{"gene":"PF3D7_1208800","run_date":"2026-09-11T10:06:41","timeline":{"discoveries":[{"year":2023,"finding":"PF3D7_1208800 (a zinc-finger protein) was identified as a female-determining factor in Plasmodium berghei sexual development; its protein interactors indicate it participates in germ-granule-like ribonucleoprotein complexes that regulate female gametocyte determination and differentiation.","method":"Global barcoded-mutant screen for sexual-stage essentiality combined with high-resolution single-cell transcriptomics of ten mutant parasites to map the regulatory cascade; protein interactors identified for the zinc-finger protein.","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen with single-cell transcriptomics and protein-interactor identification, single study but multiple orthogonal methods; complex membership established but mechanistic detail limited to abstract summary.","pmids":["36634679"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"finding":"The P. falciparum homolog of TgZNF2 (corresponding to PF3D7_1208800) can functionally complement loss of TgZNF2 in Toxoplasma gondii, rescuing the proliferation defect caused by TgZNF2 depletion, suggesting the mRNA nuclear export function of this zinc finger protein is conserved in P. falciparum.","method":"Heterologous complementation: expression of the P. falciparum homolog in an inducible TgZNF2 knockout T. gondii strain with ATc-mediated repression, followed by proliferation assay.","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single complementation experiment in a heterologous organism (T. gondii); no direct functional assay performed in P. falciparum itself.","pmids":["27385072"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1208800 is a zinc-finger protein that acts as a female-determining factor during Plasmodium sexual development, with its protein interactors indicating membership in germ-granule-like ribonucleoprotein complexes; a heterologous complementation experiment further suggests it conserves an mRNA nuclear export function."},"narrative":{"mechanistic_narrative":"PF3D7_1208800 is a zinc-finger protein that functions as a female-determining factor in Plasmodium berghei sexual development, where its identified protein interactors place it within germ-granule-like ribonucleoprotein complexes that regulate female gametocyte determination and differentiation [PMID:36634679]. Beyond its role in this regulatory cascade and its complex membership, no direct mechanistic assay has characterized its activity within P. falciparum itself; a heterologous complementation experiment in Toxoplasma gondii, in which the P. falciparum homolog rescued the proliferation defect of a TgZNF2 knockout, is the only evidence bearing on a possible conserved mRNA nuclear export function [PMID:27385072].","teleology":[{"year":2016,"claim":"To ask whether this zinc-finger protein retains an ancestral function, the P. falciparum homolog was tested for its ability to substitute for the Toxoplasma factor TgZNF2, establishing a candidate conserved mRNA nuclear export activity by cross-species rescue rather than by direct P. falciparum assay.","evidence":"heterologous complementation in an inducible TgZNF2-knockout T. gondii strain with ATc-mediated repression followed by a proliferation assay","pmids":["27385072"],"confidence":"Low","gaps":["no direct functional assay performed in P. falciparum itself; function inferred only from heterologous rescue","the molecular activity (mRNA nuclear export) was not demonstrated for the P. falciparum protein directly","does not address the protein's role in the native sexual-development context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"To define the protein's role in parasite biology, a genome-scale sexual-stage screen combined with single-cell transcriptomics and interactor mapping identified PF3D7_1208800 as a female-determining factor embedded in germ-granule-like ribonucleoprotein complexes, placing it in the regulatory cascade governing female gametocyte fate.","evidence":"global barcoded-mutant sexual-stage essentiality screen with single-cell transcriptomics of mutant parasites and protein-interactor identification","pmids":["36634679"],"confidence":"Medium","gaps":["mechanistic detail of how the zinc-finger protein enforces female determination is not resolved","the specific RNA targets or export cargo within the ribonucleoprotein complexes are not identified","whether the T. gondii-inferred export activity operates in this sexual-development context is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what direct molecular activity PF3D7_1208800 performs within its ribonucleoprotein complexes in P. falciparum, and how that activity mechanistically drives female gametocyte determination.","evidence":"no direct in-parasite biochemical or structural characterization present in the corpus","pmids":[],"confidence":"Low","gaps":["no RNA substrate or target identified in P. falciparum","no structural model or direct demonstration of nuclear export activity in the native parasite","the composition and function of the germ-granule-like complex beyond membership is uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["germ-granule-like ribonucleoprotein complex [#0]"],"partners":[],"other_free_text":["Identified as a female-determining factor in P. falciparum sexual development regulating female gametocyte determination and differentiation [#0].","The P. falciparum homolog functionally complements the T. gondii zinc-finger factor TgZNF2, rescuing a proliferation defect, consistent with a conserved mRNA nuclear export function [#1]."]}},"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":53,"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":"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4043,"output_tokens":675,"usd":0.011127,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5229,"output_tokens":1598,"usd":0.033048,"stage2_stop_reason":"end_turn"},"total_usd":0.044175,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard","patch_2026_09_11":["species attribution corrected after review"]},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"PF3D7_1208800 (a zinc-finger protein) was identified as a female-determining factor in Plasmodium sexual development; its protein interactors indicate it participates in germ-granule-like ribonucleoprotein complexes that regulate female gametocyte determination and differentiation.\",\n      \"method\": \"Global barcoded-mutant screen for sexual-stage essentiality combined with high-resolution single-cell transcriptomics of ten mutant parasites to map the regulatory cascade; protein interactors identified for the zinc-finger protein.\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen with single-cell transcriptomics and protein-interactor identification, single study but multiple orthogonal methods; complex membership established but mechanistic detail limited to abstract summary.\",\n      \"pmids\": [\"36634679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. falciparum homolog of TgZNF2 (corresponding to PF3D7_1208800) can functionally complement loss of TgZNF2 in Toxoplasma gondii, rescuing the proliferation defect caused by TgZNF2 depletion, suggesting the mRNA nuclear export function of this zinc finger protein is conserved in P. falciparum.\",\n      \"method\": \"Heterologous complementation: expression of the P. falciparum homolog in an inducible TgZNF2 knockout T. gondii strain with ATc-mediated repression, followed by proliferation assay.\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single complementation experiment in a heterologous organism (T. gondii); no direct functional assay performed in P. falciparum itself.\",\n      \"pmids\": [\"27385072\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1208800 is a zinc-finger protein that acts as a female-determining factor during Plasmodium sexual development, with its protein interactors indicating membership in germ-granule-like ribonucleoprotein complexes; a heterologous complementation experiment further suggests it conserves an mRNA nuclear export function.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1208800 is a zinc-finger protein that functions as a female-determining factor in Plasmodium falciparum sexual development, where its identified protein interactors place it within germ-granule-like ribonucleoprotein complexes that regulate female gametocyte determination and differentiation [#0]. Beyond its role in this regulatory cascade and its complex membership, no direct mechanistic assay has characterized its activity within P. falciparum itself; a heterologous complementation experiment in Toxoplasma gondii, in which the P. falciparum homolog rescued the proliferation defect of a TgZNF2 knockout, is the only evidence bearing on a possible conserved mRNA nuclear export function [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"To ask whether this zinc-finger protein retains an ancestral function, the P. falciparum homolog was tested for its ability to substitute for the Toxoplasma factor TgZNF2, establishing a candidate conserved mRNA nuclear export activity by cross-species rescue rather than by direct P. falciparum assay.\",\n      \"evidence\": \"heterologous complementation in an inducible TgZNF2-knockout T. gondii strain with ATc-mediated repression followed by a proliferation assay\",\n      \"pmids\": [\"27385072\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no direct functional assay performed in P. falciparum itself; function inferred only from heterologous rescue\",\n        \"the molecular activity (mRNA nuclear export) was not demonstrated for the P. falciparum protein directly\",\n        \"does not address the protein's role in the native sexual-development context\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To define the protein's role in parasite biology, a genome-scale sexual-stage screen combined with single-cell transcriptomics and interactor mapping identified PF3D7_1208800 as a female-determining factor embedded in germ-granule-like ribonucleoprotein complexes, placing it in the regulatory cascade governing female gametocyte fate.\",\n      \"evidence\": \"global barcoded-mutant sexual-stage essentiality screen with single-cell transcriptomics of mutant parasites and protein-interactor identification\",\n      \"pmids\": [\"36634679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"mechanistic detail of how the zinc-finger protein enforces female determination is not resolved\",\n        \"the specific RNA targets or export cargo within the ribonucleoprotein complexes are not identified\",\n        \"whether the T. gondii-inferred export activity operates in this sexual-development context is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what direct molecular activity PF3D7_1208800 performs within its ribonucleoprotein complexes in P. falciparum, and how that activity mechanistically drives female gametocyte determination.\",\n      \"evidence\": \"no direct in-parasite biochemical or structural characterization present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no RNA substrate or target identified in P. falciparum\",\n        \"no structural model or direct demonstration of nuclear export activity in the native parasite\",\n        \"the composition and function of the germ-granule-like complex beyond membership is uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003676\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006406\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019953\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"germ-granule-like ribonucleoprotein complex [#0]\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Identified as a female-determining factor in P. falciparum sexual development regulating female gametocyte determination and differentiation [#0].\",\n      \"The P. falciparum homolog functionally complements the T. gondii zinc-finger factor TgZNF2, rescuing a proliferation defect, consistent with a conserved mRNA nuclear export function [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1208800","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0607300","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1308700","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}