{"gene":"PF3D7_1417900","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2011,"finding":"Seven canonical ATP synthase subunits (including ATPTG9/PF3D7_1417900 as part of the complex) were epitope-tagged and expressed in transgenic P. falciparum lines; all but one localized to the mitochondrion. Blue native gel electrophoresis of mitochondrial membranes showed the ATP synthase complex has a molecular mass >1 million daltons, consistent with dimeric assembly, suggesting the presence of previously unknown subunits beyond the canonical ones.","method":"Epitope-tagging of subunits in transgenic lines, immunofluorescence localization, blue native gel electrophoresis of mitochondrial membranes","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by epitope-tagging and native PAGE in a single lab with two orthogonal methods; ATPTG9 is one of multiple subunits studied, limiting gene-specific resolution","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Computational/proteomics-based identification of ATP synthase subunit a (PF3D7_1417900/ATPTG9) as a candidate F(O) membrane anchor subunit in Plasmodium spp., noting that transmembrane helix IV of this subunit lacks an essential Arg residue found in canonical orthologs, suggesting a divergent mechanism.","method":"Bioinformatic structural fingerprint analysis combined with proteomics data from related protists","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of PF3D7_1417900 specifically","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Attempts to disrupt the genes encoding the β and γ subunits of P. falciparum ATP synthase were unsuccessful, suggesting the complex (of which ATPTG9/PF3D7_1417900 is a member) is essential for blood-stage parasite survival.","method":"Attempted gene disruption/knockout by transfection in P. falciparum blood stages","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — negative result from genetic disruption attempts in a single lab; essentiality inferred indirectly for the complex, not ATPTG9 specifically","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Knockout of the ATP synthase β subunit (a core component of the complex containing ATPTG9/PF3D7_1417900) in P. berghei only marginally reduced asexual blood-stage growth but completely blocked transmission through Anopheles stephensi mosquitoes; ookinetes lacking the β subunit were non-viable in the mosquito midgut and never formed oocysts or sporozoites. Genetic crossing with a male-deficient strain restored fertility, establishing that ATP synthase is essential for viability through the female, mitochondrion-carrying line of sexual reproduction.","method":"Gene knockout of β subunit in P. berghei, mouse-to-mouse transmission assays via A. stephensi, genetic complementation by crossing with male-deficient strain","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined phenotypic readout and genetic rescue, single lab; finding pertains to the ATP synthase complex broadly, not ATPTG9 specifically","pmids":["25831536"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1417900 (ATPTG9) is a subunit of the mitochondrial ATP synthase complex in Plasmodium falciparum; the complex localizes to the parasite mitochondrion, assembles as a large (>1 MDa) dimer, and appears essential for parasite viability — particularly during the mosquito phase of the life cycle — though no experiment has yet established a mechanistic function specific to ATPTG9 itself beyond its membership in this complex."},"narrative":{"mechanistic_narrative":"PF3D7_1417900 (ATPTG9) is a subunit of the >1 MDa dimeric mitochondrial ATP synthase complex of Plasmodium falciparum, identified as a complex member during epitope-tagging and blue native PAGE analysis of mitochondrial membranes, where all but one canonical subunit localized to the parasite mitochondrion [PMID:21984828]. Bioinformatic and proteomic analysis places ATPTG9 as a candidate F(O) membrane-anchor subunit a, but notes that its transmembrane helix IV lacks the essential Arg residue conserved in canonical orthologs, indicating a divergent architecture [PMID:19682605]. The ATP synthase complex is essential for parasite viability: gene disruption of its β and γ subunits failed in P. falciparum blood stages [PMID:21984828], and in P. berghei knockout of the β subunit only marginally impaired asexual growth yet completely blocked transmission through the female, mitochondrion-carrying sexual line in the mosquito [PMID:25831536]. No experiment in the available corpus has established a mechanistic function specific to ATPTG9 itself beyond its membership in this complex; all essentiality and localization data derive from other subunits, and the corpus establishes nothing about ATPTG9 individually beyond its being part of the ATP synthase complex.","teleology":[{"year":2009,"claim":"To assign ATPTG9 a role within the poorly annotated Plasmodium ATP synthase, computational analysis proposed it as the divergent F(O) membrane-anchor subunit a, framing the question of how the parasite complex differs mechanistically from canonical orthologs.","evidence":"Bioinformatic structural fingerprint analysis with proteomics data from related protists","pmids":["19682605"],"confidence":"Low","gaps":["Computational prediction only, with no direct experimental validation of PF3D7_1417900","The functional consequence of the missing essential Arg in transmembrane helix IV is untested","Subunit identity assignment not confirmed biochemically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"To determine where the ATP synthase resides and how it assembles, subunits including ATPTG9 were tagged and the native complex sized, establishing a mitochondrial, >1 MDa dimeric complex with likely non-canonical additional subunits.","evidence":"Epitope-tagging in transgenic P. falciparum, immunofluorescence localization, and blue native gel electrophoresis of mitochondrial membranes","pmids":["21984828"],"confidence":"Medium","gaps":["ATPTG9 was studied only as one of multiple subunits, so its own localization and topology are not individually resolved","The identity and stoichiometry of the inferred additional subunits are undefined","No direct evidence links ATPTG9 to a specific structural or catalytic role"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"To test whether the complex is dispensable, disruption of the β and γ subunits was attempted and failed, indicating the ATP synthase (of which ATPTG9 is a member) is essential in blood-stage parasites.","evidence":"Attempted gene disruption by transfection in P. falciparum blood stages","pmids":["21984828"],"confidence":"Medium","gaps":["Essentiality inferred indirectly from a negative knockout result, not for ATPTG9 specifically","Failure to disrupt does not distinguish catalytic from structural requirement","No conditional knockdown of ATPTG9 itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To resolve at which life-cycle stage the complex is required, β-subunit knockout in P. berghei showed the ATP synthase is largely dispensable for asexual growth but essential for transmission through the female sexual line, defining a mosquito-stage bottleneck.","evidence":"β-subunit knockout in P. berghei with mouse-to-mosquito transmission assays and genetic rescue by crossing with a male-deficient strain","pmids":["25831536"],"confidence":"Medium","gaps":["Phenotype pertains to the β subunit and the complex broadly, not ATPTG9 specifically","Does not establish whether ATPTG9 loss phenocopies β loss","Mechanistic basis of ookinete non-viability in the midgut is not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether ATPTG9 has any function distinct from its structural membership in the ATP synthase complex — including its subunit identity, membrane topology, and individual essentiality — remains unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No gene-specific knockout or knockdown of ATPTG9","No structural model confirming its assignment as subunit a","The functional impact of the divergent transmembrane helix IV is untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex (>1 MDa dimeric)"],"partners":["ATP SYNTHASE Β SUBUNIT","ATP SYNTHASE Γ SUBUNIT","CANONICAL ATP SYNTHASE SUBUNITS (AS COMPLEX MEMBERS)"],"other_free_text":["Predicted candidate F(O) membrane-anchor subunit a with a divergent transmembrane helix IV lacking the canonically essential Arg residue [#1].","ATP synthase complex is essential for P. falciparum blood-stage survival (inferred from failed β/γ disruption) [#2] and essential for transmission through the female sexual line in P. berghei [#3].","No mechanistic function specific to ATPTG9 beyond complex membership has been experimentally established in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25831536","id":"PMC_25831536","title":"Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase.","date":"2015","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25831536","citation_count":91,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25823686","id":"PMC_25823686","title":"Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25823686","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21984828","id":"PMC_21984828","title":"ATP synthase complex of Plasmodium falciparum: dimeric assembly in mitochondrial membranes and resistance to genetic disruption.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21984828","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2226706","id":"PMC_2226706","title":"Plasmodium falciparum: ATP/ADP transport across the parasitophorous vacuolar and plasma membranes.","date":"1990","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2226706","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19682605","id":"PMC_19682605","title":"Identification of mitochondrial Complex II subunits SDH3 and SDH4 and ATP synthase subunits a and b in Plasmodium spp.","date":"2009","source":"Mitochondrion","url":"https://pubmed.ncbi.nlm.nih.gov/19682605","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5004,"output_tokens":1262,"usd":0.016971,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6194,"output_tokens":2310,"usd":0.04436,"stage2_stop_reason":"end_turn"},"total_usd":0.061331,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Seven canonical ATP synthase subunits (including ATPTG9/PF3D7_1417900 as part of the complex) were epitope-tagged and expressed in transgenic P. falciparum lines; all but one localized to the mitochondrion. Blue native gel electrophoresis of mitochondrial membranes showed the ATP synthase complex has a molecular mass >1 million daltons, consistent with dimeric assembly, suggesting the presence of previously unknown subunits beyond the canonical ones.\",\n      \"method\": \"Epitope-tagging of subunits in transgenic lines, immunofluorescence localization, blue native gel electrophoresis of mitochondrial membranes\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by epitope-tagging and native PAGE in a single lab with two orthogonal methods; ATPTG9 is one of multiple subunits studied, limiting gene-specific resolution\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Computational/proteomics-based identification of ATP synthase subunit a (PF3D7_1417900/ATPTG9) as a candidate F(O) membrane anchor subunit in Plasmodium spp., noting that transmembrane helix IV of this subunit lacks an essential Arg residue found in canonical orthologs, suggesting a divergent mechanism.\",\n      \"method\": \"Bioinformatic structural fingerprint analysis combined with proteomics data from related protists\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of PF3D7_1417900 specifically\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Attempts to disrupt the genes encoding the β and γ subunits of P. falciparum ATP synthase were unsuccessful, suggesting the complex (of which ATPTG9/PF3D7_1417900 is a member) is essential for blood-stage parasite survival.\",\n      \"method\": \"Attempted gene disruption/knockout by transfection in P. falciparum blood stages\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — negative result from genetic disruption attempts in a single lab; essentiality inferred indirectly for the complex, not ATPTG9 specifically\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Knockout of the ATP synthase β subunit (a core component of the complex containing ATPTG9/PF3D7_1417900) in P. berghei only marginally reduced asexual blood-stage growth but completely blocked transmission through Anopheles stephensi mosquitoes; ookinetes lacking the β subunit were non-viable in the mosquito midgut and never formed oocysts or sporozoites. Genetic crossing with a male-deficient strain restored fertility, establishing that ATP synthase is essential for viability through the female, mitochondrion-carrying line of sexual reproduction.\",\n      \"method\": \"Gene knockout of β subunit in P. berghei, mouse-to-mouse transmission assays via A. stephensi, genetic complementation by crossing with male-deficient strain\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined phenotypic readout and genetic rescue, single lab; finding pertains to the ATP synthase complex broadly, not ATPTG9 specifically\",\n      \"pmids\": [\"25831536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1417900 (ATPTG9) is a subunit of the mitochondrial ATP synthase complex in Plasmodium falciparum; the complex localizes to the parasite mitochondrion, assembles as a large (>1 MDa) dimer, and appears essential for parasite viability — particularly during the mosquito phase of the life cycle — though no experiment has yet established a mechanistic function specific to ATPTG9 itself beyond its membership in this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1417900 (ATPTG9) is a subunit of the >1 MDa dimeric mitochondrial ATP synthase complex of Plasmodium falciparum, identified as a complex member during epitope-tagging and blue native PAGE analysis of mitochondrial membranes, where all but one canonical subunit localized to the parasite mitochondrion [#0]. Bioinformatic and proteomic analysis places ATPTG9 as a candidate F(O) membrane-anchor subunit a, but notes that its transmembrane helix IV lacks the essential Arg residue conserved in canonical orthologs, indicating a divergent architecture [#1]. The ATP synthase complex is essential for parasite viability: gene disruption of its β and γ subunits failed in P. falciparum blood stages [#2], and in P. berghei knockout of the β subunit only marginally impaired asexual growth yet completely blocked transmission through the female, mitochondrion-carrying sexual line in the mosquito [#3]. No experiment in the available corpus has established a mechanistic function specific to ATPTG9 itself beyond its membership in this complex; all essentiality and localization data derive from other subunits, and the corpus establishes nothing about ATPTG9 individually beyond its being part of the ATP synthase complex.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"To assign ATPTG9 a role within the poorly annotated Plasmodium ATP synthase, computational analysis proposed it as the divergent F(O) membrane-anchor subunit a, framing the question of how the parasite complex differs mechanistically from canonical orthologs.\",\n      \"evidence\": \"Bioinformatic structural fingerprint analysis with proteomics data from related protists\",\n      \"pmids\": [\"19682605\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational prediction only, with no direct experimental validation of PF3D7_1417900\", \"The functional consequence of the missing essential Arg in transmembrane helix IV is untested\", \"Subunit identity assignment not confirmed biochemically\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"To determine where the ATP synthase resides and how it assembles, subunits including ATPTG9 were tagged and the native complex sized, establishing a mitochondrial, >1 MDa dimeric complex with likely non-canonical additional subunits.\",\n      \"evidence\": \"Epitope-tagging in transgenic P. falciparum, immunofluorescence localization, and blue native gel electrophoresis of mitochondrial membranes\",\n      \"pmids\": [\"21984828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ATPTG9 was studied only as one of multiple subunits, so its own localization and topology are not individually resolved\", \"The identity and stoichiometry of the inferred additional subunits are undefined\", \"No direct evidence links ATPTG9 to a specific structural or catalytic role\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"To test whether the complex is dispensable, disruption of the β and γ subunits was attempted and failed, indicating the ATP synthase (of which ATPTG9 is a member) is essential in blood-stage parasites.\",\n      \"evidence\": \"Attempted gene disruption by transfection in P. falciparum blood stages\",\n      \"pmids\": [\"21984828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Essentiality inferred indirectly from a negative knockout result, not for ATPTG9 specifically\", \"Failure to disrupt does not distinguish catalytic from structural requirement\", \"No conditional knockdown of ATPTG9 itself\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To resolve at which life-cycle stage the complex is required, β-subunit knockout in P. berghei showed the ATP synthase is largely dispensable for asexual growth but essential for transmission through the female sexual line, defining a mosquito-stage bottleneck.\",\n      \"evidence\": \"β-subunit knockout in P. berghei with mouse-to-mosquito transmission assays and genetic rescue by crossing with a male-deficient strain\",\n      \"pmids\": [\"25831536\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phenotype pertains to the β subunit and the complex broadly, not ATPTG9 specifically\", \"Does not establish whether ATPTG9 loss phenocopies β loss\", \"Mechanistic basis of ookinete non-viability in the midgut is not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ATPTG9 has any function distinct from its structural membership in the ATP synthase complex — including its subunit identity, membrane topology, and individual essentiality — remains unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No gene-specific knockout or knockdown of ATPTG9\", \"No structural model confirming its assignment as subunit a\", \"The functional impact of the divergent transmembrane helix IV is untested\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0046933\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0015986\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\"Mitochondrial ATP synthase complex (>1 MDa dimeric)\"],\n    \"partners\": [\"ATP synthase β subunit\", \"ATP synthase γ subunit\", \"canonical ATP synthase subunits (as complex members)\"],\n    \"other_free_text\": [\n      \"Predicted candidate F(O) membrane-anchor subunit a with a divergent transmembrane helix IV lacking the canonically essential Arg residue [#1].\",\n      \"ATP synthase complex is essential for P. falciparum blood-stage survival (inferred from failed β/γ disruption) [#2] and essential for transmission through the female sexual line in P. berghei [#3].\",\n      \"No mechanistic function specific to ATPTG9 beyond complex membership has been experimentally established in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1417900","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1024800","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1340100","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATPTG9","evaluation":null}