{"gene":"TG_261750","gene_symbol":"RON10","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2012,"finding":"RON9 and RON10 form a high molecular mass complex localized to the rhoptry neck in Toxoplasma gondii, distinct from the moving junction complex (RON2/4/5/8); the complex was not detected at the moving junction during invasion.","method":"Biochemical fractionation, co-immunoprecipitation, immunofluorescence/immunoelectron microscopy","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and localization with functional invasion assays in a single focused study","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"finding":"Disruption of either RON9 or RON10 causes retention of the partner protein in the ER followed by its degradation, demonstrating that RON9/RON10 complex formation is required for proper sorting to the rhoptries.","method":"Gene disruption (knockout), immunofluorescence microscopy, Western blot","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic knockouts with specific subcellular localization and stability readouts, multiple orthogonal methods in one study","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"finding":"Absence of RON9/RON10 has no significant impact on rhoptry morphology, host cell invasion, or parasite growth in fibroblasts in vitro, or on virulence in vivo.","method":"Gene disruption (knockout), invasion and growth assays, mouse virulence model","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — negative result from clean KO but single lab, single study","pmids":["22427839"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"RON10 forms a high-molecular-mass complex with RON9 in the rhoptry neck of Toxoplasma gondii; the two proteins are mutually dependent for ER exit and trafficking to the rhoptries, but the RON9/RON10 complex is not part of the moving junction and is dispensable for host cell invasion and growth in fibroblasts in vitro, suggesting a role specific to development in intestinal epithelial cells."},"narrative":{"mechanistic_narrative":"RON10 is a rhoptry neck protein of Toxoplasma gondii that partners with RON9 to form a high-molecular-mass complex distinct from the moving junction complex (RON2/4/5/8) and not detectable at the moving junction during invasion [PMID:22427839]. RON9 and RON10 are mutually dependent: disruption of either protein causes retention of its partner in the ER and subsequent degradation, establishing that complex formation is required for ER exit and proper sorting to the rhoptries [PMID:22427839]. Loss of the RON9/RON10 complex has no significant effect on rhoptry morphology, host cell invasion, parasite growth in fibroblasts, or virulence in mice, indicating that the complex is dispensable for the canonical lytic cycle in vitro [PMID:22427839]. Beyond these findings, no further mechanistic role for RON10 has been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing that RON10 resides in the rhoptry neck as part of a discrete RON9/RON10 complex separated the protein from the known moving junction machinery and defined a new rhoptry neck sub-complex.","evidence":"Biochemical fractionation, reciprocal co-immunoprecipitation, and immunofluorescence/immunoelectron microscopy in Toxoplasma gondii","pmids":["22427839"],"confidence":"High","gaps":["No molecular function or enzymatic/binding activity assigned to RON10 itself","Stoichiometry and additional members of the complex not defined","Reason the complex is excluded from the moving junction unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"claim":"Knockout of either partner revealed a mutual dependency for ER exit and rhoptry targeting, showing that RON9/RON10 complex assembly is a prerequisite for proper trafficking rather than the proteins being independently sorted.","evidence":"Gene disruption of RON9 or RON10 with immunofluorescence and Western blot readouts of localization and stability in Toxoplasma gondii","pmids":["22427839"],"confidence":"High","gaps":["Molecular basis of the ER-retention/degradation of the orphaned partner unknown","Trafficking machinery mediating rhoptry sorting of the complex not identified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2012,"claim":"Phenotyping the knockouts showed the complex is dispensable for invasion, growth, and virulence in standard models, narrowing its likely functional relevance to contexts not captured by fibroblast infection or acute mouse virulence.","evidence":"Invasion and growth assays plus a mouse virulence model on RON9/RON10 knockouts in Toxoplasma gondii","pmids":["22427839"],"confidence":"Medium","gaps":["Negative result from a single lab/single study","No functional assay in intestinal epithelial or developmental (sexual/enteric) stages where a role is hypothesized","No condition identified in which loss of the complex produces a phenotype"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biological process in which the RON9/RON10 complex actually functions, and RON10's molecular activity within it, remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No stage- or tissue-specific phenotype demonstrated for the complex","No molecular function or interaction beyond RON9 established for RON10","No structural or mechanistic model of complex assembly or trafficking"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RON9/RON10 high-molecular-mass rhoptry neck complex"],"partners":["RON9"],"other_free_text":["RON9/RON10 complex is distinct from the moving junction complex (RON2/RON4/RON5/RON8) and not detected at the moving junction during invasion [#0].","RON9 and RON10 are mutually dependent for ER exit and rhoptry targeting; loss of one leads to ER retention and degradation of the other [#1].","Complex is dispensable for rhoptry morphology, invasion, in vitro growth in fibroblasts, and mouse virulence [#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},{"pmid":"28979342","id":"PMC_28979342","title":"Sequence Variation in Rhoptry Neck Protein 10 Gene among Toxoplasma gondii Isolates from Different Hosts and Geographical Locations.","date":"2017","source":"Iranian journal of parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/28979342","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3992,"output_tokens":742,"usd":0.011553,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5496,"output_tokens":2057,"usd":0.039453,"stage2_stop_reason":"end_turn"},"total_usd":0.051006,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","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 localized to the rhoptry neck in Toxoplasma gondii, distinct from the moving junction complex (RON2/4/5/8); the complex was not detected at the moving junction during invasion.\",\n      \"method\": \"Biochemical fractionation, co-immunoprecipitation, immunofluorescence/immunoelectron microscopy\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and localization with functional invasion assays in a single focused study\",\n      \"pmids\": [\"22427839\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Disruption of either RON9 or RON10 causes retention of the partner protein in the ER followed by its degradation, demonstrating that RON9/RON10 complex formation is required for proper sorting to the rhoptries.\",\n      \"method\": \"Gene disruption (knockout), immunofluorescence microscopy, Western blot\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockouts with specific subcellular localization and stability readouts, multiple orthogonal methods in one study\",\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, host cell invasion, or parasite growth in fibroblasts in vitro, or on virulence in vivo.\",\n      \"method\": \"Gene disruption (knockout), invasion and growth assays, mouse virulence model\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — negative result from clean KO but single lab, single study\",\n      \"pmids\": [\"22427839\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"RON10 forms a high-molecular-mass complex with RON9 in the rhoptry neck of Toxoplasma gondii; the two proteins are mutually dependent for ER exit and trafficking to the rhoptries, but the RON9/RON10 complex is not part of the moving junction and is dispensable for host cell invasion and growth in fibroblasts in vitro, suggesting a role specific to development in intestinal epithelial cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RON10 is a rhoptry neck protein of Toxoplasma gondii that partners with RON9 to form a high-molecular-mass complex distinct from the moving junction complex (RON2/4/5/8) and not detectable at the moving junction during invasion [#0]. RON9 and RON10 are mutually dependent: disruption of either protein causes retention of its partner in the ER and subsequent degradation, establishing that complex formation is required for ER exit and proper sorting to the rhoptries [#1]. Loss of the RON9/RON10 complex has no significant effect on rhoptry morphology, host cell invasion, parasite growth in fibroblasts, or virulence in mice, indicating that the complex is dispensable for the canonical lytic cycle in vitro [#2]. Beyond these findings, no further mechanistic role for RON10 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing that RON10 resides in the rhoptry neck as part of a discrete RON9/RON10 complex separated the protein from the known moving junction machinery and defined a new rhoptry neck sub-complex.\",\n      \"evidence\": \"Biochemical fractionation, reciprocal co-immunoprecipitation, and immunofluorescence/immunoelectron microscopy in Toxoplasma gondii\",\n      \"pmids\": [\n        \"22427839\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No molecular function or enzymatic/binding activity assigned to RON10 itself\",\n        \"Stoichiometry and additional members of the complex not defined\",\n        \"Reason the complex is excluded from the moving junction unresolved\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Knockout of either partner revealed a mutual dependency for ER exit and rhoptry targeting, showing that RON9/RON10 complex assembly is a prerequisite for proper trafficking rather than the proteins being independently sorted.\",\n      \"evidence\": \"Gene disruption of RON9 or RON10 with immunofluorescence and Western blot readouts of localization and stability in Toxoplasma gondii\",\n      \"pmids\": [\n        \"22427839\"\n      ],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of the ER-retention/degradation of the orphaned partner unknown\",\n        \"Trafficking machinery mediating rhoptry sorting of the complex not identified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Phenotyping the knockouts showed the complex is dispensable for invasion, growth, and virulence in standard models, narrowing its likely functional relevance to contexts not captured by fibroblast infection or acute mouse virulence.\",\n      \"evidence\": \"Invasion and growth assays plus a mouse virulence model on RON9/RON10 knockouts in Toxoplasma gondii\",\n      \"pmids\": [\n        \"22427839\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Negative result from a single lab/single study\",\n        \"No functional assay in intestinal epithelial or developmental (sexual/enteric) stages where a role is hypothesized\",\n        \"No condition identified in which loss of the complex produces a phenotype\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biological process in which the RON9/RON10 complex actually functions, and RON10's molecular activity within it, remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No stage- or tissue-specific phenotype demonstrated for the complex\",\n        \"No molecular function or interaction beyond RON9 established for RON10\",\n        \"No structural or mechanistic model of complex assembly or trafficking\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"rhoptry neck\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      },\n      {\n        \"term_id\": \"endoplasmic reticulum (upon partner loss)\",\n        \"supporting_discovery_ids\": [1],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"protein sorting/trafficking to rhoptries\",\n        \"supporting_discovery_ids\": [1],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"RON9/RON10 high-molecular-mass rhoptry neck complex\"\n    ],\n    \"partners\": [\n      \"RON9\"\n    ],\n    \"other_free_text\": [\n      \"RON9/RON10 complex is distinct from the moving junction complex (RON2/RON4/RON5/RON8) and not detected at the moving junction during invasion [#0].\",\n      \"RON9 and RON10 are mutually dependent for ER exit and rhoptry targeting; loss of one leads to ER retention and degradation of the other [#1].\",\n      \"Complex is dispensable for rhoptry morphology, invasion, in vitro growth in fibroblasts, and mouse virulence [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_261750","name":"RON10","product":"rhoptry neck protein RON10","uniprot_acc":"S8F7R7","chromosome":"TGME49_chrVIIb","start_pos":1545605},{"strain":"GT1","gene_id":"TGGT1_261750","name":null,"product":"rhoptry neck protein RON10","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":1521076},{"strain":"RH88","gene_id":"TGRH88_068960","name":null,"product":"rhoptry neck protein RON10","uniprot_acc":null,"chromosome":"CM023089","start_pos":1565888},{"strain":"VEG","gene_id":"TGVEG_261750","name":null,"product":"rhoptry neck protein RON10","uniprot_acc":"V5B8P5","chromosome":"TGVEG_chrVIIb","start_pos":1561753}]}