{"gene":"TG_230140","gene_symbol":"VPS9","run_date":"2026-09-08T11:06:49","timeline":{"discoveries":[{"year":2016,"finding":"TgVps9 functions as a guanine nucleotide exchange factor (GEF) towards Rab5a in Toxoplasma gondii, activating Rab5a to facilitate vesicular trafficking to secretory organelles.","method":"GEF activity assay (biochemical assay demonstrating nucleotide exchange activity towards Rab5a)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical GEF activity assay in a single lab study with functional follow-up on organelle biogenesis","pmids":["27966671"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"TgVps9 is required for correct sorting of proteins to rhoptries, micronemes, and dense granules, as loss of TgVps9 disrupts protein maturation and secretory organelle formation.","method":"Loss-of-function genetic analysis with phenotypic readout of secretory organelle biogenesis and protein sorting","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function approach with defined cellular phenotype (organelle biogenesis defect), single lab","pmids":["27966671"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"finding":"TgVps9 plays a critical role in host cell infection by T. gondii, acting as a key trafficking facilitator that regulates secretion from secretory organelles.","method":"Loss-of-function genetic analysis with host infection assay","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined loss-of-function phenotype (impaired host infection), single lab, single study","pmids":["27966671"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgVps9 acts as a guanine nucleotide exchange factor (GEF) for Rab5a and is essential for vesicular trafficking that sorts proteins to the three secretory organelles (rhoptries, micronemes, and dense granules), thereby regulating organelle biogenesis, protein maturation, and secretion required for host cell invasion by Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"TgVps9 is a guanine nucleotide exchange factor (GEF) that governs vesicular trafficking to the secretory organelles of Toxoplasma gondii, thereby supporting the parasite's ability to invade host cells [PMID:27966671]. Biochemically, it activates Rab5a by catalyzing nucleotide exchange, coupling this GTPase to trafficking toward the secretory organelles [PMID:27966671]. Functionally, loss of TgVps9 disrupts protein maturation and biogenesis of rhoptries, micronemes, and dense granules, producing defects in the correct sorting of proteins to these organelles [PMID:27966671] and impairing secretion required for host cell infection [PMID:27966671]. Beyond this Rab5a-dependent trafficking role in T. gondii, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Establishing the biochemical activity of TgVps9 answered whether it is a catalytic regulator of Rab GTPase signaling: it was shown to be a GEF that activates Rab5a, defining the molecular reaction it drives in secretory trafficking.","evidence":"in vitro GEF activity assay measuring nucleotide exchange toward Rab5a in Toxoplasma gondii","pmids":["27966671"],"confidence":"Medium","gaps":["Structural basis of the TgVps9-Rab5a interaction not resolved","Whether TgVps9 acts on Rab GTPases other than Rab5a not tested","Kinetics and specificity of exchange not quantified against other candidate substrates"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"Loss-of-function analysis connected TgVps9 GEF activity to organelle biology, showing it is required for correct protein sorting to and biogenesis of rhoptries, micronemes, and dense granules.","evidence":"genetic loss-of-function with phenotypic readout of secretory organelle biogenesis and protein maturation in T. gondii","pmids":["27966671"],"confidence":"Medium","gaps":["Which cargo proteins depend directly on TgVps9-mediated trafficking not delineated","Whether the sorting defect is a direct consequence of impaired Rab5a activation not dissected","Subcellular site of TgVps9 action within the endosomal/secretory pathway not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2016,"claim":"Host infection assays established the physiological consequence of TgVps9 function, showing it is a critical trafficking facilitator required for secretion and host cell invasion.","evidence":"loss-of-function genetic analysis coupled to host infection assay in T. gondii","pmids":["27966671"],"confidence":"Medium","gaps":["Contribution of individual organelle defects to the invasion phenotype not separated","In vivo relevance beyond cultured host cell infection not assessed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether TgVps9 has additional Rab substrates, defined domain determinants of its GEF activity, or a resolved localization within the endosomal-secretory pathway remains unaddressed in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or domain-level characterization of TgVps9","No interactome beyond Rab5a","No independent-lab replication of the GEF and phenotypic findings"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RAB5A"],"other_free_text":["Required for biogenesis of and protein sorting to rhoptries, micronemes, and dense granules [#1]","Loss impairs secretion and host cell infection by T. gondii [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"27966671","id":"PMC_27966671","title":"A Critical Role for Toxoplasma gondii Vacuolar Protein Sorting VPS9 in Secretory Organelle Biogenesis and Host Infection.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27966671","citation_count":27,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2810,"output_tokens":723,"usd":0.009638,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5484,"output_tokens":1763,"usd":0.035748,"stage2_stop_reason":"end_turn"},"total_usd":0.045386,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"TgVps9 functions as a guanine nucleotide exchange factor (GEF) towards Rab5a in Toxoplasma gondii, activating Rab5a to facilitate vesicular trafficking to secretory organelles.\",\n      \"method\": \"GEF activity assay (biochemical assay demonstrating nucleotide exchange activity towards Rab5a)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical GEF activity assay in a single lab study with functional follow-up on organelle biogenesis\",\n      \"pmids\": [\"27966671\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TgVps9 is required for correct sorting of proteins to rhoptries, micronemes, and dense granules, as loss of TgVps9 disrupts protein maturation and secretory organelle formation.\",\n      \"method\": \"Loss-of-function genetic analysis with phenotypic readout of secretory organelle biogenesis and protein sorting\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function approach with defined cellular phenotype (organelle biogenesis defect), single lab\",\n      \"pmids\": [\"27966671\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TgVps9 plays a critical role in host cell infection by T. gondii, acting as a key trafficking facilitator that regulates secretion from secretory organelles.\",\n      \"method\": \"Loss-of-function genetic analysis with host infection assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined loss-of-function phenotype (impaired host infection), single lab, single study\",\n      \"pmids\": [\"27966671\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgVps9 acts as a guanine nucleotide exchange factor (GEF) for Rab5a and is essential for vesicular trafficking that sorts proteins to the three secretory organelles (rhoptries, micronemes, and dense granules), thereby regulating organelle biogenesis, protein maturation, and secretion required for host cell invasion by Toxoplasma gondii.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgVps9 is a guanine nucleotide exchange factor (GEF) that governs vesicular trafficking to the secretory organelles of Toxoplasma gondii, thereby supporting the parasite's ability to invade host cells [#0, #2]. Biochemically, it activates Rab5a by catalyzing nucleotide exchange, coupling this GTPase to trafficking toward the secretory organelles [#0]. Functionally, loss of TgVps9 disrupts protein maturation and biogenesis of rhoptries, micronemes, and dense granules, producing defects in the correct sorting of proteins to these organelles [#1] and impairing secretion required for host cell infection [#2]. Beyond this Rab5a-dependent trafficking role in T. gondii, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing the biochemical activity of TgVps9 answered whether it is a catalytic regulator of Rab GTPase signaling: it was shown to be a GEF that activates Rab5a, defining the molecular reaction it drives in secretory trafficking.\",\n      \"evidence\": \"in vitro GEF activity assay measuring nucleotide exchange toward Rab5a in Toxoplasma gondii\",\n      \"pmids\": [\"27966671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of the TgVps9-Rab5a interaction not resolved\",\n        \"Whether TgVps9 acts on Rab GTPases other than Rab5a not tested\",\n        \"Kinetics and specificity of exchange not quantified against other candidate substrates\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Loss-of-function analysis connected TgVps9 GEF activity to organelle biology, showing it is required for correct protein sorting to and biogenesis of rhoptries, micronemes, and dense granules.\",\n      \"evidence\": \"genetic loss-of-function with phenotypic readout of secretory organelle biogenesis and protein maturation in T. gondii\",\n      \"pmids\": [\"27966671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Which cargo proteins depend directly on TgVps9-mediated trafficking not delineated\",\n        \"Whether the sorting defect is a direct consequence of impaired Rab5a activation not dissected\",\n        \"Subcellular site of TgVps9 action within the endosomal/secretory pathway not mapped\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Host infection assays established the physiological consequence of TgVps9 function, showing it is a critical trafficking facilitator required for secretion and host cell invasion.\",\n      \"evidence\": \"loss-of-function genetic analysis coupled to host infection assay in T. gondii\",\n      \"pmids\": [\"27966671\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Contribution of individual organelle defects to the invasion phenotype not separated\",\n        \"In vivo relevance beyond cultured host cell infection not assessed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TgVps9 has additional Rab substrates, defined domain determinants of its GEF activity, or a resolved localization within the endosomal-secretory pathway remains unaddressed in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or domain-level characterization of TgVps9\",\n        \"No interactome beyond Rab5a\",\n        \"No independent-lab replication of the GEF and phenotypic findings\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005085\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0007264\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"Rab5a\"],\n    \"other_free_text\": [\n      \"Required for biogenesis of and protein sorting to rhoptries, micronemes, and dense granules [#1]\",\n      \"Loss impairs secretion and host cell infection by T. gondii [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_230140","name":"VPS9","product":"vacuolar protein sorting-associated protein 9","uniprot_acc":"A0A125YVE6","chromosome":"TGME49_chrVIII","start_pos":632417},{"strain":"GT1","gene_id":"TGGT1_230140","name":null,"product":"vacuolar sorting protein 9 (vps9) domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":629820},{"strain":"RH88","gene_id":"TGRH88_074640","name":null,"product":"vacuolar sorting protein 9 (vps9) domain-containing protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":5741261},{"strain":"VEG","gene_id":"TGVEG_230140","name":null,"product":"vacuolar sorting protein 9 (vps9) domain-containing protein","uniprot_acc":"B6KJB2","chromosome":"TGVEG_chrVIII","start_pos":639492}]}