Yeast Vps51 (Ykr020w) is a subunit of the Vps fifty-three (VFT/GARP) tethering complex, composed of Vps52, Vps53, and Vps54. Vps51 is required for retrograde traffic from the early endosome back to the late Golgi and for Cvt vesicle formation. Loss of Vps51 blocks correct targeting of the prApe1-Cvt19-Cvt9 complex to the preautophagosomal structure and reduces autophagosome size.\",\n      \"method\": \"Genetic deletion, co-immunoprecipitation, fluorescence microscopy, maturation assays for prApe1 and Ape1\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, multiple genetic and cell biological readouts in founding study; replicated by subsequent work\",\n      \"pmids\": [\"12446664\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The N-terminal domain of yeast Tlg1 (a TGN SNARE) binds directly to a short N-terminal peptide (residues 18–30) of Vps51, forming a helix that docks into a conserved groove of Tlg1's three-helix bundle. Despite this physical interaction, deletion of the Tlg1-binding sequences from Vps51 does not block endosome-to-Golgi transport in vivo, indicating this interaction is not essential for vesicle docking or fusion.\",\n      \"method\": \"X-ray crystallography of Tlg1 N-terminal domain bound to Vps51 peptide; in vivo trafficking assays with truncation mutants\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure with functional mutagenesis in vivo\",\n      \"pmids\": [\"16420526\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Human Ang2 (the VPS51 ortholog, also called Fat-free) is the missing fourth subunit of the human GARP complex, interacting with human Vps52, Vps53, and Vps54 in an obligatory 1:1:1:1 stoichiometry. Human Ang2/VPS51 exhibits significant homology to yeast Vps51p in an N-terminal coiled-coil region that mediates assembly with other GARP subunits. The complex strongly interacts with the regulatory Habc domain of the TGN SNARE Syntaxin 6. Depletion of Ang2/VPS51 impairs protein retrieval to the TGN, lysosomal enzyme sorting, endosomal cholesterol trafficking, and autophagy.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, biochemical fractionation, siRNA knockdown with functional trafficking assays (CI-MPR distribution, filipin staining for cholesterol, LC3 flux)\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including reconstitution of 4-subunit complex stoichiometry, reciprocal co-IP, and multiple functional readouts\",\n      \"pmids\": [\"20685960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The C. elegans GARP complex contains a conserved Vps51 subunit. GARP mutants are viable but display lysosomal morphology defects. C. elegans GARP subunits bind specific sets of Golgi SNAREs in yeast two-hybrid assays, consistent with a role in tethering and SNARE complex assembly at the Golgi. Loss of both GARP and COG tethering complexes produces a synthetic lethal phenotype, indicating overlapping functions in retrograde endosome-to-Golgi retrieval.\",\n      \"method\": \"Genetic deletion/RNAi, yeast two-hybrid, lysosome morphology assays, synthetic lethality screen\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with synthetic lethality, Y2H binding, and morphological phenotype; independent confirmation in metazoan model\",\n      \"pmids\": [\"21613545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"EARP (endosome-associated recycling protein) is a heterotetrameric tethering complex that shares three subunits with GARP — Ang2/VPS51, Vps52, and Vps53 — but contains syndetin instead of Vps54. The differential fourth subunit determines distinct localization: EARP localizes to recycling endosomes while GARP localizes to the TGN. EARP interacts with syntaxin 6 and promotes fusion of endocytic carriers with recycling endosomes; depletion of syndetin or syntaxin 6 delays transferrin recycling to the cell surface.\",\n      \"method\": \"Affinity purification–mass spectrometry, co-immunoprecipitation, confocal immunofluorescence, transferrin recycling assays with siRNA knockdown\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — AP-MS complex identification with reciprocal co-IP, localization by imaging, and functional recycling assay; published in high-impact journal\",\n      \"pmids\": [\"25799061\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Compound heterozygous mutations in VPS51 cause a severe neurodevelopmental disorder in humans, characterized by global developmental delay, microcephaly, epilepsy, pontocerebellar abnormalities, and liver dysfunction. One allele produces a frameshift generating a longer but unstable protein degraded by the proteasome; the other produces a stable protein with a single amino acid substitution that assembles less efficiently with other GARP/EARP subunits. Patient fibroblasts have reduced levels of fully assembled GARP and EARP complexes, show altered distribution of the cation-independent mannose 6-phosphate receptor (CI-MPR), and exhibit lysosomal swelling in a fraction of cells.\",\n      \"method\": \"Exome sequencing, protein stability assays (proteasome inhibitor rescue), co-immunoprecipitation to measure complex assembly, CI-MPR immunofluorescence, lysosome morphology by microscopy\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods in patient-derived cells linking VPS51 mutations to reduced GARP/EARP assembly and lysosomal trafficking defects\",\n      \"pmids\": [\"30624672\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"A homozygous intragenic deletion in VPS51 was identified in two siblings with postnatal microcephaly, severe intellectual disability, cerebellar atrophy, and hypoplastic corpus callosum, independently confirming VPS51 as a genetic locus for neurodevelopmental brain malformations and establishing that VPS51-dependent GARP/EARP function is required for normal brain development.\",\n      \"method\": \"Whole exome sequencing, homozygosity mapping\",\n      \"journal\": \"European journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic identification only, no biochemical functional follow-up in this report; corroborates PMID 30624672\",\n      \"pmids\": [\"31207318\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS51 is a shared subunit of two heterotetrameric membrane tethering complexes — GARP (with VPS52, VPS53, VPS54) at the trans-Golgi network and EARP (with VPS52, VPS53, syndetin) at recycling endosomes — where it engages TGN SNAREs (Syntaxin 6; yeast Tlg1) via a conserved N-terminal coiled-coil to promote fusion of endosome-derived transport carriers, thereby mediating retrograde endosome-to-TGN retrieval, lysosomal enzyme sorting, endosomal cholesterol trafficking, autophagy, and endocytic receptor recycling; loss-of-function mutations in humans cause a severe neurodevelopmental disorder with microcephaly, pontocerebellar abnormalities, and lysosomal dysfunction.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"VPS51 is the fourth subunit of the heterotetrameric GARP tethering complex (VPS51–VPS52–VPS53–VPS54), conserved from yeast to humans, that mediates retrograde transport of endosome-derived carriers to the trans-Golgi network (TGN) [PMID:12446664, PMID:20685960]. VPS51 assembles into the complex via an N-terminal coiled-coil domain and directly binds the Habc domain of TGN SNAREs (Tlg1 in yeast, Syntaxin 6 in mammals), coupling vesicle tethering to SNARE-mediated fusion [PMID:16420526, PMID:20685960]. Loss of VPS51 impairs retrieval of the cation-independent mannose 6-phosphate receptor to the TGN, disrupts lysosomal enzyme sorting, causes lysosomal swelling, and compromises autophagy [PMID:20685960, PMID:21613545, PMID:30624672]. Biallelic loss-of-function mutations in human VPS51 cause a severe neurodevelopmental disorder with postnatal microcephaly, linked to diminished GARP and EARP complex assembly [PMID:30624672, PMID:31207318].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Identification of VPS51 as a subunit of the yeast GARP complex established that retrograde endosome-to-Golgi tethering requires a fourth, previously unrecognized component and linked VPS51 to SNARE-dependent trafficking and Cvt pathway vesicle formation.\",\n      \"evidence\": \"Genetic deletion, yeast two-hybrid, Co-IP, and fluorescence microscopy in S. cerevisiae\",\n      \"pmids\": [\"12446664\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of VPS51 interaction with SNARE proteins was unknown\",\n        \"Whether a VPS51 ortholog exists in mammalian GARP was not established\",\n        \"Relative contributions of VPS51 to tethering versus SNARE complex assembly were unclear\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Structural determination of the VPS51–Tlg1 interface revealed that VPS51 residues 18–30 form a helix that docks into a conserved groove of the Tlg1 Habc domain, yet deletion of these residues did not block retrograde traffic, showing this SNARE interaction is dispensable for the core tethering function.\",\n      \"evidence\": \"Crystal structure of Tlg1 Habc–Vps51 peptide complex; in vivo truncation analysis in yeast\",\n      \"pmids\": [\"16420526\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether additional VPS51 surfaces mediate functionally essential SNARE contacts was unresolved\",\n        \"Mammalian relevance of this interaction remained untested\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identification of human VPS51 (Ang2) as the fourth GARP subunit extended the complex to mammals and showed that GARP forms an obligatory 1:1:1:1 heterotetramer that binds Syntaxin 6 and is required for TGN retrieval, lysosomal enzyme sorting, cholesterol trafficking, and autophagy in human cells.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP, siRNA knockdown, and functional assays in HeLa cells\",\n      \"pmids\": [\"20685960\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"In vivo physiological consequences of VPS51 loss in a whole organism were unknown\",\n        \"Whether VPS51 also participates in the related EARP complex was not addressed\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstration that C. elegans GARP mutants are viable but exhibit lysosomal morphology defects, and that GARP and COG have synthetic-lethal interactions, established overlapping but non-redundant roles for VPS51-containing GARP in retrograde trafficking across metazoa.\",\n      \"evidence\": \"Genetic deletion, electron microscopy of lysosomes, synthetic lethality screen in C. elegans\",\n      \"pmids\": [\"21613545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether VPS51 has tissue-specific roles, especially in the nervous system, was untested\",\n        \"Mechanism by which GARP and COG cooperate was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Discovery that compound heterozygous and homozygous loss-of-function VPS51 mutations cause a severe human neurodevelopmental disorder demonstrated that VPS51 is essential for brain development; patient cells showed reduced GARP/EARP assembly, mislocalization of CI-M6PR, and lysosomal swelling, directly linking human disease to the retrograde trafficking mechanism.\",\n      \"evidence\": \"Exome sequencing in affected families, Co-IP of complex assembly, immunofluorescence of receptor and lysosome markers in patient fibroblasts\",\n      \"pmids\": [\"30624672\", \"31207318\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How partial VPS51 loss preferentially affects neuronal versus other cell types is unclear\",\n        \"Relative contributions of GARP versus EARP dysfunction to pathology are not separated\",\n        \"No animal model recapitulating the human neurodevelopmental phenotype has been reported\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which VPS51 dysfunction selectively disrupts brain development despite ubiquitous expression, and whether therapeutic restoration of GARP/EARP complex assembly can rescue the phenotype, remain open questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No neuron-specific functional studies of VPS51 loss exist\",\n        \"No high-resolution structure of the full mammalian GARP complex including VPS51 is available\",\n        \"Whether VPS51 has GARP-independent functions has not been tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 2, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2, 3, 4]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"complexes\": [\n      \"GARP complex\",\n      \"EARP complex\"\n    ],\n    \"partners\": [\n      \"VPS52\",\n      \"VPS53\",\n      \"VPS54\",\n      \"STX6\",\n      \"TLG1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"VPS51 is a shared subunit of two heterotetrameric membrane-tethering complexes — GARP (with VPS52, VPS53, VPS54) at the trans-Golgi network and EARP (with VPS52, VPS53, syndetin) at recycling endosomes — that promote SNARE-dependent fusion of endosome-derived transport carriers [PMID:12446664, PMID:25799061]. VPS51 assembles into these complexes via a conserved N-terminal coiled-coil that also engages TGN SNAREs (Syntaxin 6 in mammals; Tlg1 in yeast), thereby coordinating tethering with fusion-competent SNARE complex formation [PMID:16420526, PMID:20685960]. Through GARP, VPS51 supports retrograde endosome-to-Golgi retrieval of cargo such as the cation-independent mannose 6-phosphate receptor, endosomal cholesterol trafficking, lysosomal enzyme sorting, and autophagy; through EARP, it facilitates recycling of endocytic receptors to the plasma membrane [PMID:20685960, PMID:25799061]. Biallelic loss-of-function mutations in VPS51 cause a severe neurodevelopmental disorder with microcephaly, pontocerebellar abnormalities, epilepsy, and lysosomal dysfunction, linked to impaired GARP/EARP complex assembly and defective retrograde trafficking [PMID:30624672, PMID:31207318].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Identification of Vps51 as the fourth subunit of the yeast VFT/GARP tethering complex established that retrograde endosome-to-Golgi transport and autophagosome biogenesis require a dedicated tethering factor beyond Vps52–54.\",\n      \"evidence\": \"Genetic deletion, reciprocal co-IP, fluorescence microscopy, and prApe1 maturation assays in S. cerevisiae\",\n      \"pmids\": [\"12446664\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural information on Vps51 or its contacts within the GARP complex\",\n        \"Mechanism by which Vps51 contributes to autophagosome size regulation unknown\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"A crystal structure of the Tlg1 N-terminal domain bound to a Vps51 peptide revealed the molecular basis for SNARE engagement but showed this interaction is dispensable for retrograde transport, raising the question of what other tethering contacts are essential.\",\n      \"evidence\": \"X-ray crystallography of Tlg1–Vps51 peptide complex; in vivo trafficking assays with Vps51 truncation mutants in yeast\",\n      \"pmids\": [\"16420526\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Essential Vps51 domains for vesicle docking and fusion remain unidentified\",\n        \"No structure of full-length Vps51 or intact GARP complex\"\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstration that human Ang2/VPS51 is the missing fourth subunit of mammalian GARP extended the complex to metazoans and connected it to Syntaxin 6 engagement, lysosomal enzyme sorting, cholesterol trafficking, and autophagy.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP, biochemical fractionation, siRNA knockdown with CI-MPR, filipin, and LC3 flux assays in human cells\",\n      \"pmids\": [\"20685960\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Relative contributions of GARP versus other tethers to each trafficking pathway not delineated\",\n        \"Whether VPS51 has functions independent of the GARP complex was untested\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Genetic analysis in C. elegans showed GARP (including Vps51) is conserved in metazoans and functionally overlaps with the COG complex, establishing redundancy among Golgi-resident tethers.\",\n      \"evidence\": \"Genetic deletion/RNAi, yeast two-hybrid SNARE binding, lysosome morphology, and synthetic lethality with COG mutants in C. elegans\",\n      \"pmids\": [\"21613545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of GARP–COG functional overlap not resolved\",\n        \"Tissue-specific requirements for Vps51 in multicellular organisms unexplored\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Discovery of the EARP complex revealed that VPS51 is shared between two functionally distinct tethering complexes — GARP at the TGN and EARP at recycling endosomes — with the differential fourth subunit (VPS54 vs. syndetin) dictating localization and cargo specificity.\",\n      \"evidence\": \"AP-MS, reciprocal co-IP, confocal immunofluorescence, and transferrin recycling assays with siRNA knockdown in human cells\",\n      \"pmids\": [\"25799061\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which VPS51 switches between GARP and EARP assembly is unknown\",\n        \"Structural basis for EARP-specific localization to recycling endosomes not determined\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identification of biallelic VPS51 mutations in patients with severe neurodevelopmental disease, supported by impaired GARP/EARP assembly and retrograde trafficking defects in patient cells, established VPS51 as a disease gene and demonstrated that both complexes are required for normal brain development.\",\n      \"evidence\": \"Exome sequencing, proteasome inhibitor rescue of mutant protein, co-IP for complex assembly, CI-MPR and lysosome morphology in patient fibroblasts; independent family with homozygous deletion confirmed by homozygosity mapping\",\n      \"pmids\": [\"30624672\", \"31207318\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Cell-type-specific contributions (neuronal vs. glial) of VPS51 loss to brain malformation not resolved\",\n        \"Whether residual EARP function partially compensates for GARP loss (or vice versa) in patient cells is unknown\",\n        \"No animal model recapitulating the full human phenotype has been reported\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the structural basis of the intact GARP and EARP complexes, the mechanism governing VPS51 partitioning between GARP and EARP, and the neuron-specific pathways through which VPS51 deficiency leads to pontocerebellar hypoplasia.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of full-length VPS51 or assembled GARP/EARP complexes\",\n        \"Regulatory mechanisms controlling VPS51 allocation between GARP and EARP are unknown\",\n        \"Neuron-type-specific vulnerability to VPS51 loss not characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 4, 5]}\n    ],\n    \"complexes\": [\n      \"GARP (VPS51–VPS52–VPS53–VPS54)\",\n      \"EARP (VPS51–VPS52–VPS53–syndetin)\"\n    ],\n    \"partners\": [\n      \"VPS52\",\n      \"VPS53\",\n      \"VPS54\",\n      \"SYNDETIN\",\n      \"STX6\",\n      \"TLG1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}