{"gene":"TG_311310","gene_symbol":"CNA","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2015,"finding":"Calcineurin (a calcium-regulated phosphatase complex that includes CNA) critically regulates and stabilizes attachment of extracellular Toxoplasma gondii to host cells before intracellular entry, as determined by reverse-genetic and chemical-genetic approaches; calcineurin function is required for host cell engagement by T. gondii.","method":"Reverse-genetic and chemical-genetic approaches (loss-of-function with host cell attachment/invasion phenotype readout)","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reverse-genetic and chemical-genetic approaches in two apicomplexan systems with defined cellular phenotype, single study","pmids":["26118996"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"CNA (calcineurin catalytic subunit) in Toxoplasma gondii functions as part of a calcium-regulated phosphatase complex that critically regulates host cell recognition and stabilizes parasite attachment to host cells prior to intracellular entry, representing an ancestral mechanism for apicomplexan parasitism."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, CNA is the catalytic subunit of calcineurin, a calcium-regulated phosphatase complex that critically regulates recognition of and stable attachment to host cells by extracellular parasites prior to intracellular entry, such that calcineurin function is required for host cell engagement [PMID:26118996]. Beyond this role in host cell attachment established by loss-of-function studies, no further mechanistic detail about CNA has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"It was unknown how apicomplexan parasites stabilize their initial engagement with host cells; loss-of-function of the calcineurin complex established that this calcium-regulated phosphatase is required to stabilize extracellular parasite attachment before invasion.","evidence":"Reverse-genetic and chemical-genetic loss-of-function with host cell attachment/invasion phenotype readout in T. gondii and P. falciparum","pmids":["26118996"],"confidence":"Medium","gaps":["No substrates of the CNA phosphatase identified","The specific contribution of the CNA catalytic subunit versus the whole calcineurin complex is not resolved","Mechanism linking calcium signaling to attachment stabilization is not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Calcineurin (calcium-regulated phosphatase complex)"],"partners":[],"other_free_text":["Calcineurin function is required for stable attachment of extracellular T. gondii to host cells prior to invasion [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"26118996","id":"PMC_26118996","title":"Parasite Calcineurin Regulates Host Cell Recognition and Attachment by Apicomplexans.","date":"2015","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/26118996","citation_count":72,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2830,"output_tokens":566,"usd":0.00849,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5303,"output_tokens":1578,"usd":0.032982,"stage2_stop_reason":"end_turn"},"total_usd":0.075877,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","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\": 2015,\n      \"finding\": \"Calcineurin (a calcium-regulated phosphatase complex that includes CNA) critically regulates and stabilizes attachment of extracellular Toxoplasma gondii to host cells before intracellular entry, as determined by reverse-genetic and chemical-genetic approaches; calcineurin function is required for host cell engagement by T. gondii.\",\n      \"method\": \"Reverse-genetic and chemical-genetic approaches (loss-of-function with host cell attachment/invasion phenotype readout)\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reverse-genetic and chemical-genetic approaches in two apicomplexan systems with defined cellular phenotype, single study\",\n      \"pmids\": [\"26118996\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CNA (calcineurin catalytic subunit) in Toxoplasma gondii functions as part of a calcium-regulated phosphatase complex that critically regulates host cell recognition and stabilizes parasite attachment to host cells prior to intracellular entry, representing an ancestral mechanism for apicomplexan parasitism.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, CNA is the catalytic subunit of calcineurin, a calcium-regulated phosphatase complex that critically regulates recognition of and stable attachment to host cells by extracellular parasites prior to intracellular entry, such that calcineurin function is required for host cell engagement [#0]. Beyond this role in host cell attachment established by loss-of-function studies, no further mechanistic detail about CNA has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"It was unknown how apicomplexan parasites stabilize their initial engagement with host cells; loss-of-function of the calcineurin complex established that this calcium-regulated phosphatase is required to stabilize extracellular parasite attachment before invasion.\",\n      \"evidence\": \"Reverse-genetic and chemical-genetic loss-of-function with host cell attachment/invasion phenotype readout in T. gondii and P. falciparum\",\n      \"pmids\": [\"26118996\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No substrates of the CNA phosphatase identified\",\n        \"The specific contribution of the CNA catalytic subunit versus the whole calcineurin complex is not resolved\",\n        \"Mechanism linking calcium signaling to attachment stabilization is not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular substrates of CNA, its regulatory partners, and the biochemical mechanism by which calcineurin activity stabilizes host cell attachment remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct dephosphorylation substrate identified\",\n        \"No structural or biochemical characterization of the CNA subunit\",\n        \"Regulatory calcium-sensing input not mapped\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004722\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}, {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Calcineurin (calcium-regulated phosphatase complex)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Calcineurin function is required for stable attachment of extracellular T. gondii to host cells prior to invasion [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_311310","name":"CNA","product":"serine/threonine protein phosphatase 2B catalytic subunit A","uniprot_acc":"A0A125YWN8","chromosome":"TGME49_chrXI","start_pos":1960208},{"strain":"GT1","gene_id":"TGGT1_311310","name":null,"product":"protein phosphatase 2B catalytic subunit, calcineurin family phosphatse superfamily protein","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":1924815},{"strain":"RH88","gene_id":"TGRH88_050780","name":null,"product":"protein phosphatase 2B catalytic subunit, calcineurin family phosphatse superfamily protein","uniprot_acc":null,"chromosome":"CM023092","start_pos":2010466},{"strain":"VEG","gene_id":"TGVEG_311310","name":null,"product":"protein phosphatase 2B catalytic subunit, calcineurin family phosphatse superfamily protein","uniprot_acc":"V4ZIA1","chromosome":"TGVEG_chrXI","start_pos":1973684}]}