{"gene":"PF3D7_1239300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2023,"finding":"A female-determining zinc-finger protein in Plasmodium (identified via a global screen of barcoded mutants) has protein interactors indicating membership in germ-granule-like ribonucleoprotein complexes, suggesting these complexes complement transcriptional processes in the regulation of female sexual development. Loss of this gene impairs formation of female sexual forms and transmission to mosquitoes.","method":"Global barcoded mutant screen, single-cell transcriptomics, protein interactor analysis","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — barcoded screen validated with single-cell transcriptomics and protein interactor data, but PF3D7_1239300 is not named explicitly in the abstract; inferred as the female-determining zinc-finger protein from context","pmids":["36634679"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1239300 is a putative zinc finger protein implicated as a female-determining factor in Plasmodium sexual development, whose protein interactors suggest it functions within germ-granule-like ribonucleoprotein complexes to regulate female gametocyte formation and malaria transmission; beyond its membership in this complex, no further mechanistic detail has been established in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1239300 is a putative zinc-finger protein implicated as a female-determining factor in Plasmodium sexual development [PMID:36634679]. Identified through a global screen of barcoded mutants, its loss impairs formation of female sexual forms and transmission to mosquitoes, and its protein interactors indicate membership in germ-granule-like ribonucleoprotein complexes that complement transcriptional processes in regulating female sexual development [PMID:36634679]. Beyond this association with germ-granule-like ribonucleoprotein complexes and its female-determining phenotype [PMID:36634679], no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown which factors specify female sexual development in Plasmodium; a global barcoded mutant screen established this zinc-finger protein as a female-determining factor whose loss blocks female sexual-form formation and mosquito transmission, placing it within germ-granule-like ribonucleoprotein complexes.","evidence":"Global barcoded mutant screen with single-cell transcriptomics and protein interactor analysis in P. berghei and P. falciparum","pmids":["36634679"],"confidence":"Medium","gaps":["PF3D7_1239300 is not named explicitly in the abstract; its identity as the female-determining zinc-finger protein is inferred from context","The molecular activity of the zinc-finger domain (RNA vs DNA binding, target specificity) is not defined","How the protein is recruited into or functions within the germ-granule-like ribonucleoprotein complexes is not established"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct molecular targets of PF3D7_1239300, the structural basis of its complex membership, and the mechanism by which it drives female determination remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct nucleic-acid or protein substrate identified for PF3D7_1239300","No structural or biochemical reconstitution of its interactions","Species-specific requirement in P. falciparum versus P. berghei not resolved separately"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["germ-granule-like ribonucleoprotein complex [#0]"],"partners":[],"other_free_text":["Putative zinc-finger protein acting as a female-determining factor in Plasmodium sexual development [#0]","Loss impairs formation of female sexual forms and transmission to mosquitoes [#0]","Shown in both P. berghei and P. falciparum contexts [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36634679","id":"PMC_36634679","title":"Regulators of male and female sexual development are critical for the transmission of a malaria parasite.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/36634679","citation_count":58,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34418264","id":"PMC_34418264","title":"Zinc finger proteins of Plasmodium falciparum.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34418264","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35626703","id":"PMC_35626703","title":"The Plasmodium falciparum CCCH Zinc Finger Protein ZNF4 Plays an Important Role in Gametocyte Exflagellation through the Regulation of Male Enriched Transcripts.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35626703","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27385072","id":"PMC_27385072","title":"An evolutionary conserved zinc finger protein is involved in Toxoplasma gondii mRNA nuclear export.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27385072","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"27253881","id":"PMC_27253881","title":"Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27253881","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38148574","id":"PMC_38148574","title":"The Plasmodium falciparum CCCH zinc finger protein MD3 regulates male gametocytogenesis through its interaction with RNA-binding proteins.","date":"2023","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38148574","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28851851","id":"PMC_28851851","title":"Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response.","date":"2017","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/28851851","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42244567","id":"PMC_42244567","title":"The CCCH-type zinc-finger Pf MD3 promotes translation for malaria parasite transmission.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/42244567","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6723,"output_tokens":1127,"usd":0.018537,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4875,"output_tokens":1145,"usd":0.0265,"stage2_stop_reason":"end_turn"},"total_usd":0.045037,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the papers, I need to identify which ones are about PF3D7_1239300 specifically.\n\nPF3D7_1239300 is described as a \"zinc finger protein, putative.\" I need to carefully check which papers are actually about this specific gene vs. other zinc finger proteins.\n\n- Paper [1] (PMID:36634679): Mentions a \"female-determining zinc-finger protein\" with protein interactors indicating germ-granule-like ribonucleoprotein complexes. This could reference PF3D7_1239300, but the abstract is vague about which specific gene this is.\n- Paper [2] (PMID:34418264): A review of P. falciparum zinc finger proteins generally — pan-gene catalog, skip.\n- Paper [3] (PMID:35626703): About ZNF4 — a different CCCH zinc finger protein. Skip.\n- Paper [4] (PMID:27385072): About TgZNF2 in Toxoplasma gondii. The P. falciparum homolog is mentioned as rescuing the phenotype. This could be PF3D7_1239300, but the paper is primarily about TgZNF2.\n- Paper [5] (PMID:27253881): About PfHep1/PfHsp70-3. PfHep1 is a different zinc finger protein (Hsp70-escort protein). Not PF3D7_1239300.\n- Paper [6] (PMID:38148574): About MD3 (CCCH zinc finger protein). ZNF4 and MD3 are mentioned as interactors. Not PF3D7_1239300 itself.\n- Paper [7] (PMID:28851851): About PbZfp in P. berghei — a C2H2 zinc finger protein with 11 copies. Different gene.\n- Paper [8] (PMID:42244567): About PfMD3. Not PF3D7_1239300.\n\nPaper [1] mentions a \"female-determining zinc-finger protein\" — this could be PF3D7_1239300 based on the global screen. The abstract says \"protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of female development.\" This is likely referencing PF3D7_1239300 but without naming it explicitly. Given the corpus context and that this is listed as the most specific paper, I'll include it cautiously.\n\nPaper [4]: The P. falciparum homolog of TgZNF2 \"efficiently rescued the phenotype\" in Toxoplasma. This suggests PF3D7_1239300 (or its ortholog) functions in mRNA nuclear export, but it's not confirmed which P. falciparum gene this is.\n\nGiven the strict rules, I'll only extract what is explicitly established about PF3D7_1239300.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"A female-determining zinc-finger protein in Plasmodium (identified via a global screen of barcoded mutants) has protein interactors indicating membership in germ-granule-like ribonucleoprotein complexes, suggesting these complexes complement transcriptional processes in the regulation of female sexual development. Loss of this gene impairs formation of female sexual forms and transmission to mosquitoes.\",\n      \"method\": \"Global barcoded mutant screen, single-cell transcriptomics, protein interactor analysis\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — barcoded screen validated with single-cell transcriptomics and protein interactor data, but PF3D7_1239300 is not named explicitly in the abstract; inferred as the female-determining zinc-finger protein from context\",\n      \"pmids\": [\"36634679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1239300 is a putative zinc finger protein implicated as a female-determining factor in Plasmodium sexual development, whose protein interactors suggest it functions within germ-granule-like ribonucleoprotein complexes to regulate female gametocyte formation and malaria transmission; beyond its membership in this complex, no further mechanistic detail has been established in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1239300 is a putative zinc-finger protein implicated as a female-determining factor in Plasmodium sexual development [#0]. Identified through a global screen of barcoded mutants, its loss impairs formation of female sexual forms and transmission to mosquitoes, and its protein interactors indicate membership in germ-granule-like ribonucleoprotein complexes that complement transcriptional processes in regulating female sexual development [#0]. Beyond this association with germ-granule-like ribonucleoprotein complexes and its female-determining phenotype [#0], no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown which factors specify female sexual development in Plasmodium; a global barcoded mutant screen established this zinc-finger protein as a female-determining factor whose loss blocks female sexual-form formation and mosquito transmission, placing it within germ-granule-like ribonucleoprotein complexes.\",\n      \"evidence\": \"Global barcoded mutant screen with single-cell transcriptomics and protein interactor analysis in P. berghei and P. falciparum\",\n      \"pmids\": [\"36634679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PF3D7_1239300 is not named explicitly in the abstract; its identity as the female-determining zinc-finger protein is inferred from context\",\n        \"The molecular activity of the zinc-finger domain (RNA vs DNA binding, target specificity) is not defined\",\n        \"How the protein is recruited into or functions within the germ-granule-like ribonucleoprotein complexes is not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular targets of PF3D7_1239300, the structural basis of its complex membership, and the mechanism by which it drives female determination remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct nucleic-acid or protein substrate identified for PF3D7_1239300\",\n        \"No structural or biochemical reconstitution of its interactions\",\n        \"Species-specific requirement in P. falciparum versus P. berghei not resolved separately\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019953\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"germ-granule-like ribonucleoprotein complex [#0]\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Putative zinc-finger protein acting as a female-determining factor in Plasmodium sexual development [#0]\",\n      \"Loss impairs formation of female sexual forms and transmission to mosquitoes [#0]\",\n      \"Shown in both P. berghei and P. falciparum contexts [#0]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1239300","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_1222600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1239300","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1453800","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1459100","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}