{"gene":"PF3D7_0319000","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2016,"finding":"ATPase7 (PF3D7_0319000 ortholog in P. berghei) is refractory to gene deletion, indicating an essential function during the parasite life cycle in mice and Anopheles mosquitoes. It is classified as a candidate aminophospholipid transporter.","method":"Comprehensive genetic screen; attempted gene deletion with failure indicating essentiality","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO attempt with defined phenotypic readout (refractory to deletion), single study but part of a systematic genome-wide genetic analysis of 35 transporters","pmids":["26796412"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"finding":"ATPase7 (P4-ATPase) in P. yoelii localizes to the ookinete plasma membrane, interacts with the flippase cofactor CDC50C, and is required for phosphatidylcholine translocation (flippase activity) across the plasma membrane. Disruption of ATP7 blocks mosquito infection by causing ookinete elimination within midgut epithelial cells via a complement-independent mechanism; ookinetes lacking ATP7 can invade the midgut but cannot survive traversal. Microinjection of ATP7-depleted ookinetes into the mosquito hemocoel reverses the transmission defect, confirming the function is specifically required during midgut epithelium traversal.","method":"Gene disruption (knockout), live fluorescence localization, co-immunoprecipitation (interaction with CDC50C), phospholipid uptake assay, ookinete microinjection rescue experiment","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods in a single study: genetic KO with defined phenotype, direct localization, Co-IP, phospholipid uptake functional assay, and rescue by microinjection","pmids":["34301597"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"ATPase7 (PF3D7_0319000) is a P4-type ATPase phospholipid flippase that localizes to the ookinete plasma membrane, forms a complex with the cofactor CDC50C, and mediates phosphatidylcholine translocation across the bilayer; this flippase activity is essential for ookinete survival during mosquito midgut epithelium traversal and thus for parasite transmission, and the ortholog in P. berghei is also refractory to gene deletion indicating broader essentiality across the life cycle."},"narrative":{"mechanistic_narrative":"ATPase7 (PF3D7_0319000) is a P4-type ATPase phospholipid flippase that operates at the ookinete plasma membrane to enable Plasmodium transmission through the mosquito midgut [PMID:34301597]. In P. yoelii, ATPase7 localizes to the ookinete plasma membrane, forms a complex with the flippase cofactor CDC50C, and drives inward translocation of phosphatidylcholine across the bilayer [PMID:34301597]. This flippase activity is specifically required for ookinete survival during traversal of the midgut epithelium: parasites lacking ATPase7 invade the midgut but are eliminated within epithelial cells by a complement-independent mechanism, and microinjecting depleted ookinetes directly into the hemocoel bypasses the block and restores transmission [PMID:34301597]. Consistent with an essential role, the P. berghei ortholog is refractory to gene deletion [PMID:26796412]. Beyond these findings, no further mechanistic detail for ATPase7 has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Whether ATPase7 is dispensable was unknown; a systematic deletion screen established that it is essential and provisionally a lipid transporter.","evidence":"Genome-wide genetic screen of transporters with attempted gene deletion in P. berghei","pmids":["26796412"],"confidence":"Medium","gaps":["Refractoriness to deletion does not identify the essential stage or the molecular activity","No localization, substrate, or partner defined","Aminophospholipid transporter classification was inferred, not demonstrated"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"claim":"The molecular activity and stage-specific requirement were unknown; multiple orthogonal experiments established ATPase7 as a CDC50C-partnered phosphatidylcholine flippase at the ookinete plasma membrane required for surviving midgut epithelium traversal.","evidence":"Gene knockout, live fluorescence localization, co-immunoprecipitation with CDC50C, phospholipid uptake assay, and hemocoel microinjection rescue in P. yoelii","pmids":["34301597"],"confidence":"High","gaps":["Structural basis of ATP-driven phospholipid translocation not resolved","How loss of PC flipping triggers ookinete elimination within epithelial cells is undefined","Whether functions are conserved in the human parasite P. falciparum (PF3D7_0319000 itself) not directly tested"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"It remains unknown whether ATPase7 has functions in blood-stage or other life-cycle stages beyond the ookinete, and what structural features couple ATP hydrolysis to phospholipid transport.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No blood-stage functional data in the corpus","No structural or catalytic mechanism characterized","No direct characterization of the P. falciparum PF3D7_0319000 protein"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ATPase7–CDC50C flippase complex"],"partners":["CDC50C"],"other_free_text":["Essential for Plasmodium transmission; ookinetes lacking ATPase7 invade the mosquito midgut but are eliminated within epithelial cells via a complement-independent mechanism during traversal [#1]","Transmission defect of ATPase7-depleted ookinetes is rescued by direct microinjection into the mosquito hemocoel, localizing the requirement to midgut epithelium traversal [#1]","P. berghei ortholog is refractory to gene deletion, indicating essentiality [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15774027","id":"PMC_15774027","title":"The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum.","date":"2005","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/15774027","citation_count":146,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26796412","id":"PMC_26796412","title":"Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26796412","citation_count":75,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34301597","id":"PMC_34301597","title":"A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/34301597","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4059,"output_tokens":755,"usd":0.011751,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5412,"output_tokens":1662,"usd":0.034305,"stage2_stop_reason":"end_turn"},"total_usd":0.046056,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"ATPase7 (PF3D7_0319000 ortholog in P. berghei) is refractory to gene deletion, indicating an essential function during the parasite life cycle in mice and Anopheles mosquitoes. It is classified as a candidate aminophospholipid transporter.\",\n      \"method\": \"Comprehensive genetic screen; attempted gene deletion with failure indicating essentiality\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO attempt with defined phenotypic readout (refractory to deletion), single study but part of a systematic genome-wide genetic analysis of 35 transporters\",\n      \"pmids\": [\"26796412\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"ATPase7 (P4-ATPase) in P. yoelii localizes to the ookinete plasma membrane, interacts with the flippase cofactor CDC50C, and is required for phosphatidylcholine translocation (flippase activity) across the plasma membrane. Disruption of ATP7 blocks mosquito infection by causing ookinete elimination within midgut epithelial cells via a complement-independent mechanism; ookinetes lacking ATP7 can invade the midgut but cannot survive traversal. Microinjection of ATP7-depleted ookinetes into the mosquito hemocoel reverses the transmission defect, confirming the function is specifically required during midgut epithelium traversal.\",\n      \"method\": \"Gene disruption (knockout), live fluorescence localization, co-immunoprecipitation (interaction with CDC50C), phospholipid uptake assay, ookinete microinjection rescue experiment\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods in a single study: genetic KO with defined phenotype, direct localization, Co-IP, phospholipid uptake functional assay, and rescue by microinjection\",\n      \"pmids\": [\"34301597\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ATPase7 (PF3D7_0319000) is a P4-type ATPase phospholipid flippase that localizes to the ookinete plasma membrane, forms a complex with the cofactor CDC50C, and mediates phosphatidylcholine translocation across the bilayer; this flippase activity is essential for ookinete survival during mosquito midgut epithelium traversal and thus for parasite transmission, and the ortholog in P. berghei is also refractory to gene deletion indicating broader essentiality across the life cycle.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ATPase7 (PF3D7_0319000) is a P4-type ATPase phospholipid flippase that operates at the ookinete plasma membrane to enable Plasmodium transmission through the mosquito midgut [#1]. In P. yoelii, ATPase7 localizes to the ookinete plasma membrane, forms a complex with the flippase cofactor CDC50C, and drives inward translocation of phosphatidylcholine across the bilayer [#1]. This flippase activity is specifically required for ookinete survival during traversal of the midgut epithelium: parasites lacking ATPase7 invade the midgut but are eliminated within epithelial cells by a complement-independent mechanism, and microinjecting depleted ookinetes directly into the hemocoel bypasses the block and restores transmission [#1]. Consistent with an essential role, the P. berghei ortholog is refractory to gene deletion [#0]. Beyond these findings, no further mechanistic detail for ATPase7 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether ATPase7 is dispensable was unknown; a systematic deletion screen established that it is essential and provisionally a lipid transporter.\",\n      \"evidence\": \"Genome-wide genetic screen of transporters with attempted gene deletion in P. berghei\",\n      \"pmids\": [\"26796412\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Refractoriness to deletion does not identify the essential stage or the molecular activity\",\n        \"No localization, substrate, or partner defined\",\n        \"Aminophospholipid transporter classification was inferred, not demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The molecular activity and stage-specific requirement were unknown; multiple orthogonal experiments established ATPase7 as a CDC50C-partnered phosphatidylcholine flippase at the ookinete plasma membrane required for surviving midgut epithelium traversal.\",\n      \"evidence\": \"Gene knockout, live fluorescence localization, co-immunoprecipitation with CDC50C, phospholipid uptake assay, and hemocoel microinjection rescue in P. yoelii\",\n      \"pmids\": [\"34301597\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of ATP-driven phospholipid translocation not resolved\",\n        \"How loss of PC flipping triggers ookinete elimination within epithelial cells is undefined\",\n        \"Whether functions are conserved in the human parasite P. falciparum (PF3D7_0319000 itself) not directly tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether ATPase7 has functions in blood-stage or other life-cycle stages beyond the ookinete, and what structural features couple ATP hydrolysis to phospholipid transport.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No blood-stage functional data in the corpus\",\n        \"No structural or catalytic mechanism characterized\",\n        \"No direct characterization of the P. falciparum PF3D7_0319000 protein\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004012\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0140326\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0045332\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"ATPase7–CDC50C flippase complex\"\n    ],\n    \"partners\": [\n      \"CDC50C\"\n    ],\n    \"other_free_text\": [\n      \"Essential for Plasmodium transmission; ookinetes lacking ATPase7 invade the mosquito midgut but are eliminated within epithelial cells via a complement-independent mechanism during traversal [#1]\",\n      \"Transmission defect of ATPase7-depleted ookinetes is rescued by direct microinjection into the mosquito hemocoel, localizing the requirement to midgut epithelium traversal [#1]\",\n      \"P. berghei ortholog is refractory to gene deletion, indicating essentiality [#0]\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_0319000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_1029400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0319000","name":null,"product":"P4-type ATPase ATP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0806300","name":null,"product":"P4-type ATPase ATP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0822500","name":null,"product":"P4-type ATPase ATP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATPase7","evaluation":null}