{"gene":"TG_308810","gene_symbol":"RON9","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2012,"finding":"RON9 and RON10 form a high molecular mass complex in the rhoptry neck of Toxoplasma gondii, and proper complex formation between RON9 and RON10 is required for their sorting to the rhoptries; disruption of either gene causes retention of the partner protein in the ER followed by its degradation.","method":"Gene disruption (knockout) of RON9 or RON10, followed by localization analysis showing ER retention and degradation of the partner protein","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal genetic knockouts with localization and stability readouts in a single lab, two orthogonal methods (disruption + localization/degradation assay)","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"finding":"The RON9/RON10 complex is not detected at the moving junction (MJ) during host cell invasion and is not associated with the MJ complex RON2/4/5/8, distinguishing it functionally from other RON proteins.","method":"Localization studies during invasion (immunofluorescence/imaging) showing absence of RON9/RON10 at the moving junction","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment during invasion, single lab, negative localization result validated by comparison with known MJ components","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"finding":"Absence of RON9/RON10 has no significant impact on rhoptry morphology, parasite invasion, or growth in fibroblasts in vitro, nor on virulence in vivo.","method":"Genetic knockout of RON9 or RON10 with phenotypic assays: rhoptry morphology, invasion assays, growth assays in fibroblasts, and in vivo virulence studies","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple phenotypic readouts from clean knockouts, single lab; finding is a robust negative result across several assays","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"RON9 localizes to the rhoptry neck of Toxoplasma gondii where it forms a high molecular mass complex with RON10; complex formation is required for proper ER exit and sorting of both proteins to the rhoptries, but the RON9/RON10 complex is excluded from the moving junction and is dispensable for host cell invasion, intracellular growth, and in vivo virulence under standard laboratory conditions."},"narrative":{"mechanistic_narrative":"RON9 is a rhoptry neck protein of Toxoplasma gondii that forms a high molecular mass complex with RON10, and this heterotypic association is the central determinant of its trafficking: proper complex formation is required for exit from the ER and sorting to the rhoptries, such that disruption of either partner leaves the other retained in the ER and subsequently degraded [PMID:22427839]. Unlike other RON proteins, the RON9/RON10 complex is excluded from the moving junction during host cell invasion and is not associated with the RON2/4/5/8 MJ complex, distinguishing it functionally from the invasion machinery [PMID:22427839]. Consistent with this exclusion, loss of RON9/RON10 has no detectable effect on rhoptry morphology, invasion, intracellular growth in fibroblasts, or in vivo virulence under standard laboratory conditions, so its functional contribution beyond mutual stabilization and rhoptry sorting is uncharacterized in the available corpus [PMID:22427839].","teleology":[{"year":2012,"claim":"Establishing where RON9 resides and how it reaches its destination answered whether it is a bona fide rhoptry neck protein and revealed that its trafficking is co-dependent on a partner, showing complex assembly gates ER exit and rhoptry sorting.","evidence":"Reciprocal gene knockouts of RON9 and RON10 with localization and protein-stability readouts in Toxoplasma gondii","pmids":["22427839"],"confidence":"Medium","gaps":["The molecular basis of complex formation and the sorting signal directing the complex to rhoptries are not defined","Whether additional partners participate in the high molecular mass complex is not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"claim":"Testing whether RON9/RON10 behaves like canonical RON proteins answered whether it participates in the moving junction, and its absence there separated it functionally from the invasion-associated RON2/4/5/8 complex.","evidence":"Immunofluorescence localization during host cell invasion compared with known moving junction components in Toxoplasma gondii","pmids":["22427839"],"confidence":"Medium","gaps":["The actual function served by a rhoptry neck complex excluded from the moving junction is unknown","No molecular interaction data excludes transient or context-specific MJ association"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"claim":"Phenotyping the knockouts answered whether RON9/RON10 is required for the parasite's lytic cycle, and the robust negative result established that the complex is dispensable for invasion, growth, and virulence under standard conditions.","evidence":"Rhoptry morphology, invasion, growth in fibroblasts, and in vivo virulence assays on RON9/RON10 knockouts in Toxoplasma gondii","pmids":["22427839"],"confidence":"Medium","gaps":["No non-standard host or environmental conditions were tested that might reveal a phenotype","The biological process the complex contributes to remains unidentified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular function of the RON9/RON10 complex remains unknown: no substrate, ligand, or process has been assigned beyond mutual stabilization and rhoptry sorting.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No functional role identified despite clear rhoptry neck localization","No conditions found under which RON9 loss produces a phenotype","Structure and interaction basis of the complex undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RON9/RON10 high molecular mass complex"],"partners":["RON10"],"other_free_text":["Complex formation between RON9 and RON10 is mutually required for ER exit, rhoptry sorting, and protein stability [#0].","The RON9/RON10 complex is excluded from the moving junction and not associated with the RON2/4/5/8 MJ complex [#1].","RON9/RON10 is dispensable for rhoptry morphology, invasion, intracellular growth, and in vivo virulence under standard laboratory conditions [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"22427839","id":"PMC_22427839","title":"Identification of a new rhoptry neck complex RON9/RON10 in the Apicomplexa parasite Toxoplasma gondii.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22427839","citation_count":18,"is_preprint":false},{"pmid":"40881926","id":"PMC_40881926","title":"In silico evaluation of Toxoplasma gondii rhoptry neck proteins (TgRONs) for potential immunogenic epitopes.","date":"2025","source":"EXCLI journal","url":"https://pubmed.ncbi.nlm.nih.gov/40881926","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3498,"output_tokens":824,"usd":0.011427,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5607,"output_tokens":1883,"usd":0.037555,"stage2_stop_reason":"end_turn"},"total_usd":0.048982,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"RON9 and RON10 form a high molecular mass complex in the rhoptry neck of Toxoplasma gondii, and proper complex formation between RON9 and RON10 is required for their sorting to the rhoptries; disruption of either gene causes retention of the partner protein in the ER followed by its degradation.\",\n      \"method\": \"Gene disruption (knockout) of RON9 or RON10, followed by localization analysis showing ER retention and degradation of the partner protein\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal genetic knockouts with localization and stability readouts in a single lab, two orthogonal methods (disruption + localization/degradation assay)\",\n      \"pmids\": [\"22427839\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The RON9/RON10 complex is not detected at the moving junction (MJ) during host cell invasion and is not associated with the MJ complex RON2/4/5/8, distinguishing it functionally from other RON proteins.\",\n      \"method\": \"Localization studies during invasion (immunofluorescence/imaging) showing absence of RON9/RON10 at the moving junction\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment during invasion, single lab, negative localization result validated by comparison with known MJ components\",\n      \"pmids\": [\"22427839\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Absence of RON9/RON10 has no significant impact on rhoptry morphology, parasite invasion, or growth in fibroblasts in vitro, nor on virulence in vivo.\",\n      \"method\": \"Genetic knockout of RON9 or RON10 with phenotypic assays: rhoptry morphology, invasion assays, growth assays in fibroblasts, and in vivo virulence studies\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple phenotypic readouts from clean knockouts, single lab; finding is a robust negative result across several assays\",\n      \"pmids\": [\"22427839\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RON9 localizes to the rhoptry neck of Toxoplasma gondii where it forms a high molecular mass complex with RON10; complex formation is required for proper ER exit and sorting of both proteins to the rhoptries, but the RON9/RON10 complex is excluded from the moving junction and is dispensable for host cell invasion, intracellular growth, and in vivo virulence under standard laboratory conditions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RON9 is a rhoptry neck protein of Toxoplasma gondii that forms a high molecular mass complex with RON10, and this heterotypic association is the central determinant of its trafficking: proper complex formation is required for exit from the ER and sorting to the rhoptries, such that disruption of either partner leaves the other retained in the ER and subsequently degraded [#0]. Unlike other RON proteins, the RON9/RON10 complex is excluded from the moving junction during host cell invasion and is not associated with the RON2/4/5/8 MJ complex, distinguishing it functionally from the invasion machinery [#1]. Consistent with this exclusion, loss of RON9/RON10 has no detectable effect on rhoptry morphology, invasion, intracellular growth in fibroblasts, or in vivo virulence under standard laboratory conditions, so its functional contribution beyond mutual stabilization and rhoptry sorting is uncharacterized in the available corpus [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing where RON9 resides and how it reaches its destination answered whether it is a bona fide rhoptry neck protein and revealed that its trafficking is co-dependent on a partner, showing complex assembly gates ER exit and rhoptry sorting.\",\n      \"evidence\": \"Reciprocal gene knockouts of RON9 and RON10 with localization and protein-stability readouts in Toxoplasma gondii\",\n      \"pmids\": [\"22427839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The molecular basis of complex formation and the sorting signal directing the complex to rhoptries are not defined\", \"Whether additional partners participate in the high molecular mass complex is not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Testing whether RON9/RON10 behaves like canonical RON proteins answered whether it participates in the moving junction, and its absence there separated it functionally from the invasion-associated RON2/4/5/8 complex.\",\n      \"evidence\": \"Immunofluorescence localization during host cell invasion compared with known moving junction components in Toxoplasma gondii\",\n      \"pmids\": [\"22427839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The actual function served by a rhoptry neck complex excluded from the moving junction is unknown\", \"No molecular interaction data excludes transient or context-specific MJ association\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Phenotyping the knockouts answered whether RON9/RON10 is required for the parasite's lytic cycle, and the robust negative result established that the complex is dispensable for invasion, growth, and virulence under standard conditions.\",\n      \"evidence\": \"Rhoptry morphology, invasion, growth in fibroblasts, and in vivo virulence assays on RON9/RON10 knockouts in Toxoplasma gondii\",\n      \"pmids\": [\"22427839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No non-standard host or environmental conditions were tested that might reveal a phenotype\", \"The biological process the complex contributes to remains unidentified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function of the RON9/RON10 complex remains unknown: no substrate, ligand, or process has been assigned beyond mutual stabilization and rhoptry sorting.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional role identified despite clear rhoptry neck localization\", \"No conditions found under which RON9 loss produces a phenotype\", \"Structure and interaction basis of the complex undefined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"rhoptry neck\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"endoplasmic reticulum (upon complex disruption)\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"rhoptry protein sorting / ER exit\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"RON9/RON10 high molecular mass complex\"],\n    \"partners\": [\"RON10\"],\n    \"other_free_text\": [\n      \"Complex formation between RON9 and RON10 is mutually required for ER exit, rhoptry sorting, and protein stability [#0].\",\n      \"The RON9/RON10 complex is excluded from the moving junction and not associated with the RON2/4/5/8 MJ complex [#1].\",\n      \"RON9/RON10 is dispensable for rhoptry morphology, invasion, intracellular growth, and in vivo virulence under standard laboratory conditions [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_308810","name":"RON9","product":"rhoptry neck protein RON9","uniprot_acc":"S8GD61","chromosome":"TGME49_chrXI","start_pos":274907},{"strain":"GT1","gene_id":"TGGT1_308810B","name":null,"product":"rhoptry neck protein RON9","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":240636},{"strain":"RH88","gene_id":"TGRH88_048500","name":null,"product":"rhoptry neck protein RON9","uniprot_acc":null,"chromosome":"CM023092","start_pos":315864},{"strain":"VEG","gene_id":"TGVEG_308810B","name":null,"product":"rhoptry neck protein RON9","uniprot_acc":"V4ZRL7","chromosome":"TGVEG_chrXI","start_pos":285145}]}