{"gene":"PF3D7_0904000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2005,"finding":"PFI0195c (PF3D7_0904000), a putative GTPase-activating protein (GAP), conferred mefloquine resistance (and also cycloheximide and halofantrine resistance) when expressed in Saccharomyces cerevisiae, and the encoded protein localized to the Golgi complex in yeast, consistent with potential GAP function.","method":"Yeast expression screen with P. falciparum library followed by mefloquine selection; immunolocalization in yeast; semi-quantitative RT-PCR in P. falciparum strains","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, heterologous yeast system; no direct biochemical demonstration of GAP activity; localization in yeast (not Plasmodium); functional consequence in yeast only","pmids":["15664648"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0904000 (PFI0195c) is a putative GTPase-activating protein that, when expressed heterologously in yeast, localizes to the Golgi and confers resistance to mefloquine, cycloheximide, and halofantrine, and is upregulated in some mefloquine-resistant P. falciparum strains, but its biochemical GAP activity and in-parasite mechanism remain uncharacterized."},"narrative":{"mechanistic_narrative":"PF3D7_0904000 (PFI0195c) is a putative GTPase-activating protein whose only functional characterization comes from heterologous expression in Saccharomyces cerevisiae, where it conferred resistance to mefloquine, cycloheximide, and halofantrine, localized to the Golgi complex, and was found upregulated in some P. falciparum strains by RT-PCR [PMID:15664648]. Beyond this single yeast-based study, its biochemical GAP activity, its endogenous localization and substrate in P. falciparum, and its in-parasite mechanism have not been characterized in the available corpus.","teleology":[{"year":2005,"claim":"To ask whether the uncharacterized PFI0195c contributes to antimalarial drug response, the gene was expressed heterologously and screened for a resistance phenotype, establishing the first functional link between this putative GAP and mefloquine resistance.","evidence":"Yeast expression of a P. falciparum library followed by mefloquine selection, with immunolocalization in yeast and semi-quantitative RT-PCR across P. falciparum strains","pmids":["15664648"],"confidence":"Low","gaps":["Single-lab heterologous yeast system; no direct biochemical demonstration of GAP activity","Golgi localization was shown in yeast, not in P. falciparum","No functional consequence demonstrated in the parasite itself; the specific GTPase substrate is unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0904000 possesses genuine GAP activity, what small GTPase it acts on, where it localizes in the parasite, and how it mechanistically influences mefloquine response in P. falciparum all remain unresolved.","evidence":"No direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No in vitro reconstitution of GAP activity","No identified GTPase target or interacting partners in the parasite","No endogenous localization or genetic knockout/knockdown phenotype in P. falciparum"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["GAP activity is inferred from sequence annotation only; no biochemical GAP assay has been performed for PF3D7_0904000.","Drug-resistance phenotype (mefloquine, cycloheximide, halofantrine) and Golgi localization were observed in heterologous S. cerevisiae, not in P. falciparum [#0].","PF3D7_0904000 was reported upregulated in some P. falciparum strains by semi-quantitative RT-PCR [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15664648","id":"PMC_15664648","title":"Identification of putative Plasmodium falciparum mefloquine resistance genes.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15664648","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PFI0195c"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3365,"output_tokens":431,"usd":0.00828,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4864,"output_tokens":1204,"usd":0.02721,"stage2_stop_reason":"end_turn"},"total_usd":0.03549,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"PFI0195c (PF3D7_0904000), a putative GTPase-activating protein (GAP), conferred mefloquine resistance (and also cycloheximide and halofantrine resistance) when expressed in Saccharomyces cerevisiae, and the encoded protein localized to the Golgi complex in yeast, consistent with potential GAP function.\",\n      \"method\": \"Yeast expression screen with P. falciparum library followed by mefloquine selection; immunolocalization in yeast; semi-quantitative RT-PCR in P. falciparum strains\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, heterologous yeast system; no direct biochemical demonstration of GAP activity; localization in yeast (not Plasmodium); functional consequence in yeast only\",\n      \"pmids\": [\"15664648\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0904000 (PFI0195c) is a putative GTPase-activating protein that, when expressed heterologously in yeast, localizes to the Golgi and confers resistance to mefloquine, cycloheximide, and halofantrine, and is upregulated in some mefloquine-resistant P. falciparum strains, but its biochemical GAP activity and in-parasite mechanism remain uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0904000 (PFI0195c) is a putative GTPase-activating protein whose only functional characterization comes from heterologous expression in Saccharomyces cerevisiae, where it conferred resistance to mefloquine, cycloheximide, and halofantrine, localized to the Golgi complex, and was found upregulated in some P. falciparum strains by RT-PCR [#0]. Beyond this single yeast-based study, its biochemical GAP activity, its endogenous localization and substrate in P. falciparum, and its in-parasite mechanism have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"To ask whether the uncharacterized PFI0195c contributes to antimalarial drug response, the gene was expressed heterologously and screened for a resistance phenotype, establishing the first functional link between this putative GAP and mefloquine resistance.\",\n      \"evidence\": \"Yeast expression of a P. falciparum library followed by mefloquine selection, with immunolocalization in yeast and semi-quantitative RT-PCR across P. falciparum strains\",\n      \"pmids\": [\"15664648\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single-lab heterologous yeast system; no direct biochemical demonstration of GAP activity\",\n        \"Golgi localization was shown in yeast, not in P. falciparum\",\n        \"No functional consequence demonstrated in the parasite itself; the specific GTPase substrate is unidentified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0904000 possesses genuine GAP activity, what small GTPase it acts on, where it localizes in the parasite, and how it mechanistically influences mefloquine response in P. falciparum all remain unresolved.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vitro reconstitution of GAP activity\",\n        \"No identified GTPase target or interacting partners in the parasite\",\n        \"No endogenous localization or genetic knockout/knockdown phenotype in P. falciparum\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046677\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"GAP activity is inferred from sequence annotation only; no biochemical GAP assay has been performed for PF3D7_0904000.\",\n      \"Drug-resistance phenotype (mefloquine, cycloheximide, halofantrine) and Golgi localization were observed in heterologous S. cerevisiae, not in P. falciparum [#0].\",\n      \"PF3D7_0904000 was reported upregulated in some P. falciparum strains by semi-quantitative RT-PCR [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0904000","name":null,"product":"GTPase-activating protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0417400","name":null,"product":"GTPase-activating protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0701700","name":null,"product":"GTPase-activating protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}