{"gene":"TG_212270","gene_symbol":"CLIP","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2023,"finding":"CLIP (CLAMP-linked invasion protein) forms a distinct microneme protein complex with CLAMP and SPATR in Toxoplasma gondii, and knockdown of CLIP disrupts rhoptry discharge following host-cell contact, establishing an essential role in invasion.","method":"Co-immunoprecipitation/complex identification, conditional knockdown with rhoptry discharge assay as phenotypic readout","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal complex identification combined with conditional knockdown and specific functional readout (rhoptry discharge), single lab but multiple orthogonal methods","pmids":["37886905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"CLIP is a microneme protein in Toxoplasma gondii that forms an essential trimeric complex with CLAMP and SPATR; knockdown of CLIP disrupts rhoptry discharge upon host-cell contact, thereby blocking invasion and preventing parasite-induced perforation of the host cell plasma membrane."},"narrative":{"mechanistic_narrative":"CLIP (CLAMP-linked invasion protein) is a microneme protein of Toxoplasma gondii that acts in the host-cell invasion machinery by forming a distinct trimeric complex with CLAMP and SPATR [PMID:37886905]. Conditional knockdown of CLIP disrupts rhoptry discharge following host-cell contact, establishing the complex as essential for invasion [PMID:37886905]. Beyond its role in linking complex integrity to rhoptry exocytosis, no additional biochemical or structural mechanism for CLIP has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Whether an uncharacterized microneme factor coordinated with rhoptry discharge existed was unknown; identifying CLIP as an obligate partner of CLAMP and SPATR whose loss blocks rhoptry discharge established a defined complex required for invasion.","evidence":"Reciprocal co-immunoprecipitation/complex identification with conditional knockdown scored by a rhoptry discharge assay in Toxoplasma gondii","pmids":["37886905"],"confidence":"High","gaps":["Stoichiometry, architecture, and direct binding interfaces of the CLIP-CLAMP-SPATR complex not resolved","Molecular step by which the complex triggers or licenses rhoptry discharge not defined","Individual contribution of CLIP versus CLAMP and SPATR not separately dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CLIP-CLAMP-SPATR microneme complex"],"partners":["CLAMP","SPATR"],"other_free_text":["Depletion of the CLIP/CLAMP complex abolishes parasite-induced perforation of the host cell plasma membrane during invasion [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"16889642","id":"PMC_16889642","title":"Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16889642","citation_count":67,"is_preprint":false},{"pmid":"37886905","id":"PMC_37886905","title":"A conserved complex of microneme proteins mediates rhoptry discharge in Toxoplasma.","date":"2023","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/37886905","citation_count":21,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3965,"output_tokens":559,"usd":0.01014,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5284,"output_tokens":1517,"usd":0.032172,"stage2_stop_reason":"end_turn"},"total_usd":0.044082,"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":"summary amended"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"CLIP (CLAMP-linked invasion protein) forms a distinct microneme protein complex with CLAMP and SPATR in Toxoplasma gondii, and knockdown of CLIP disrupts rhoptry discharge following host-cell contact, establishing an essential role in invasion.\",\n      \"method\": \"Co-immunoprecipitation/complex identification, conditional knockdown with rhoptry discharge assay as phenotypic readout\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal complex identification combined with conditional knockdown and specific functional readout (rhoptry discharge), single lab but multiple orthogonal methods\",\n      \"pmids\": [\"37886905\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Conditional depletion of CLIP (as part of the CLAMP complex) in Toxoplasma gondii abolishes parasite-induced perforation of the host cell plasma membrane during invasion, linking CLIP/CLAMP complex function to rhoptry exocytosis and host membrane disruption.\",\n      \"method\": \"Fluorescence imaging-based host cell perforation assay with conditional knockdown parasites\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — novel assay with clear phenotypic readout, but preprint, single lab, and CLIP is grouped with CLAMP rather than individually dissected\",\n      \"pmids\": [\"39605356\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CLIP is a microneme protein in Toxoplasma gondii that forms an essential trimeric complex with CLAMP and SPATR; knockdown of CLIP disrupts rhoptry discharge upon host-cell contact, thereby blocking invasion and preventing parasite-induced perforation of the host cell plasma membrane.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CLIP (CLAMP-linked invasion protein) is a microneme protein of Toxoplasma gondii that acts in the host-cell invasion machinery by forming a distinct trimeric complex with CLAMP and SPATR [#0]. Conditional knockdown of CLIP disrupts rhoptry discharge following host-cell contact, establishing the complex as essential for invasion [#0]. Beyond its role in linking complex integrity to rhoptry exocytosis, no additional biochemical or structural mechanism for CLIP has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether an uncharacterized microneme factor coordinated with rhoptry discharge existed was unknown; identifying CLIP as an obligate partner of CLAMP and SPATR whose loss blocks rhoptry discharge established a defined complex required for invasion.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation/complex identification with conditional knockdown scored by a rhoptry discharge assay in Toxoplasma gondii\",\n      \"pmids\": [\"37886905\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Stoichiometry, architecture, and direct binding interfaces of the CLIP-CLAMP-SPATR complex not resolved\",\n        \"Molecular step by which the complex triggers or licenses rhoptry discharge not defined\",\n        \"Individual contribution of CLIP versus CLAMP and SPATR not separately dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether the CLIP/CLAMP complex acts specifically at the level of host membrane breach was unknown; depleting the complex abolished parasite-induced perforation of the host plasma membrane, linking complex function to rhoptry exocytosis-driven membrane disruption.\",\n      \"evidence\": \"Fluorescence imaging-based host cell perforation assay with conditional knockdown parasites (preprint) in Toxoplasma gondii\",\n      \"pmids\": [\"39605356\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Preprint; CLIP is analyzed as part of the CLAMP complex rather than individually dissected\",\n        \"Whether perforation loss is a direct consequence of the CLIP complex or a downstream effect of failed rhoptry discharge is not separated\",\n        \"Molecular mechanism connecting the complex to membrane perforation not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of CLIP, its precise role within the trimeric complex, and the mechanism by which the complex controls rhoptry discharge and host membrane perforation remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No structural model of the CLIP-CLAMP-SPATR complex\",\n        \"No defined molecular activity for CLIP itself\",\n        \"Mechanism of coupling complex integrity to rhoptry exocytosis unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"microneme\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"host cell invasion / rhoptry discharge\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"CLIP-CLAMP-SPATR microneme complex\"],\n    \"partners\": [\"CLAMP\", \"SPATR\"],\n    \"other_free_text\": [\n      \"Depletion of the CLIP/CLAMP complex abolishes parasite-induced perforation of the host cell plasma membrane during invasion [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_212270","name":"CLIP","product":"CLAMP-linked invasion protein CLIP","uniprot_acc":"S8ETY6","chromosome":"TGME49_chrX","start_pos":3950165},{"strain":"GT1","gene_id":"TGGT1_212270","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":3855671},{"strain":"RH88","gene_id":"TGRH88_043030","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023091","start_pos":3598327},{"strain":"VEG","gene_id":"TGVEG_212270","name":null,"product":"hypothetical protein","uniprot_acc":"B9PWK3","chromosome":"TGVEG_chrX","start_pos":3860532}]}