{"gene":"TG_229170","gene_symbol":"FNT3","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2018,"finding":"FNT3 (TG_229170) is one of three FNT-type monocarboxylate/proton symporters localized to the plasma membrane of the T. gondii tachyzoite stage; it transports both l-lactate and formate in a pH-dependent manner.","method":"Heterologous expression/transport assay and subcellular localization (plasma membrane fractionation/imaging)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct transport assays with pH-dependence and subcellular localization established in a single lab study with multiple orthogonal methods (transport assay, localization, chemical biology)","pmids":["30237165"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"FNT3, along with the other two T. gondii FNTs, is inhibited by 2-hydroxy-chromanones; critical residues in the substrate-selectivity region of FNT3 determine differential specificity and sensitivity toward both substrates (l-lactate, formate) and these inhibitors, as identified by chemical biology and mutagenesis.","method":"Chemical biology approach with mutagenesis of substrate-selectivity residues; inhibitor sensitivity assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — active-site/selectivity-region mutagenesis combined with in vitro transport inhibition assays, single lab","pmids":["30237165"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"FNT3 is a plasma membrane-localized FNT-family monocarboxylate/proton symporter in T. gondii tachyzoites that transports l-lactate and formate in a pH-dependent manner, with substrate selectivity and inhibitor sensitivity governed by specific residues in its substrate-selectivity region, and is inhibitable by 2-hydroxy-chromanone compounds that block parasite growth."},"narrative":{"mechanistic_narrative":"FNT3 is a plasma membrane-localized formate/nitrite transporter (FNT)-family monocarboxylate/proton symporter of the Toxoplasma gondii tachyzoite that mediates pH-dependent transport of both l-lactate and formate [PMID:30237165]. Substrate selectivity and inhibitor sensitivity are governed by specific residues in its substrate-selectivity region, and FNT3 is blocked by 2-hydroxy-chromanone compounds [PMID:30237165]. Beyond these transport and inhibition properties, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing whether FNT3 is a functional transporter and where it acts defined its role as a plasma membrane symporter handling l-lactate and formate under pH control.","evidence":"Heterologous expression/transport assays with pH-dependence testing plus subcellular localization in T. gondii tachyzoites","pmids":["30237165"],"confidence":"Medium","gaps":["Directionality (efflux vs influx) and physiological substrate load in vivo not resolved","Contribution of FNT3 relative to the other two FNTs to parasite metabolism not dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Mapping which residues set substrate and inhibitor preference identified the substrate-selectivity region as the determinant of FNT3 specificity and revealed 2-hydroxy-chromanones as inhibitors.","evidence":"Chemical biology with mutagenesis of substrate-selectivity residues and inhibitor sensitivity assays","pmids":["30237165"],"confidence":"Medium","gaps":["No structural model of the substrate-selectivity region","Whether inhibition translates to selective anti-parasite efficacy in vivo not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Inhibited by 2-hydroxy-chromanone compounds; substrate-selectivity region residues govern specificity toward l-lactate and formate and inhibitor sensitivity [#1]","One of three plasma membrane FNT-type monocarboxylate/proton symporters in the T. gondii tachyzoite [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"30237165","id":"PMC_30237165","title":"The intracellular parasite Toxoplasma gondii harbors three druggable FNT-type formate and l-lactate transporters in the plasma membrane.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30237165","citation_count":29,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2912,"output_tokens":874,"usd":0.010923,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5694,"output_tokens":2053,"usd":0.039898,"stage2_stop_reason":"end_turn"},"total_usd":0.093934,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"re-read with subject anchor"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"FNT3 (TG_229170) is one of three FNT-type monocarboxylate/proton symporters localized to the plasma membrane of the T. gondii tachyzoite stage; it transports both l-lactate and formate in a pH-dependent manner.\",\n      \"method\": \"Heterologous expression/transport assay and subcellular localization (plasma membrane fractionation/imaging)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct transport assays with pH-dependence and subcellular localization established in a single lab study with multiple orthogonal methods (transport assay, localization, chemical biology)\",\n      \"pmids\": [\"30237165\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"FNT3, along with the other two T. gondii FNTs, is inhibited by 2-hydroxy-chromanones; critical residues in the substrate-selectivity region of FNT3 determine differential specificity and sensitivity toward both substrates (l-lactate, formate) and these inhibitors, as identified by chemical biology and mutagenesis.\",\n      \"method\": \"Chemical biology approach with mutagenesis of substrate-selectivity residues; inhibitor sensitivity assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site/selectivity-region mutagenesis combined with in vitro transport inhibition assays, single lab\",\n      \"pmids\": [\"30237165\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"FNT3 is a plasma membrane-localized FNT-family monocarboxylate/proton symporter in T. gondii tachyzoites that transports l-lactate and formate in a pH-dependent manner, with substrate selectivity and inhibitor sensitivity governed by specific residues in its substrate-selectivity region, and is inhibitable by 2-hydroxy-chromanone compounds that block parasite growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FNT3 is a plasma membrane-localized formate/nitrite transporter (FNT)-family monocarboxylate/proton symporter of the Toxoplasma gondii tachyzoite that mediates pH-dependent transport of both l-lactate and formate [#0]. Substrate selectivity and inhibitor sensitivity are governed by specific residues in its substrate-selectivity region, and FNT3 is blocked by 2-hydroxy-chromanone compounds [#1]. Beyond these transport and inhibition properties, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing whether FNT3 is a functional transporter and where it acts defined its role as a plasma membrane symporter handling l-lactate and formate under pH control.\",\n      \"evidence\": \"Heterologous expression/transport assays with pH-dependence testing plus subcellular localization in T. gondii tachyzoites\",\n      \"pmids\": [\n        \"30237165\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Directionality (efflux vs influx) and physiological substrate load in vivo not resolved\",\n        \"Contribution of FNT3 relative to the other two FNTs to parasite metabolism not dissected\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapping which residues set substrate and inhibitor preference identified the substrate-selectivity region as the determinant of FNT3 specificity and revealed 2-hydroxy-chromanones as inhibitors.\",\n      \"evidence\": \"Chemical biology with mutagenesis of substrate-selectivity residues and inhibitor sensitivity assays\",\n      \"pmids\": [\n        \"30237165\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the substrate-selectivity region\",\n        \"Whether inhibition translates to selective anti-parasite efficacy in vivo not established\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological role of FNT3-mediated lactate/formate flux in T. gondii metabolism and the structural basis of its transport cycle remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No high-resolution structure available\",\n        \"In vivo metabolic and virulence consequences of FNT3 loss not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0015129\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n      },\n      {\n        \"term_id\": \"GO:0015499\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n      },\n      {\n        \"term_id\": \"GO:0015355\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005886\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0015711\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Inhibited by 2-hydroxy-chromanone compounds; substrate-selectivity region residues govern specificity toward l-lactate and formate and inhibitor sensitivity [#1]\",\n      \"One of three plasma membrane FNT-type monocarboxylate/proton symporters in the T. gondii tachyzoite [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_229170","name":"FNT3","product":"formate/nitrite transporter FNT3","uniprot_acc":"S8GBB9","chromosome":"TGME49_chrVIII","start_pos":64909},{"strain":"GT1","gene_id":"TGGT1_229170","name":null,"product":"formate/nitrite transporter protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":65255},{"strain":"RH88","gene_id":"TGRH88_073900","name":null,"product":"formate/nitrite transporter protein","uniprot_acc":null,"chromosome":"CM023089","start_pos":5176671},{"strain":"VEG","gene_id":"TGVEG_229170","name":null,"product":"formate/nitrite transporter protein","uniprot_acc":"A0A125YY91","chromosome":"TGVEG_chrVIII","start_pos":70417}]}