{"gene":"TG_267530","gene_symbol":"STX18","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2021,"finding":"TgStx18 localizes to the endoplasmic reticulum (ER) in Toxoplasma gondii, as determined by localization analysis of SNARE proteins.","method":"Fluorescence localization analysis (conditional ablation and imaging)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence (conditional ablation causing secretory system defects), single lab","pmids":["34340555"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Conditional ablation of TgStx18 (ER-residing SNARE) caused severe defects in the secretory system, establishing a functional role for TgStx18 in ER-to-Golgi vesicular trafficking.","method":"Conditional knockout with phenotypic readout of secretory system integrity","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockout with defined cellular phenotype, single lab, single primary method","pmids":["34340555"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"TgStx19 (a novel Qc-SNARE) localizes to the ER and acts as a binding partner of TgStx18, replacing the canonical Use1 partner found in other eukaryotes.","method":"Localization analysis and partner identification by SNARE dissection assay","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-localization and functional partnership inferred from localization and conditional ablation, single lab, no direct binding assay described in abstract","pmids":["34340555"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgStx18 is an ER-resident SNARE in Toxoplasma gondii that functions in the secretory vesicular trafficking pathway, partnering with a novel Qc-SNARE (TgStx19) instead of the canonical Use1, and its conditional ablation causes severe defects in the secretory system."},"narrative":{"mechanistic_narrative":"TgStx18 is an endoplasmic reticulum-resident SNARE protein in Toxoplasma gondii that functions in the secretory vesicular trafficking pathway [PMID:34340555]. Conditional ablation of TgStx18 causes severe defects in the secretory system, establishing its role in ER-associated vesicular trafficking [PMID:34340555]. Rather than pairing with the canonical Use1 Qc-SNARE found in other eukaryotes, TgStx18 partners with a novel ER-localized Qc-SNARE, TgStx19 [PMID:34340555]. Beyond these ER localization and partner findings, no further mechanistic detail (structural basis of the SNARE complex, direct binding kinetics, or the full set of trafficking cargo affected) has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Establishing where TgStx18 acts was the first step in placing it within the parasite's membrane trafficking machinery; localization to the ER positioned it as a candidate mediator of early secretory transport.","evidence":"Fluorescence localization analysis of SNARE proteins in Toxoplasma gondii","pmids":["34340555"],"confidence":"Medium","gaps":["Localization shown by imaging alone; no biochemical membrane fractionation","Does not define which sub-domain of the ER or trafficking step is served"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Whether TgStx18 is functionally required for secretion was unknown; conditional ablation demonstrated that loss disrupts the secretory system, establishing a causal role in ER-to-Golgi vesicular trafficking.","evidence":"Conditional knockout with phenotypic readout of secretory system integrity in Toxoplasma gondii","pmids":["34340555"],"confidence":"Medium","gaps":["Single lab, single phenotypic readout","Specific cargo or trafficking step whose failure drives the defect not identified","No rescue/complementation described"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"The SNARE partner of TgStx18 was unknown; identification of the novel ER-localized Qc-SNARE TgStx19 as its partner, in place of the canonical Use1, established a divergent SNARE complex architecture in this parasite.","evidence":"Localization analysis and partner identification via SNARE dissection assay in Toxoplasma gondii","pmids":["34340555"],"confidence":"Medium","gaps":["No direct binding assay described; partnership inferred from co-localization and ablation","Stoichiometry and full SNARE complex composition unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct biochemical basis of TgStx18–TgStx19 complex assembly and the molecular identity of the trafficking events it drives remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the SNARE complex","No direct in vitro binding or reconstitution","Full set of secretory cargo dependent on TgStx18 unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TgStx18–TgStx19 ER SNARE complex"],"partners":["TGSTX19 (NOVEL QC-SNARE)"],"other_free_text":["TgStx18 partners with the novel Qc-SNARE TgStx19 instead of the canonical Use1 found in other eukaryotes.","Conditional ablation of TgStx18 produces severe secretory system defects."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"34340555","id":"PMC_34340555","title":"The Dissection of SNAREs Reveals Key Factors for Vesicular Trafficking to the Endosome-like Compartment and Apicoplast via the Secretory System in Toxoplasma gondii.","date":"2021","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/34340555","citation_count":20,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3189,"output_tokens":683,"usd":0.009906,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5423,"output_tokens":1696,"usd":0.034757,"stage2_stop_reason":"end_turn"},"total_usd":0.044663,"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\": 2021,\n      \"finding\": \"TgStx18 localizes to the endoplasmic reticulum (ER) in Toxoplasma gondii, as determined by localization analysis of SNARE proteins.\",\n      \"method\": \"Fluorescence localization analysis (conditional ablation and imaging)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence (conditional ablation causing secretory system defects), single lab\",\n      \"pmids\": [\"34340555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Conditional ablation of TgStx18 (ER-residing SNARE) caused severe defects in the secretory system, establishing a functional role for TgStx18 in ER-to-Golgi vesicular trafficking.\",\n      \"method\": \"Conditional knockout with phenotypic readout of secretory system integrity\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockout with defined cellular phenotype, single lab, single primary method\",\n      \"pmids\": [\"34340555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TgStx19 (a novel Qc-SNARE) localizes to the ER and acts as a binding partner of TgStx18, replacing the canonical Use1 partner found in other eukaryotes.\",\n      \"method\": \"Localization analysis and partner identification by SNARE dissection assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-localization and functional partnership inferred from localization and conditional ablation, single lab, no direct binding assay described in abstract\",\n      \"pmids\": [\"34340555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgStx18 is an ER-resident SNARE in Toxoplasma gondii that functions in the secretory vesicular trafficking pathway, partnering with a novel Qc-SNARE (TgStx19) instead of the canonical Use1, and its conditional ablation causes severe defects in the secretory system.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgStx18 is an endoplasmic reticulum-resident SNARE protein in Toxoplasma gondii that functions in the secretory vesicular trafficking pathway [#0, #1]. Conditional ablation of TgStx18 causes severe defects in the secretory system, establishing its role in ER-associated vesicular trafficking [#1]. Rather than pairing with the canonical Use1 Qc-SNARE found in other eukaryotes, TgStx18 partners with a novel ER-localized Qc-SNARE, TgStx19 [#2]. Beyond these ER localization and partner findings, no further mechanistic detail (structural basis of the SNARE complex, direct binding kinetics, or the full set of trafficking cargo affected) has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing where TgStx18 acts was the first step in placing it within the parasite's membrane trafficking machinery; localization to the ER positioned it as a candidate mediator of early secretory transport.\",\n      \"evidence\": \"Fluorescence localization analysis of SNARE proteins in Toxoplasma gondii\",\n      \"pmids\": [\"34340555\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization shown by imaging alone; no biochemical membrane fractionation\",\n        \"Does not define which sub-domain of the ER or trafficking step is served\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether TgStx18 is functionally required for secretion was unknown; conditional ablation demonstrated that loss disrupts the secretory system, establishing a causal role in ER-to-Golgi vesicular trafficking.\",\n      \"evidence\": \"Conditional knockout with phenotypic readout of secretory system integrity in Toxoplasma gondii\",\n      \"pmids\": [\"34340555\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single phenotypic readout\",\n        \"Specific cargo or trafficking step whose failure drives the defect not identified\",\n        \"No rescue/complementation described\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The SNARE partner of TgStx18 was unknown; identification of the novel ER-localized Qc-SNARE TgStx19 as its partner, in place of the canonical Use1, established a divergent SNARE complex architecture in this parasite.\",\n      \"evidence\": \"Localization analysis and partner identification via SNARE dissection assay in Toxoplasma gondii\",\n      \"pmids\": [\"34340555\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct binding assay described; partnership inferred from co-localization and ablation\",\n        \"Stoichiometry and full SNARE complex composition unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical basis of TgStx18–TgStx19 complex assembly and the molecular identity of the trafficking events it drives remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the SNARE complex\",\n        \"No direct in vitro binding or reconstitution\",\n        \"Full set of secretory cargo dependent on TgStx18 unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005484\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006888\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"TgStx18–TgStx19 ER SNARE complex\"],\n    \"partners\": [\"TgStx19 (novel Qc-SNARE)\"],\n    \"other_free_text\": [\n      \"TgStx18 partners with the novel Qc-SNARE TgStx19 instead of the canonical Use1 found in other eukaryotes.\",\n      \"Conditional ablation of TgStx18 produces severe secretory system defects.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_267530","name":"STX18","product":"syntaxin-18","uniprot_acc":"S8G762","chromosome":"TGME49_chrIX","start_pos":598703},{"strain":"GT1","gene_id":"TGGT1_267530","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":432761},{"strain":"RH88","gene_id":"TGRH88_010590","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023090","start_pos":645422},{"strain":"VEG","gene_id":"TGVEG_267530","name":null,"product":"hypothetical protein","uniprot_acc":"V5BDB6","chromosome":"TGVEG_chrIX","start_pos":624650}]}