{"gene":"PF3D7_0927200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2023,"finding":"GD1 (PF3D7_0927200) was identified as a protein interactor of the CCCH zinc finger protein MD3 in P. falciparum gametocytes, as part of a regulatory complex involved in post-transcriptional fine-tuning of male gametocytogenesis. The interaction was detected by BioID analysis combined with co-immunoprecipitation assays.","method":"BioID proximity labeling and co-immunoprecipitation (Co-IP)","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP and BioID used, but GD1 is identified as an interactor rather than being the primary subject; single lab, single study","pmids":["38148574"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"A global barcoded mutant screen in P. berghei identified GD1 (PF3D7_0927200 ortholog) as essential for formation of either male or female sexual forms, with single-cell transcriptomics placing it within a regulatory cascade governing sex determination and differentiation.","method":"Genome-wide barcoded mutant screen (global fitness screen) combined with high-resolution single-cell transcriptomics of mutant parasites","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — barcoded screen validated by single-cell transcriptomics, but the specific mechanistic role of GD1 itself is not resolved beyond essentiality for sexual development","pmids":["36634679"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein that functions as a translational repressor, holding transcripts crucial for gametocyte development in a state of translational repression. GD1 protein levels are regulated by targeted ubiquitination via the PfGID E3 ubiquitin ligase complex, which acts as a substrate of that complex.","method":"Genetic deletion of PfGID complex components, ubiquitination assays, protein level quantification, and functional transmission assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — peer-reviewed study with genetic KO of the E3 ligase, demonstrated ubiquitination of GD1 as substrate, and functional characterization of GD1's translational repression role with multiple orthogonal approaches","pmids":["41986327"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein in P. falciparum gametocytes that functions as a translational repressor of transcripts required for gametocyte development; its protein levels are controlled by targeted ubiquitination via the PfGID E3 ubiquitin ligase complex, and it physically interacts with the CCCH zinc finger protein MD3 as part of a post-transcriptional regulatory complex governing male gametocytogenesis."},"narrative":{"mechanistic_narrative":"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein that acts as a post-transcriptional regulator of sexual development in Plasmodium [PMID:41986327]. In P. falciparum gametocytes it functions as a translational repressor, holding transcripts required for gametocyte development in a translationally repressed state, and its protein abundance is controlled by targeted ubiquitination as a substrate of the PfGID E3 ubiquitin ligase complex [PMID:41986327]. GD1 physically associates with the CCCH zinc finger protein MD3 as part of a regulatory complex implicated in post-transcriptional fine-tuning of male gametocytogenesis [PMID:38148574]. Consistent with a role in sexual differentiation, the P. berghei ortholog is essential for formation of male or female sexual forms and lies within a regulatory cascade governing sex determination [PMID:36634679]. Beyond these findings, the specific transcript targets bound by GD1 and the structural basis of its RNA and complex interactions have not been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing GD1's molecular associations, it was placed within a post-transcriptional regulatory complex by showing it interacts with the CCCH zinc finger protein MD3 in gametocytes.","evidence":"BioID proximity labeling and reciprocal co-immunoprecipitation in P. falciparum gametocytes","pmids":["38148574"],"confidence":"Medium","gaps":["GD1 identified as an interactor rather than the primary subject, so the direction and stoichiometry of the MD3-GD1 association is unresolved","no defined molecular function assigned to GD1 in this study","interaction shown in a single lab/study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"To test whether GD1 is required for sexual development, a genome-wide screen showed the P. berghei ortholog is essential for forming male or female sexual forms and situated it within a sex-determination cascade.","evidence":"Genome-wide barcoded mutant fitness screen with single-cell transcriptomics of mutant parasites in P. berghei","pmids":["36634679"],"confidence":"Medium","gaps":["mechanistic role of GD1 not resolved beyond essentiality","shown in P. berghei ortholog rather than P. falciparum GD1 directly","does not distinguish male- versus female-specific requirement"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"Defining GD1's molecular activity and regulation, GD1 was shown to be a ZFP36 family translational repressor whose protein levels are set by ubiquitination as a substrate of the PfGID E3 ubiquitin ligase complex.","evidence":"Genetic deletion of PfGID complex components, ubiquitination assays, protein-level quantification, and transmission assays in P. falciparum","pmids":["41986327"],"confidence":"High","gaps":["the identity of the specific transcripts repressed by GD1 is not defined","the RNA-binding mode and structural basis of repression are not resolved","how GD1 ubiquitination is temporally coordinated with gametocyte differentiation is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct RNA targets of GD1 and the mechanism linking its MD3 association, PfGID-dependent turnover, and translational repression into a single regulatory logic remain to be defined.","evidence":"","pmids":[],"confidence":"Low","gaps":["no genome-wide identification of GD1-bound transcripts","functional relationship between the MD3 complex and PfGID-mediated turnover unestablished","no structural model of GD1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfGID E3 ubiquitin ligase complex (GD1 acts as substrate) [#2]","MD3-containing post-transcriptional regulatory complex [#0]"],"partners":["MD3 / CCCH ZINC FINGER PROTEIN [#0]","PFGID E3 UBIQUITIN LIGASE COMPLEX [#2]"],"other_free_text":["GD1 is described as a ZFP36 family RNA-binding protein [#2]","Translational repressor holding gametocyte-development transcripts in a repressed state [#2]","P. berghei ortholog is essential for formation of male or female sexual forms [#1]","Implicated in post-transcriptional fine-tuning of male gametocytogenesis via the MD3 complex [#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":"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":["GD1","zinc finger protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41986327","id":"PMC_41986327","title":"GID/CTLH E3 ligase complex control cell fate programs for sexual development of Plasmodium falciparum.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41986327","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GD1"],"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":5984,"output_tokens":935,"usd":0.015988,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5659,"output_tokens":1915,"usd":0.038085,"stage2_stop_reason":"end_turn"},"total_usd":0.054073,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"GD1 (PF3D7_0927200) was identified as a protein interactor of the CCCH zinc finger protein MD3 in P. falciparum gametocytes, as part of a regulatory complex involved in post-transcriptional fine-tuning of male gametocytogenesis. The interaction was detected by BioID analysis combined with co-immunoprecipitation assays.\",\n      \"method\": \"BioID proximity labeling and co-immunoprecipitation (Co-IP)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP and BioID used, but GD1 is identified as an interactor rather than being the primary subject; single lab, single study\",\n      \"pmids\": [\"38148574\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"A global barcoded mutant screen in P. berghei identified GD1 (PF3D7_0927200 ortholog) as essential for formation of either male or female sexual forms, with single-cell transcriptomics placing it within a regulatory cascade governing sex determination and differentiation.\",\n      \"method\": \"Genome-wide barcoded mutant screen (global fitness screen) combined with high-resolution single-cell transcriptomics of mutant parasites\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — barcoded screen validated by single-cell transcriptomics, but the specific mechanistic role of GD1 itself is not resolved beyond essentiality for sexual development\",\n      \"pmids\": [\"36634679\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein that functions as a translational repressor, holding transcripts crucial for gametocyte development in a state of translational repression. GD1 protein levels are regulated by targeted ubiquitination via the PfGID E3 ubiquitin ligase complex, which acts as a substrate of that complex.\",\n      \"method\": \"Genetic deletion of PfGID complex components, ubiquitination assays, protein level quantification, and functional transmission assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — peer-reviewed study with genetic KO of the E3 ligase, demonstrated ubiquitination of GD1 as substrate, and functional characterization of GD1's translational repression role with multiple orthogonal approaches\",\n      \"pmids\": [\"41986327\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein in P. falciparum gametocytes that functions as a translational repressor of transcripts required for gametocyte development; its protein levels are controlled by targeted ubiquitination via the PfGID E3 ubiquitin ligase complex, and it physically interacts with the CCCH zinc finger protein MD3 as part of a post-transcriptional regulatory complex governing male gametocytogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GD1 (PF3D7_0927200) is a ZFP36 family RNA-binding protein that acts as a post-transcriptional regulator of sexual development in Plasmodium [#2]. In P. falciparum gametocytes it functions as a translational repressor, holding transcripts required for gametocyte development in a translationally repressed state, and its protein abundance is controlled by targeted ubiquitination as a substrate of the PfGID E3 ubiquitin ligase complex [#2]. GD1 physically associates with the CCCH zinc finger protein MD3 as part of a regulatory complex implicated in post-transcriptional fine-tuning of male gametocytogenesis [#0]. Consistent with a role in sexual differentiation, the P. berghei ortholog is essential for formation of male or female sexual forms and lies within a regulatory cascade governing sex determination [#1]. Beyond these findings, the specific transcript targets bound by GD1 and the structural basis of its RNA and complex interactions have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing GD1's molecular associations, it was placed within a post-transcriptional regulatory complex by showing it interacts with the CCCH zinc finger protein MD3 in gametocytes.\",\n      \"evidence\": \"BioID proximity labeling and reciprocal co-immunoprecipitation in P. falciparum gametocytes\",\n      \"pmids\": [\"38148574\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GD1 identified as an interactor rather than the primary subject, so the direction and stoichiometry of the MD3-GD1 association is unresolved\", \"no defined molecular function assigned to GD1 in this study\", \"interaction shown in a single lab/study\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To test whether GD1 is required for sexual development, a genome-wide screen showed the P. berghei ortholog is essential for forming male or female sexual forms and situated it within a sex-determination cascade.\",\n      \"evidence\": \"Genome-wide barcoded mutant fitness screen with single-cell transcriptomics of mutant parasites in P. berghei\",\n      \"pmids\": [\"36634679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mechanistic role of GD1 not resolved beyond essentiality\", \"shown in P. berghei ortholog rather than P. falciparum GD1 directly\", \"does not distinguish male- versus female-specific requirement\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defining GD1's molecular activity and regulation, GD1 was shown to be a ZFP36 family translational repressor whose protein levels are set by ubiquitination as a substrate of the PfGID E3 ubiquitin ligase complex.\",\n      \"evidence\": \"Genetic deletion of PfGID complex components, ubiquitination assays, protein-level quantification, and transmission assays in P. falciparum\",\n      \"pmids\": [\"41986327\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"the identity of the specific transcripts repressed by GD1 is not defined\", \"the RNA-binding mode and structural basis of repression are not resolved\", \"how GD1 ubiquitination is temporally coordinated with gametocyte differentiation is unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct RNA targets of GD1 and the mechanism linking its MD3 association, PfGID-dependent turnover, and translational repression into a single regulatory logic remain to be defined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no genome-wide identification of GD1-bound transcripts\", \"functional relationship between the MD3 complex and PfGID-mediated turnover unestablished\", \"no structural model of GD1\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003729\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0030261\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016567\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"PfGID E3 ubiquitin ligase complex (GD1 acts as substrate) [#2]\", \"MD3-containing post-transcriptional regulatory complex [#0]\"],\n    \"partners\": [\"MD3 / CCCH zinc finger protein [#0]\", \"PfGID E3 ubiquitin ligase complex [#2]\"],\n    \"other_free_text\": [\n      \"GD1 is described as a ZFP36 family RNA-binding protein [#2]\",\n      \"Translational repressor holding gametocyte-development transcripts in a repressed state [#2]\",\n      \"P. berghei ortholog is essential for formation of male or female sexual forms [#1]\",\n      \"Implicated in post-transcriptional fine-tuning of male gametocytogenesis via the MD3 complex [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0927200","name":null,"product":"gametocyte development protein GD1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0828000","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0725500","name":null,"product":"zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GD1","evaluation":null}