{"gene":"PF3D7_0104800","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2011,"finding":"NPT1 (PF3D7_0104800 orthologue in P. berghei, PbNPT1) is required for early gametocytogenesis: parasites lacking PbNPT1 are severely compromised in gametocyte production, and the rare gametocytes produced fail to differentiate into fertile gametes, establishing the earliest reverse-genetics block in gametocytogenesis and the first demonstration of a putative transporter protein in sexual development.","method":"Reverse genetics (gene knockout) in P. berghei with phenotypic readout of gametocyte production and gamete differentiation","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (gametocyte production and gamete differentiation), single lab, single method","pmids":["21752110"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"finding":"PbNPT1 (the P. berghei orthologue of NPT1/PF3D7_0104800) functions as a cationic amino acid transporter, consistent with a role in scavenging cationic amino acids during the gametocyte stage.","method":"Functional transport assay (heterologous expression system) demonstrating cationic amino acid transport activity for PbNPT1","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro transport assay in heterologous system for PbNPT1, single lab, single paper; the specific assay details for PbNPT1 are compressed in the abstract","pmids":["28205520"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"PfNPT1 (PF3D7_0104800) localizes to the parasite plasma membrane in P. falciparum late schizonts and is identified as a potential substrate of PfCDPK5, with phosphorylation at specific sites significantly reduced in PfCDPK5-deficient parasites as detected by quantitative phosphoproteomics.","method":"Label-free quantitative phosphoproteomic profiling of tightly synchronized late schizonts under conditional knockdown of PfCDPK5; subcellular localization by direct imaging","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative phosphoproteomics with conditional knockdown and direct localization, single lab, two orthogonal methods (phosphoproteomics + localization imaging)","pmids":["31915223"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0104800 (NPT1) encodes a plasma-membrane-localized putative cationic amino acid transporter in Plasmodium: its P. berghei orthologue (PbNPT1) is essential for early gametocytogenesis and gamete differentiation and has demonstrated cationic amino acid transport activity in heterologous systems, while P. falciparum PfNPT1 localizes to the parasite plasma membrane at the late schizont stage and is a candidate substrate of the egress kinase PfCDPK5."},"narrative":{"mechanistic_narrative":"NPT1 (PF3D7_0104800) is a putative plasma-membrane transporter implicated in Plasmodium amino acid acquisition and sexual development. In P. berghei, the orthologue PbNPT1 is required for early gametocytogenesis: its knockout severely compromises gametocyte production and prevents the rare surviving gametocytes from differentiating into fertile gametes, marking one of the earliest reverse-genetics blocks in the sexual pathway [PMID:21752110]. Functional assays in a heterologous system show that PbNPT1 transports cationic amino acids, consistent with a scavenging role at the gametocyte stage [PMID:28205520]. In P. falciparum, PfNPT1 localizes to the parasite plasma membrane in late schizonts and is a candidate substrate of the egress kinase PfCDPK5, with phosphorylation at specific sites reduced upon PfCDPK5 knockdown [PMID:31915223]. Beyond these findings, the transport mechanism, substrate specificity in P. falciparum, and the functional consequence of its phosphorylation have not been characterized in the available corpus.","teleology":[{"year":2011,"claim":"To determine whether a putative transporter contributes to Plasmodium sexual development, knockout established that NPT1 is required for early gametocytogenesis and gamete differentiation.","evidence":"Gene knockout in P. berghei with phenotypic readout of gametocyte production and gamete fertility","pmids":["21752110"],"confidence":"Medium","gaps":["Does not define the transported substrate or the molecular basis of the developmental block","Single lab, single method; phenotype not shown for the P. falciparum orthologue","Whether the defect is cell-autonomous to the transporter's activity is not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"To assign a biochemical activity to the developmentally essential protein, heterologous transport assays showed PbNPT1 transports cationic amino acids, linking the gametocyte phenotype to a scavenging function.","evidence":"Functional transport assay in a heterologous expression system for PbNPT1","pmids":["28205520"],"confidence":"Medium","gaps":["In vitro heterologous assay; endogenous substrate range and kinetics in the parasite not established","Direct transport activity not demonstrated for the P. falciparum protein","Assay details compressed; directionality and driving forces unclear"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"To place the P. falciparum protein in a cellular context, phosphoproteomics and imaging localized PfNPT1 to the plasma membrane of late schizonts and identified it as a candidate PfCDPK5 substrate.","evidence":"Label-free quantitative phosphoproteomics under conditional PfCDPK5 knockdown plus direct localization imaging in synchronized late schizonts","pmids":["31915223"],"confidence":"Medium","gaps":["Candidate substrate relationship is correlative; direct kinase-substrate phosphorylation not reconstituted","Functional consequence of the phosphorylation on transport or egress not tested","Whether P. falciparum NPT1 has a sexual-stage role like the P. berghei orthologue is not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether phosphorylation of PfNPT1 by PfCDPK5 regulates its transport activity and how cationic amino acid transport connects mechanistically to gametocytogenesis remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct link between phosphorylation state and transporter function","P. falciparum transport activity and substrate specificity uncharacterized","Mechanistic connection between amino acid scavenging and the gametocyte differentiation block unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFCDPK5 (CANDIDATE UPSTREAM KINASE PHOSPHORYLATING PFNPT1)"],"other_free_text":["P. berghei orthologue PbNPT1 knockout blocks early gametocytogenesis and gamete differentiation [#0].","PbNPT1 shows cationic amino acid transport activity in a heterologous system [#1].","P. falciparum PfNPT1 localizes to the parasite plasma membrane in late schizonts and is a candidate PfCDPK5 substrate [#2]."]}},"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":"28205520","id":"PMC_28205520","title":"Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28205520","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbNPT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21752110","id":"PMC_21752110","title":"The novel putative transporter NPT1 plays a critical role in early stages of Plasmodium berghei sexual development.","date":"2011","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21752110","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NPT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31915223","id":"PMC_31915223","title":"Influence of Plasmodium falciparum Calcium-Dependent Protein Kinase 5 (PfCDPK5) on the Late Schizont Stage Phosphoproteome.","date":"2020","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/31915223","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfNPT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39905186","id":"PMC_39905186","title":"Characteristics of Plasmodium vivax apicomplexan amino acid transporter 8 (PvApiAT8) in the cationic amino acid transport.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39905186","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NPT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40032183","id":"PMC_40032183","title":"Structural and functional implications of MIT2 and NT2 mutations in amodiaquine and piperaquine resistant Plasmodium berghei parasites.","date":"2025","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/40032183","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NPT1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6112,"output_tokens":960,"usd":0.016368,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5670,"output_tokens":1867,"usd":0.037512,"stage2_stop_reason":"end_turn"},"total_usd":0.05388,"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\": 2011,\n      \"finding\": \"NPT1 (PF3D7_0104800 orthologue in P. berghei, PbNPT1) is required for early gametocytogenesis: parasites lacking PbNPT1 are severely compromised in gametocyte production, and the rare gametocytes produced fail to differentiate into fertile gametes, establishing the earliest reverse-genetics block in gametocytogenesis and the first demonstration of a putative transporter protein in sexual development.\",\n      \"method\": \"Reverse genetics (gene knockout) in P. berghei with phenotypic readout of gametocyte production and gamete differentiation\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (gametocyte production and gamete differentiation), single lab, single method\",\n      \"pmids\": [\"21752110\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PbNPT1 (the P. berghei orthologue of NPT1/PF3D7_0104800) functions as a cationic amino acid transporter, consistent with a role in scavenging cationic amino acids during the gametocyte stage.\",\n      \"method\": \"Functional transport assay (heterologous expression system) demonstrating cationic amino acid transport activity for PbNPT1\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro transport assay in heterologous system for PbNPT1, single lab, single paper; the specific assay details for PbNPT1 are compressed in the abstract\",\n      \"pmids\": [\"28205520\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PfNPT1 (PF3D7_0104800) localizes to the parasite plasma membrane in P. falciparum late schizonts and is identified as a potential substrate of PfCDPK5, with phosphorylation at specific sites significantly reduced in PfCDPK5-deficient parasites as detected by quantitative phosphoproteomics.\",\n      \"method\": \"Label-free quantitative phosphoproteomic profiling of tightly synchronized late schizonts under conditional knockdown of PfCDPK5; subcellular localization by direct imaging\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative phosphoproteomics with conditional knockdown and direct localization, single lab, two orthogonal methods (phosphoproteomics + localization imaging)\",\n      \"pmids\": [\"31915223\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0104800 (NPT1) encodes a plasma-membrane-localized putative cationic amino acid transporter in Plasmodium: its P. berghei orthologue (PbNPT1) is essential for early gametocytogenesis and gamete differentiation and has demonstrated cationic amino acid transport activity in heterologous systems, while P. falciparum PfNPT1 localizes to the parasite plasma membrane at the late schizont stage and is a candidate substrate of the egress kinase PfCDPK5.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NPT1 (PF3D7_0104800) is a putative plasma-membrane transporter implicated in Plasmodium amino acid acquisition and sexual development. In P. berghei, the orthologue PbNPT1 is required for early gametocytogenesis: its knockout severely compromises gametocyte production and prevents the rare surviving gametocytes from differentiating into fertile gametes, marking one of the earliest reverse-genetics blocks in the sexual pathway [#0]. Functional assays in a heterologous system show that PbNPT1 transports cationic amino acids, consistent with a scavenging role at the gametocyte stage [#1]. In P. falciparum, PfNPT1 localizes to the parasite plasma membrane in late schizonts and is a candidate substrate of the egress kinase PfCDPK5, with phosphorylation at specific sites reduced upon PfCDPK5 knockdown [#2]. Beyond these findings, the transport mechanism, substrate specificity in P. falciparum, and the functional consequence of its phosphorylation have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"To determine whether a putative transporter contributes to Plasmodium sexual development, knockout established that NPT1 is required for early gametocytogenesis and gamete differentiation.\",\n      \"evidence\": \"Gene knockout in P. berghei with phenotypic readout of gametocyte production and gamete fertility\",\n      \"pmids\": [\"21752110\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not define the transported substrate or the molecular basis of the developmental block\",\n        \"Single lab, single method; phenotype not shown for the P. falciparum orthologue\",\n        \"Whether the defect is cell-autonomous to the transporter's activity is not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To assign a biochemical activity to the developmentally essential protein, heterologous transport assays showed PbNPT1 transports cationic amino acids, linking the gametocyte phenotype to a scavenging function.\",\n      \"evidence\": \"Functional transport assay in a heterologous expression system for PbNPT1\",\n      \"pmids\": [\"28205520\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"In vitro heterologous assay; endogenous substrate range and kinetics in the parasite not established\",\n        \"Direct transport activity not demonstrated for the P. falciparum protein\",\n        \"Assay details compressed; directionality and driving forces unclear\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To place the P. falciparum protein in a cellular context, phosphoproteomics and imaging localized PfNPT1 to the plasma membrane of late schizonts and identified it as a candidate PfCDPK5 substrate.\",\n      \"evidence\": \"Label-free quantitative phosphoproteomics under conditional PfCDPK5 knockdown plus direct localization imaging in synchronized late schizonts\",\n      \"pmids\": [\"31915223\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Candidate substrate relationship is correlative; direct kinase-substrate phosphorylation not reconstituted\",\n        \"Functional consequence of the phosphorylation on transport or egress not tested\",\n        \"Whether P. falciparum NPT1 has a sexual-stage role like the P. berghei orthologue is not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether phosphorylation of PfNPT1 by PfCDPK5 regulates its transport activity and how cationic amino acid transport connects mechanistically to gametocytogenesis remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct link between phosphorylation state and transporter function\",\n        \"P. falciparum transport activity and substrate specificity uncharacterized\",\n        \"Mechanistic connection between amino acid scavenging and the gametocyte differentiation block unresolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0015171\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020039\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0060065\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfCDPK5 (candidate upstream kinase phosphorylating PfNPT1)\"],\n    \"other_free_text\": [\n      \"P. berghei orthologue PbNPT1 knockout blocks early gametocytogenesis and gamete differentiation [#0].\",\n      \"PbNPT1 shows cationic amino acid transport activity in a heterologous system [#1].\",\n      \"P. falciparum PfNPT1 localizes to the parasite plasma membrane in late schizonts and is a candidate PfCDPK5 substrate [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0104800","name":null,"product":"novel putative transporter 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0208300","name":null,"product":"novel putative transporter 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0208700","name":null,"product":"novel putative transporter 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NPT1","evaluation":null}