{"gene":"PF3D7_1440100","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2023,"finding":"The cohesin complex subunit SMC3 (a direct partner of RAD21 in the cohesin complex) was shown by ChIP-seq to occupy promoter regions of stage-specific genes during the intraerythrocytic developmental cycle of P. falciparum, where its enrichment inversely correlates with gene expression and chromatin accessibility; SMC3 knockdown upregulates a subset of genes involved in erythrocyte egress and invasion that are normally expressed at later stages, indicating that the cohesin complex contributes to transcriptional repression of stage-specific genes. RAD21 is identified as a core cohesin subunit present in P. falciparum, but the functional experiments in this paper were performed on SMC3, not directly on RAD21 (PF3D7_1440100).","method":"ChIP-seq, SMC3 knockdown (conditional knockdown during IDC), chromatin accessibility assay","journal":"EMBO reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RAD21 (PF3D7_1440100) is noted as a cohesin subunit present in P. falciparum but all functional experiments were performed on SMC3; no direct experiment was conducted on RAD21 itself in this paper.","pmids":["37592911"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"RAD21 (PF3D7_1440100) is established as a core subunit of the cohesin complex in Plasmodium falciparum, but no direct functional or mechanistic experiment has been performed on RAD21 itself in the available literature; the cohesin complex as a whole (characterized via its SMC3 subunit) contributes to transcriptional repression of stage-specific genes during the intraerythrocytic developmental cycle."},"narrative":{"mechanistic_narrative":"RAD21 (PF3D7_1440100) is identified as a core subunit of the cohesin complex in Plasmodium falciparum, together with its partner subunit SMC3 [PMID:37592911]. In the available corpus, all functional experiments were performed on the SMC3 subunit rather than on RAD21 itself: ChIP-seq showed SMC3 occupancy at promoters of stage-specific genes during the intraerythrocytic developmental cycle, where its enrichment inversely correlates with gene expression and chromatin accessibility, and SMC3 knockdown de-represses egress- and invasion-associated genes normally expressed at later stages, indicating that the cohesin complex contributes to transcriptional repression of stage-specific genes [PMID:37592911]. Beyond its membership in the cohesin complex, no direct functional or mechanistic experiment has been performed on RAD21 (PF3D7_1440100) in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown whether the P. falciparum cohesin complex regulates gene expression during the asexual cycle; this work established that cohesin (assayed via SMC3) represses stage-specific genes, and placed RAD21 within that complex as a core subunit.","evidence":"ChIP-seq and conditional SMC3 knockdown with chromatin accessibility assays during the intraerythrocytic developmental cycle","pmids":["37592911"],"confidence":"Low","gaps":["No experiment was performed directly on RAD21 (PF3D7_1440100); its individual contribution to the repressive function is not established.","The mechanism by which cohesin represses transcription (loop extrusion, promoter occlusion, or otherwise) is not resolved.","RAD21 localization, essentiality, and interaction interface within P. falciparum cohesin are uncharacterized."],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"What RAD21 (PF3D7_1440100) itself contributes to cohesin function in P. falciparum remains unknown, as no direct RAD21 perturbation, localization, or interaction experiment exists in the corpus.","evidence":"No direct experimental study of RAD21 in the available timeline","pmids":[],"confidence":"Low","gaps":["No RAD21-specific knockdown/knockout phenotype.","No direct evidence that RAD21 co-occupies the SMC3-bound promoters.","No structural or biochemical characterization of RAD21 within the P. falciparum cohesin complex."],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["cohesin complex"],"partners":["SMC3"],"other_free_text":["RAD21 (PF3D7_1440100) is annotated as a core cohesin subunit in P. falciparum, but all functional evidence in the corpus derives from experiments on the partner subunit SMC3, not on RAD21 itself [#0].","The cohesin complex (assayed via SMC3) occupies promoters of stage-specific genes and represses egress/invasion genes during the intraerythrocytic developmental cycle [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"37592911","id":"PMC_37592911","title":"Cohesin contributes to transcriptional repression of stage-specific genes in the human malaria parasite.","date":"2023","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/37592911","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37958695","id":"","title":"A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37958695","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD21"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25529755","id":"","title":"Sexual reproduction and genetic exchange in parasitic protists.","date":"2014","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/25529755","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD21"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18663385","id":"","title":"An expanded inventory of conserved meiotic genes provides evidence for sex in Trichomonas vaginalis.","date":"2007","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/18663385","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD21"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19440370","id":"","title":"Discovery of mating in the major African livestock pathogen Trypanosoma congolense.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19440370","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RAD21"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7238,"output_tokens":514,"usd":0.014712,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5054,"output_tokens":1269,"usd":0.028497,"stage2_stop_reason":"end_turn"},"total_usd":0.043209,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"The cohesin complex subunit SMC3 (a direct partner of RAD21 in the cohesin complex) was shown by ChIP-seq to occupy promoter regions of stage-specific genes during the intraerythrocytic developmental cycle of P. falciparum, where its enrichment inversely correlates with gene expression and chromatin accessibility; SMC3 knockdown upregulates a subset of genes involved in erythrocyte egress and invasion that are normally expressed at later stages, indicating that the cohesin complex contributes to transcriptional repression of stage-specific genes. RAD21 is identified as a core cohesin subunit present in P. falciparum, but the functional experiments in this paper were performed on SMC3, not directly on RAD21 (PF3D7_1440100).\",\n      \"method\": \"ChIP-seq, SMC3 knockdown (conditional knockdown during IDC), chromatin accessibility assay\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RAD21 (PF3D7_1440100) is noted as a cohesin subunit present in P. falciparum but all functional experiments were performed on SMC3; no direct experiment was conducted on RAD21 itself in this paper.\",\n      \"pmids\": [\"37592911\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"RAD21 (PF3D7_1440100) is established as a core subunit of the cohesin complex in Plasmodium falciparum, but no direct functional or mechanistic experiment has been performed on RAD21 itself in the available literature; the cohesin complex as a whole (characterized via its SMC3 subunit) contributes to transcriptional repression of stage-specific genes during the intraerythrocytic developmental cycle.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RAD21 (PF3D7_1440100) is identified as a core subunit of the cohesin complex in Plasmodium falciparum, together with its partner subunit SMC3 [#0]. In the available corpus, all functional experiments were performed on the SMC3 subunit rather than on RAD21 itself: ChIP-seq showed SMC3 occupancy at promoters of stage-specific genes during the intraerythrocytic developmental cycle, where its enrichment inversely correlates with gene expression and chromatin accessibility, and SMC3 knockdown de-represses egress- and invasion-associated genes normally expressed at later stages, indicating that the cohesin complex contributes to transcriptional repression of stage-specific genes [#0]. Beyond its membership in the cohesin complex, no direct functional or mechanistic experiment has been performed on RAD21 (PF3D7_1440100) in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown whether the P. falciparum cohesin complex regulates gene expression during the asexual cycle; this work established that cohesin (assayed via SMC3) represses stage-specific genes, and placed RAD21 within that complex as a core subunit.\",\n      \"evidence\": \"ChIP-seq and conditional SMC3 knockdown with chromatin accessibility assays during the intraerythrocytic developmental cycle\",\n      \"pmids\": [\"37592911\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiment was performed directly on RAD21 (PF3D7_1440100); its individual contribution to the repressive function is not established.\",\n        \"The mechanism by which cohesin represses transcription (loop extrusion, promoter occlusion, or otherwise) is not resolved.\",\n        \"RAD21 localization, essentiality, and interaction interface within P. falciparum cohesin are uncharacterized.\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"What RAD21 (PF3D7_1440100) itself contributes to cohesin function in P. falciparum remains unknown, as no direct RAD21 perturbation, localization, or interaction experiment exists in the corpus.\",\n      \"evidence\": \"No direct experimental study of RAD21 in the available timeline\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No RAD21-specific knockdown/knockout phenotype.\",\n        \"No direct evidence that RAD21 co-occupies the SMC3-bound promoters.\",\n        \"No structural or biochemical characterization of RAD21 within the P. falciparum cohesin complex.\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0045892\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"cohesin complex\"],\n    \"partners\": [\"SMC3\"],\n    \"other_free_text\": [\n      \"RAD21 (PF3D7_1440100) is annotated as a core cohesin subunit in P. falciparum, but all functional evidence in the corpus derives from experiments on the partner subunit SMC3, not on RAD21 itself [#0].\",\n      \"The cohesin complex (assayed via SMC3) occupies promoters of stage-specific genes and represses egress/invasion genes during the intraerythrocytic developmental cycle [#0].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1440100","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0414000). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1440100","name":null,"product":"cohesin complex subunit RAD21","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1304000","name":null,"product":"cohesin complex subunit, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1242200","name":null,"product":"cohesin complex subunit, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RAD21","evaluation":null}