{"gene":"TG_223920","gene_symbol":"RON3","run_date":"2026-09-08T11:06:41","timeline":{"discoveries":[{"year":2011,"finding":"The Plasmodium falciparum ortholog of TgRON3 (PfRON3) localizes to the rhoptry body (not the rhoptry neck) in merozoites, and co-immunoprecipitation showed it interacts with PfRON2 and PfRON4 but not with PfAMA1, suggesting it forms a novel RON complex (PfRON2/3/4) distinct from the moving junction complex.","method":"Immunofluorescence microscopy, immunoelectron microscopy, co-immunoprecipitation","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP with subcellular localization by IEM, single lab; findings are in P. falciparum (ortholog), not directly in T. gondii","pmids":["21237287"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PfRON3 (ortholog of TgRON3) localizes to the rhoptry bulb of P. falciparum merozoites, binds directly to erythrocytes as a recombinant protein, and anti-PfRON3 antibodies significantly inhibit merozoite invasion into erythrocytes, indicating a functional role in host-cell entry.","method":"Immunoelectron microscopy, IFA, erythrocyte-binding assay with recombinant protein, invasion inhibition assay with specific antibodies","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (IEM, binding assay, functional inhibition), single lab; findings are in P. falciparum (ortholog), not directly in T. gondii","pmids":["25495792"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"In Chinese 1 T. gondii strains of differing virulence (Wh3 vs. Wh6), RON3 harbors 89 SNPs and 6 indels relative to the GT1 reference genome, and RON3 transcript levels are higher in the less virulent Wh6 strain than in the virulent Wh3 strain.","method":"Next-generation whole-genome sequencing and qRT-PCR expression analysis","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — genomic/expression data only, no direct functional or mechanistic experiment on RON3 protein itself","pmids":["26518334"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"Chinese 1 (Wh3, Wh6)"}]}],"current_model":"TgRON3 is a rhoptry protein in Toxoplasma gondii; mechanistic insight is largely inferred from its well-characterized P. falciparum ortholog (PfRON3), which resides in the rhoptry body, participates in a novel RON2/3/4 complex distinct from the AMA1-associated moving junction complex, and contributes to erythrocyte invasion, while in T. gondii itself only genomic variation and differential expression data are available with no direct mechanistic experiments reported in this corpus."},"narrative":{"mechanistic_narrative":"RON3 is a rhoptry protein implicated in apicomplexan host-cell invasion, characterized mechanistically through its Plasmodium falciparum ortholog PfRON3. PfRON3 localizes to the rhoptry body/bulb rather than the rhoptry neck in merozoites, and reciprocal co-immunoprecipitation places it in a novel RON2/3/4 complex that does not include AMA1, distinguishing it from the AMA1-associated moving junction complex [PMID:21237287]. Recombinant PfRON3 binds directly to erythrocytes, and anti-PfRON3 antibodies inhibit merozoite invasion, establishing a functional role in host-cell entry [PMID:25495792]. In Toxoplasma gondii itself, only genomic variation and differential expression data are available: RON3 carries strain-specific SNPs and indels and is expressed more highly in the less virulent Wh6 strain than in the virulent Wh3 strain [PMID:26518334]. No direct mechanistic experiments on TgRON3 protein are reported in the available corpus.","teleology":[{"year":2011,"claim":"Establishing that PfRON3 defines a rhoptry-body RON complex separate from the moving junction answered whether all RON proteins act through the AMA1-linked junction, revealing a distinct RON2/3/4 assembly.","evidence":"Immunofluorescence, immunoelectron microscopy, and reciprocal co-IP in P. falciparum merozoites","pmids":["21237287"],"confidence":"Medium","gaps":["Functional consequence of the RON2/3/4 complex not tested","Findings in P. falciparum ortholog, not directly in T. gondii","Stoichiometry and assembly order of the complex undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Direct erythrocyte binding by recombinant PfRON3 and antibody-mediated invasion inhibition addressed whether the protein participates functionally in host-cell entry, confirming a role in invasion.","evidence":"IEM, IFA, recombinant erythrocyte-binding assay, and invasion inhibition with specific antibodies in P. falciparum","pmids":["25495792"],"confidence":"Medium","gaps":["Erythrocyte receptor for PfRON3 not identified","Mechanistic link between binding and junction formation unresolved","No orthologous validation in T. gondii"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Cataloguing RON3 sequence variation and expression differences across virulence-divergent T. gondii strains raised the question of whether RON3 contributes to strain virulence, showing an inverse correlation between transcript level and virulence.","evidence":"Whole-genome sequencing and qRT-PCR of Chinese 1 T. gondii strains Wh3 and Wh6","pmids":["26518334"],"confidence":"Low","gaps":["Correlational only — no functional or mechanistic experiment on the RON3 protein","Causal contribution of the SNPs/indels to virulence untested","TgRON3 localization and interaction partners not experimentally determined"],"attribution":[{"species":"Toxoplasma gondii","strain":"Chinese 1 (Wh3, Wh6)"}]},{"year":null,"claim":"Whether TgRON3 forms an equivalent RON2/3/4 complex, localizes to the rhoptry body, and functions in T. gondii host-cell invasion remains unestablished by direct experiment.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct localization of TgRON3 protein reported","No interaction partners defined in T. gondii","No invasion or knockout phenotype for TgRON3"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RON2/3/4 complex (PfRON2/PfRON3/PfRON4), distinct from the AMA1-associated moving junction complex [#0]"],"partners":["PFRON2 [#0]","PFRON4 [#0]","DOES NOT INTERACT WITH PFAMA1 [#0]"],"other_free_text":["PfRON3 binds directly to erythrocytes as a recombinant protein, and anti-PfRON3 antibodies inhibit merozoite invasion [#1]","In T. gondii, RON3 shows strain-specific SNPs/indels and higher transcript levels in the less virulent Wh6 strain than the virulent Wh3 strain [#2]","All mechanistic characterization derives from the P. falciparum ortholog; no direct functional experiments on TgRON3 protein are reported in the corpus"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"26518334","id":"PMC_26518334","title":"Variation detection based on next-generation sequencing of type Chinese 1 strains of Toxoplasma gondii with different virulence from China.","date":"2015","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/26518334","citation_count":55,"is_preprint":false},{"pmid":"21237287","id":"PMC_21237287","title":"Plasmodial ortholog of Toxoplasma gondii rhoptry neck protein 3 is localized to the rhoptry body.","date":"2011","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/21237287","citation_count":33,"is_preprint":false},{"pmid":"25495792","id":"PMC_25495792","title":"PfRON3 is an erythrocyte-binding protein and a potential blood-stage vaccine candidate antigen.","date":"2014","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/25495792","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4503,"output_tokens":968,"usd":0.014014,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5767,"output_tokens":2043,"usd":0.039955,"stage2_stop_reason":"end_turn"},"total_usd":0.053969,"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\": 2011,\n      \"finding\": \"The Plasmodium falciparum ortholog of TgRON3 (PfRON3) localizes to the rhoptry body (not the rhoptry neck) in merozoites, and co-immunoprecipitation showed it interacts with PfRON2 and PfRON4 but not with PfAMA1, suggesting it forms a novel RON complex (PfRON2/3/4) distinct from the moving junction complex.\",\n      \"method\": \"Immunofluorescence microscopy, immunoelectron microscopy, co-immunoprecipitation\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP with subcellular localization by IEM, single lab; findings are in P. falciparum (ortholog), not directly in T. gondii\",\n      \"pmids\": [\"21237287\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PfRON3 (ortholog of TgRON3) localizes to the rhoptry bulb of P. falciparum merozoites, binds directly to erythrocytes as a recombinant protein, and anti-PfRON3 antibodies significantly inhibit merozoite invasion into erythrocytes, indicating a functional role in host-cell entry.\",\n      \"method\": \"Immunoelectron microscopy, IFA, erythrocyte-binding assay with recombinant protein, invasion inhibition assay with specific antibodies\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (IEM, binding assay, functional inhibition), single lab; findings are in P. falciparum (ortholog), not directly in T. gondii\",\n      \"pmids\": [\"25495792\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In Chinese 1 T. gondii strains of differing virulence (Wh3 vs. Wh6), RON3 harbors 89 SNPs and 6 indels relative to the GT1 reference genome, and RON3 transcript levels are higher in the less virulent Wh6 strain than in the virulent Wh3 strain.\",\n      \"method\": \"Next-generation whole-genome sequencing and qRT-PCR expression analysis\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — genomic/expression data only, no direct functional or mechanistic experiment on RON3 protein itself\",\n      \"pmids\": [\"26518334\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"Chinese 1 (Wh3, Wh6)\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgRON3 is a rhoptry protein in Toxoplasma gondii; mechanistic insight is largely inferred from its well-characterized P. falciparum ortholog (PfRON3), which resides in the rhoptry body, participates in a novel RON2/3/4 complex distinct from the AMA1-associated moving junction complex, and contributes to erythrocyte invasion, while in T. gondii itself only genomic variation and differential expression data are available with no direct mechanistic experiments reported in this corpus.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RON3 is a rhoptry protein implicated in apicomplexan host-cell invasion, characterized mechanistically through its Plasmodium falciparum ortholog PfRON3. PfRON3 localizes to the rhoptry body/bulb rather than the rhoptry neck in merozoites, and reciprocal co-immunoprecipitation places it in a novel RON2/3/4 complex that does not include AMA1, distinguishing it from the AMA1-associated moving junction complex [#0]. Recombinant PfRON3 binds directly to erythrocytes, and anti-PfRON3 antibodies inhibit merozoite invasion, establishing a functional role in host-cell entry [#1]. In Toxoplasma gondii itself, only genomic variation and differential expression data are available: RON3 carries strain-specific SNPs and indels and is expressed more highly in the less virulent Wh6 strain than in the virulent Wh3 strain [#2]. No direct mechanistic experiments on TgRON3 protein are reported in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Establishing that PfRON3 defines a rhoptry-body RON complex separate from the moving junction answered whether all RON proteins act through the AMA1-linked junction, revealing a distinct RON2/3/4 assembly.\",\n      \"evidence\": \"Immunofluorescence, immunoelectron microscopy, and reciprocal co-IP in P. falciparum merozoites\",\n      \"pmids\": [\"21237287\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the RON2/3/4 complex not tested\", \"Findings in P. falciparum ortholog, not directly in T. gondii\", \"Stoichiometry and assembly order of the complex undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Direct erythrocyte binding by recombinant PfRON3 and antibody-mediated invasion inhibition addressed whether the protein participates functionally in host-cell entry, confirming a role in invasion.\",\n      \"evidence\": \"IEM, IFA, recombinant erythrocyte-binding assay, and invasion inhibition with specific antibodies in P. falciparum\",\n      \"pmids\": [\"25495792\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Erythrocyte receptor for PfRON3 not identified\", \"Mechanistic link between binding and junction formation unresolved\", \"No orthologous validation in T. gondii\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Cataloguing RON3 sequence variation and expression differences across virulence-divergent T. gondii strains raised the question of whether RON3 contributes to strain virulence, showing an inverse correlation between transcript level and virulence.\",\n      \"evidence\": \"Whole-genome sequencing and qRT-PCR of Chinese 1 T. gondii strains Wh3 and Wh6\",\n      \"pmids\": [\"26518334\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Correlational only \\u2014 no functional or mechanistic experiment on the RON3 protein\", \"Causal contribution of the SNPs/indels to virulence untested\", \"TgRON3 localization and interaction partners not experimentally determined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"Chinese 1 (Wh3, Wh6)\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TgRON3 forms an equivalent RON2/3/4 complex, localizes to the rhoptry body, and functions in T. gondii host-cell invasion remains unestablished by direct experiment.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct localization of TgRON3 protein reported\", \"No interaction partners defined in T. gondii\", \"No invasion or knockout phenotype for TgRON3\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0034987\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020008\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"RON2/3/4 complex (PfRON2/PfRON3/PfRON4), distinct from the AMA1-associated moving junction complex [#0]\"\n    ],\n    \"partners\": [\n      \"PfRON2 [#0]\",\n      \"PfRON4 [#0]\",\n      \"does not interact with PfAMA1 [#0]\"\n    ],\n    \"other_free_text\": [\n      \"PfRON3 binds directly to erythrocytes as a recombinant protein, and anti-PfRON3 antibodies inhibit merozoite invasion [#1]\",\n      \"In T. gondii, RON3 shows strain-specific SNPs/indels and higher transcript levels in the less virulent Wh6 strain than the virulent Wh3 strain [#2]\",\n      \"All mechanistic characterization derives from the P. falciparum ortholog; no direct functional experiments on TgRON3 protein are reported in the corpus\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_223920","name":"RON3","product":"rhoptry neck protein RON3","uniprot_acc":"S8EX30","chromosome":"TGME49_chrX","start_pos":3452984},{"strain":"GT1","gene_id":"TGGT1_223920","name":null,"product":"rhoptry neck protein RON3","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":3357300},{"strain":"RH88","gene_id":"TGRH88_043710","name":null,"product":"rhoptry neck protein RON3","uniprot_acc":null,"chromosome":"CM023091","start_pos":4100680},{"strain":"VEG","gene_id":"TGVEG_223920","name":null,"product":"rhoptry neck protein RON3","uniprot_acc":"V4YW47","chromosome":"TGVEG_chrX","start_pos":3356952}]}