{"gene":"TG_300240","gene_symbol":"STX6","run_date":"2026-09-08T15:15:12","timeline":{"discoveries":[{"year":2013,"finding":"TgStx6 (Toxoplasma gondii Syntaxin 6) localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN), and overexpression causes expanded ELCs, a fragmented Golgi, and defects in inner membrane complex (IMC) maturation, establishing a role in retrograde vesicular transport between ELCs, the TGN, and the Golgi complex.","method":"Overexpression of TgStx6 followed by fluorescence microscopy to assess organelle morphology (ELC expansion, Golgi fragmentation, IMC maturation defects) and localization studies","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with functional consequence via overexpression phenotype, single lab, two orthogonal readouts (organelle morphology + IMC maturation defect)","pmids":["23962112"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"finding":"Overexpression of TgStx6 does not affect micronemes, rhoptries, or the apicoplast, indicating that TgStx6-dependent retrograde transport through the TGN is distinct from the pathways delivering proteins to these apical organelles.","method":"Fluorescence microscopy of organelle markers following TgStx6 overexpression","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct organelle marker analysis in overexpression, single lab; negative finding (no effect on micronemes/rhoptries/apicoplast) is itself mechanistically informative for pathway specificity","pmids":["23962112"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgStx6 (Stx6) acts in a coordinated manner with TgVps45 and Stx16 in the biogenesis of the inner membrane complex (alveoli) in both Toxoplasma gondii and Plasmodium falciparum, placing it in the endolysosomal/TGN vesicular trafficking pathway upstream of IMC formation.","method":"Functional genetic analysis of SNARE proteins and SEC1/Munc18 factors (TgVps45, Stx16, Stx6) with IMC biogenesis as phenotypic readout, assessed in both T. gondii and P. falciparum","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis across two organisms with defined cellular phenotype, single study but comparative validation adds weight","pmids":["33082261"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"TgStx6 is a SNARE protein that localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN) in Toxoplasma gondii, where it mediates retrograde vesicular transport between ELCs and the Golgi and, in coordination with TgVps45 and Stx16, contributes to inner membrane complex biogenesis, while being dispensable for trafficking to micronemes, rhoptries, and the apicoplast."},"narrative":{"mechanistic_narrative":"STX6 (Syntaxin 6) is a SNARE protein that mediates retrograde vesicular transport within the endosomal-to-Golgi axis of apicomplexan parasites [PMID:23962112]. In Toxoplasma gondii, TgStx6 localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN), and its overexpression expands ELCs, fragments the Golgi, and impairs inner membrane complex (IMC) maturation, defining its role in retrograde traffic between ELCs, the TGN, and the Golgi [PMID:23962112]. This TGN-associated retrograde pathway is functionally distinct from the routes delivering proteins to micronemes, rhoptries, and the apicoplast, which are unaffected by TgStx6 overexpression [PMID:23962112]. TgStx6 acts together with the SEC1/Munc18 factor TgVps45 and the syntaxin Stx16 during IMC (alveolar) biogenesis, a coordination conserved in both T. gondii and Plasmodium falciparum, placing STX6 in the endolysosomal/TGN trafficking pathway upstream of IMC formation [PMID:33082261]. Beyond these findings, no further mechanistic detail on STX6 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"It was unknown where TgStx6 acts in the parasite secretory system; localizing it to ELCs and the TGN and showing that its overexpression disrupts organelle morphology established its role in retrograde transport between ELCs, the TGN, and the Golgi.","evidence":"Overexpression of TgStx6 with fluorescence microscopy of organelle morphology and IMC maturation in T. gondii","pmids":["23962112"],"confidence":"Medium","gaps":["Phenotypes derive from overexpression rather than loss-of-function","Direct SNARE partners and cognate vesicle cargo not identified","Molecular basis of the IMC maturation defect not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2013,"claim":"Whether TgStx6 served general secretion or a specific pathway was unclear; showing that micronemes, rhoptries, and the apicoplast are unaffected established that the TgStx6-dependent retrograde route is distinct from apical organelle delivery pathways.","evidence":"Fluorescence microscopy of organelle markers following TgStx6 overexpression in T. gondii","pmids":["23962112"],"confidence":"Medium","gaps":["Negative result from overexpression; a knockout might reveal contributions to these pathways","Does not define which cargos depend on TgStx6"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"The trafficking machinery driving IMC biogenesis was undefined; genetic analysis showed TgStx6 acts with TgVps45 and Stx16 in alveolar/IMC formation in both T. gondii and P. falciparum, placing it in the endolysosomal/TGN pathway upstream of IMC assembly.","evidence":"Functional genetic analysis of SNARE/SEC1-Munc18 factors with IMC biogenesis readout in T. gondii and P. falciparum","pmids":["33082261"],"confidence":"Medium","gaps":["Direct physical interaction among Stx6, Vps45, and Stx16 not demonstrated","Vesicle identity and cargo carried to the nascent IMC unresolved","Single study"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The cognate SNARE complex partners, vesicle cargo, and the mechanistic link between retrograde ELC/TGN transport and IMC membrane assembly remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical identification of the STX6-containing SNARE complex","Cargo delivered via the TgStx6 retrograde pathway unknown","No structural model of STX6 function"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGVPS45","STX16"],"other_free_text":["Functions in inner membrane complex (alveoli) biogenesis in apicomplexan parasites [#2]","Dispensable for trafficking to micronemes, rhoptries, and the apicoplast [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23962112","id":"PMC_23962112","title":"Toxoplasma gondii Syntaxin 6 is required for vesicular transport between endosomal-like compartments and the Golgi complex.","date":"2013","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/23962112","citation_count":33,"is_preprint":false},{"pmid":"33082261","id":"PMC_33082261","title":"The ZIP Code of Vesicle Trafficking in Apicomplexa: SEC1/Munc18 and SNARE Proteins.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/33082261","citation_count":32,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3580,"output_tokens":991,"usd":0.012802,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5841,"output_tokens":2128,"usd":0.041203,"stage2_stop_reason":"end_turn"},"total_usd":0.054005,"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\": 2013,\n      \"finding\": \"TgStx6 (Toxoplasma gondii Syntaxin 6) localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN), and overexpression causes expanded ELCs, a fragmented Golgi, and defects in inner membrane complex (IMC) maturation, establishing a role in retrograde vesicular transport between ELCs, the TGN, and the Golgi complex.\",\n      \"method\": \"Overexpression of TgStx6 followed by fluorescence microscopy to assess organelle morphology (ELC expansion, Golgi fragmentation, IMC maturation defects) and localization studies\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with functional consequence via overexpression phenotype, single lab, two orthogonal readouts (organelle morphology + IMC maturation defect)\",\n      \"pmids\": [\"23962112\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Overexpression of TgStx6 does not affect micronemes, rhoptries, or the apicoplast, indicating that TgStx6-dependent retrograde transport through the TGN is distinct from the pathways delivering proteins to these apical organelles.\",\n      \"method\": \"Fluorescence microscopy of organelle markers following TgStx6 overexpression\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct organelle marker analysis in overexpression, single lab; negative finding (no effect on micronemes/rhoptries/apicoplast) is itself mechanistically informative for pathway specificity\",\n      \"pmids\": [\"23962112\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgStx6 (Stx6) acts in a coordinated manner with TgVps45 and Stx16 in the biogenesis of the inner membrane complex (alveoli) in both Toxoplasma gondii and Plasmodium falciparum, placing it in the endolysosomal/TGN vesicular trafficking pathway upstream of IMC formation.\",\n      \"method\": \"Functional genetic analysis of SNARE proteins and SEC1/Munc18 factors (TgVps45, Stx16, Stx6) with IMC biogenesis as phenotypic readout, assessed in both T. gondii and P. falciparum\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis across two organisms with defined cellular phenotype, single study but comparative validation adds weight\",\n      \"pmids\": [\"33082261\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgStx6 is a SNARE protein that localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN) in Toxoplasma gondii, where it mediates retrograde vesicular transport between ELCs and the Golgi and, in coordination with TgVps45 and Stx16, contributes to inner membrane complex biogenesis, while being dispensable for trafficking to micronemes, rhoptries, and the apicoplast.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"STX6 (Syntaxin 6) is a SNARE protein that mediates retrograde vesicular transport within the endosomal-to-Golgi axis of apicomplexan parasites [#0]. In Toxoplasma gondii, TgStx6 localizes to endosomal-like compartments (ELCs) and the trans-Golgi network (TGN), and its overexpression expands ELCs, fragments the Golgi, and impairs inner membrane complex (IMC) maturation, defining its role in retrograde traffic between ELCs, the TGN, and the Golgi [#0]. This TGN-associated retrograde pathway is functionally distinct from the routes delivering proteins to micronemes, rhoptries, and the apicoplast, which are unaffected by TgStx6 overexpression [#1]. TgStx6 acts together with the SEC1/Munc18 factor TgVps45 and the syntaxin Stx16 during IMC (alveolar) biogenesis, a coordination conserved in both T. gondii and Plasmodium falciparum, placing STX6 in the endolysosomal/TGN trafficking pathway upstream of IMC formation [#2]. Beyond these findings, no further mechanistic detail on STX6 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"It was unknown where TgStx6 acts in the parasite secretory system; localizing it to ELCs and the TGN and showing that its overexpression disrupts organelle morphology established its role in retrograde transport between ELCs, the TGN, and the Golgi.\",\n      \"evidence\": \"Overexpression of TgStx6 with fluorescence microscopy of organelle morphology and IMC maturation in T. gondii\",\n      \"pmids\": [\"23962112\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phenotypes derive from overexpression rather than loss-of-function\", \"Direct SNARE partners and cognate vesicle cargo not identified\", \"Molecular basis of the IMC maturation defect not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether TgStx6 served general secretion or a specific pathway was unclear; showing that micronemes, rhoptries, and the apicoplast are unaffected established that the TgStx6-dependent retrograde route is distinct from apical organelle delivery pathways.\",\n      \"evidence\": \"Fluorescence microscopy of organelle markers following TgStx6 overexpression in T. gondii\",\n      \"pmids\": [\"23962112\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative result from overexpression; a knockout might reveal contributions to these pathways\", \"Does not define which cargos depend on TgStx6\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The trafficking machinery driving IMC biogenesis was undefined; genetic analysis showed TgStx6 acts with TgVps45 and Stx16 in alveolar/IMC formation in both T. gondii and P. falciparum, placing it in the endolysosomal/TGN pathway upstream of IMC assembly.\",\n      \"evidence\": \"Functional genetic analysis of SNARE/SEC1-Munc18 factors with IMC biogenesis readout in T. gondii and P. falciparum\",\n      \"pmids\": [\"33082261\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical interaction among Stx6, Vps45, and Stx16 not demonstrated\", \"Vesicle identity and cargo carried to the nascent IMC unresolved\", \"Single study\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cognate SNARE complex partners, vesicle cargo, and the mechanistic link between retrograde ELC/TGN transport and IMC membrane assembly remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical identification of the STX6-containing SNARE complex\", \"Cargo delivered via the TgStx6 retrograde pathway unknown\", \"No structural model of STX6 function\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005484\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005802\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042147\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgVps45\", \"Stx16\"],\n    \"other_free_text\": [\n      \"Functions in inner membrane complex (alveoli) biogenesis in apicomplexan parasites [#2]\",\n      \"Dispensable for trafficking to micronemes, rhoptries, and the apicoplast [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_300240","name":"STX6","product":"syntaxin 6","uniprot_acc":"S8G1K9","chromosome":"TGME49_chrXII","start_pos":136943},{"strain":"GT1","gene_id":"TGGT1_300240","name":null,"product":"putative syntaxin 6 protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":99372},{"strain":"RH88","gene_id":"TGRH88_057140","name":null,"product":"putative syntaxin 6","uniprot_acc":null,"chromosome":"CM023093","start_pos":128746},{"strain":"VEG","gene_id":"TGVEG_300240","name":null,"product":"syntaxin 6, n-terminal protein","uniprot_acc":"B9Q2S3","chromosome":"TGVEG_chrXII","start_pos":129071}]}