{"gene":"TG_268830","gene_symbol":"ICAP18","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2018,"finding":"ICAP18 was identified as a previously unknown subunit of the Toxoplasma gondii mitochondrial ATP synthase complex, lacking homologs outside the Apicomplexa phylum. Structural modeling suggests ICAP18 is distantly related to mammalian stator subunits, and biochemical analysis confirmed it forms part of the ATP synthase complex.","method":"Sequence-based identification, structural modeling, and biochemical complex analysis (co-purification/complex membership assay)","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complex membership established biochemically and supported by structural modeling in a single study with multiple orthogonal approaches, but direct functional depletion of ICAP18 itself was not reported (only ICAP2 depletion was characterized)","pmids":["30204085"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"ICAP18 is discussed as a component of the Toxoplasma gondii ATP synthase involved in crista formation and maintenance, consistent with its role as a stator-related subunit of the inner mitochondrial membrane complex.","method":"Review synthesis of experimental findings from prior studies (no new experiments on ICAP18 directly)","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 4 / Weak — review paper citing prior work, no new direct experiment on ICAP18","pmids":["41789725"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ICAP18 is a novel, apicomplexan-specific subunit of the Toxoplasma gondii mitochondrial ATP synthase that is distantly related to mammalian stator subunits and forms part of the assembled ATP synthase complex, likely contributing to stator function in linking the catalytic and rotary portions of this essential metabolic machine."},"narrative":{"mechanistic_narrative":"ICAP18 is an apicomplexan-specific subunit of the Toxoplasma gondii mitochondrial ATP synthase complex, lacking homologs outside the Apicomplexa [PMID:30204085]. Structural modeling places it as a distant relative of mammalian stator subunits, and biochemical complex analysis confirmed that it co-purifies as an integral part of the assembled ATP synthase [PMID:30204085]. Beyond its identification and confirmed complex membership [PMID:30204085], no direct functional depletion of ICAP18 itself has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether the Toxoplasma ATP synthase contains lineage-specific subunits beyond the canonical conserved core was unknown; identifying ICAP18 as a genuine complex member established that the parasite ATP synthase is built partly from apicomplexan-specific components.","evidence":"Sequence-based identification, structural modeling, and biochemical complex membership assay in Toxoplasma gondii","pmids":["30204085"],"confidence":"Medium","gaps":["Direct functional depletion of ICAP18 itself was not performed (only ICAP2 depletion was characterized)","The predicted stator function is inferred from structural modeling, not from a functional assay","The precise position and interaction partners within the complex are not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"A review contextualized ICAP18 as a stator-related ATP synthase subunit linked to crista formation and maintenance, integrating it into the broader model of inner mitochondrial membrane organization.","evidence":"Review synthesis of prior experimental findings, no new experiments on ICAP18","pmids":["41789725"],"confidence":"Low","gaps":["No new direct experiment on ICAP18; the crista role is inferred from complex membership rather than tested for ICAP18 specifically","Causal contribution of ICAP18 to crista morphology not demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The functional consequence of ICAP18 loss and its specific mechanistic contribution to stator function and ATP synthase activity remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional knockdown or knockout of ICAP18 reported","No structural determination confirming the modeled stator position","No measurement of ATP synthase activity or crista morphology upon ICAP18 depletion"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex"],"partners":[],"other_free_text":["Apicomplexan-specific subunit lacking homologs outside the phylum [#0]","Structurally modeled as distantly related to mammalian stator subunits [#0]","Implicated in crista formation and maintenance via its ATP synthase membership [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"8579614","id":"PMC_8579614","title":"Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from potato tubers (Solanum tuberosum).","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8579614","citation_count":263,"is_preprint":false},{"pmid":"25879281","id":"PMC_25879281","title":"The NLRP1 inflammasomes.","date":"2015","source":"Immunological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/25879281","citation_count":200,"is_preprint":false},{"pmid":"8703025","id":"PMC_8703025","title":"Partial purification and immunohistochemical localization of ATP diphosphohydrolase from Schistosoma mansoni. Immunological cross-reactivities with potato apyrase and Toxoplasma gondii nucleoside triphosphate hydrolase.","date":"1996","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8703025","citation_count":121,"is_preprint":false},{"pmid":"30204085","id":"PMC_30204085","title":"Identification of cryptic subunits from an apicomplexan ATP synthase.","date":"2018","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/30204085","citation_count":53,"is_preprint":false},{"pmid":"30685461","id":"PMC_30685461","title":"Drug Resistance in Protozoan Parasites: An Incessant Wrestle for Survival.","date":"2019","source":"Journal of global antimicrobial resistance","url":"https://pubmed.ncbi.nlm.nih.gov/30685461","citation_count":37,"is_preprint":false},{"pmid":"41789725","id":"PMC_41789725","title":"Unconventional model organisms bend our view on mitochondrial cristae.","date":"2026","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/41789725","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5012,"output_tokens":576,"usd":0.011838,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5285,"output_tokens":1419,"usd":0.03095,"stage2_stop_reason":"end_turn"},"total_usd":0.042788,"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\": 2018,\n      \"finding\": \"ICAP18 was identified as a previously unknown subunit of the Toxoplasma gondii mitochondrial ATP synthase complex, lacking homologs outside the Apicomplexa phylum. Structural modeling suggests ICAP18 is distantly related to mammalian stator subunits, and biochemical analysis confirmed it forms part of the ATP synthase complex.\",\n      \"method\": \"Sequence-based identification, structural modeling, and biochemical complex analysis (co-purification/complex membership assay)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complex membership established biochemically and supported by structural modeling in a single study with multiple orthogonal approaches, but direct functional depletion of ICAP18 itself was not reported (only ICAP2 depletion was characterized)\",\n      \"pmids\": [\"30204085\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ICAP18 is discussed as a component of the Toxoplasma gondii ATP synthase involved in crista formation and maintenance, consistent with its role as a stator-related subunit of the inner mitochondrial membrane complex.\",\n      \"method\": \"Review synthesis of experimental findings from prior studies (no new experiments on ICAP18 directly)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — review paper citing prior work, no new direct experiment on ICAP18\",\n      \"pmids\": [\"41789725\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ICAP18 is a novel, apicomplexan-specific subunit of the Toxoplasma gondii mitochondrial ATP synthase that is distantly related to mammalian stator subunits and forms part of the assembled ATP synthase complex, likely contributing to stator function in linking the catalytic and rotary portions of this essential metabolic machine.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ICAP18 is an apicomplexan-specific subunit of the Toxoplasma gondii mitochondrial ATP synthase complex, lacking homologs outside the Apicomplexa [#0]. Structural modeling places it as a distant relative of mammalian stator subunits, and biochemical complex analysis confirmed that it co-purifies as an integral part of the assembled ATP synthase [#0]. Beyond its identification and confirmed complex membership [#0], no direct functional depletion of ICAP18 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the Toxoplasma ATP synthase contains lineage-specific subunits beyond the canonical conserved core was unknown; identifying ICAP18 as a genuine complex member established that the parasite ATP synthase is built partly from apicomplexan-specific components.\",\n      \"evidence\": \"Sequence-based identification, structural modeling, and biochemical complex membership assay in Toxoplasma gondii\",\n      \"pmids\": [\"30204085\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct functional depletion of ICAP18 itself was not performed (only ICAP2 depletion was characterized)\",\n        \"The predicted stator function is inferred from structural modeling, not from a functional assay\",\n        \"The precise position and interaction partners within the complex are not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"A review contextualized ICAP18 as a stator-related ATP synthase subunit linked to crista formation and maintenance, integrating it into the broader model of inner mitochondrial membrane organization.\",\n      \"evidence\": \"Review synthesis of prior experimental findings, no new experiments on ICAP18\",\n      \"pmids\": [\"41789725\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No new direct experiment on ICAP18; the crista role is inferred from complex membership rather than tested for ICAP18 specifically\",\n        \"Causal contribution of ICAP18 to crista morphology not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The functional consequence of ICAP18 loss and its specific mechanistic contribution to stator function and ATP synthase activity remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No conditional knockdown or knockout of ICAP18 reported\",\n        \"No structural determination confirming the modeled stator position\",\n        \"No measurement of ATP synthase activity or crista morphology upon ICAP18 depletion\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0046933\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0015986\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Mitochondrial ATP synthase complex\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Apicomplexan-specific subunit lacking homologs outside the phylum [#0]\",\n      \"Structurally modeled as distantly related to mammalian stator subunits [#0]\",\n      \"Implicated in crista formation and maintenance via its ATP synthase membership [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_268830","name":"ICAP18","product":"ATP synthase subunit delta","uniprot_acc":"S8F0X4","chromosome":"TGME49_chrVIII","start_pos":6261327},{"strain":"ME49","gene_id":"TGME49_268835","name":null,"product":"hypothetical protein","uniprot_acc":"S8F489","chromosome":"TGME49_chrVIII","start_pos":6259358},{"strain":"GT1","gene_id":"TGGT1_268835","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":6256688},{"strain":"RH88","gene_id":"TGRH88_082420","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":11377130},{"strain":"RH88","gene_id":"TGRH88_082430","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":11378879},{"strain":"VEG","gene_id":"TGVEG_268835","name":null,"product":"hypothetical protein","uniprot_acc":"V4ZS66","chromosome":"TGVEG_chrVIII","start_pos":6274482}]}