{"gene":"PF3D7_0103100","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2023,"finding":"VPS51 (PF3D7_0103100) tagged endogenously with 2xFKBP-GFP-2xFKBP showed GFP foci in the parasite cytosol without consistent overlap with mCherry-K13 foci in ring and trophozoite stages, indicating that VPS51 does not localize to the K13 compartment.","method":"Endogenous C-terminal tagging (2xFKBP-GFP-2xFKBP) combined with fluorescence microscopy and co-expression of mCherry-K13","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment with endogenous tagging, single lab, single method","pmids":["38039338"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Targeted gene disruption of vps51 (PF3D7_0103100) was successfully generated, indicating that VPS51 is dispensable for in vitro asexual parasite proliferation.","method":"Targeted gene disruption (knockout) with in vitro growth assay","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean genetic knockout with defined growth phenotype readout, single lab, single method","pmids":["38039338"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"VPS51 (PF3D7_0103100) was identified as a proximity biotinylation hit in BioID experiments using K13 or Eps15 as bait, placing it in the broader K13 compartment candidate protein network, though subsequent localization did not confirm it as a K13 compartment protein.","method":"Proximity-dependent biotinylation (BioID) using K13 and Eps15 as baits","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proximity-labeling experiment, not confirmed by downstream localization as a true K13 compartment protein","pmids":["38039338"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"VPS51 (PF3D7_0103100) transcript is upregulated in the pt1 pseudotime cluster during P. falciparum development from early zygote to ookinete in the mosquito midgut, suggesting a potential role in vesicle sorting and protein transport during this stage transition.","method":"Single-cell transcriptomics","journal":"Microbiology spectrum","confidence":"Low","confidence_rationale":"Tier 4 / Weak — transcriptomic expression data only, no functional or protein-level validation","pmids":["36847501"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Bioinformatic analysis identified a VPS51 homolog in P. falciparum as part of the GARP/VFT complex within the broader multi-subunit tethering complex (MTC) complement, consistent with a role in vesicle-target interactions; however, conservation of HOPS/CORVET-specific subunits including VPS51 was found to be sparse across apicomplexan genomes.","method":"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic analysis only, no functional experimental validation of PF3D7_0103100 specifically","pmids":["24086721"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0103100 (VPS51) localizes to cytosolic foci in P. falciparum asexual blood stages but does not co-localize with the K13 compartment, is dispensable for in vitro asexual growth as demonstrated by successful gene disruption, and was identified as a proximity-biotinylation hit near K13/Eps15; its transcript is upregulated during early ookinete development, but no direct enzymatic activity, binding partner, or defined trafficking role has been experimentally established for this protein."},"narrative":{"mechanistic_narrative":"PF3D7_0103100 (VPS51) is a Plasmodium falciparum protein of largely uncharacterized function that, based on endogenous tagging, localizes to discrete foci in the parasite cytosol during asexual blood-stage development without consistent overlap with the K13 compartment [PMID:38039338]. It is dispensable for in vitro asexual proliferation, as targeted gene disruption yielded viable parasites [PMID:38039338]. VPS51 was recovered as a proximity-biotinylation hit using K13 and Eps15 as baits, placing it near, but not within, the K13 compartment protein network [PMID:38039338]. Beyond this cytosolic focal localization and its dispensability for asexual growth, no direct enzymatic activity, binding partner, or defined trafficking role has been experimentally established for PF3D7_0103100 in the available corpus; its proposed membership in a GARP/VFT-type multi-subunit tethering complex rests on bioinformatic inference rather than functional data [PMID:24086721], and its transcript upregulation during zygote-to-ookinete development is transcriptomic only [PMID:36847501].","teleology":[{"year":2013,"claim":"The first question was whether P. falciparum even encodes a VPS51-like tethering subunit, establishing candidate membership in a multi-subunit tethering complex.","evidence":"Comparative genomic analysis across 12 apicomplexan genomes","pmids":["24086721"],"confidence":"Low","gaps":["Computational inference only; no protein-level or functional validation of PF3D7_0103100","Reported sparse conservation of complex subunits across apicomplexa leaves complex assembly unconfirmed","No demonstrated binding partners for the predicted complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Single-cell transcriptomics addressed when VPS51 is expressed, revealing stage-specific upregulation during early mosquito-stage development.","evidence":"Single-cell transcriptomics across zygote-to-ookinete pseudotime","pmids":["36847501"],"confidence":"Low","gaps":["Transcript-level data only, no protein or functional validation","Does not establish any trafficking role during the stage transition","No causal link between VPS51 expression and ookinete development"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Endogenous tagging and knockout tested where VPS51 acts and whether it is required, showing cytosolic foci distinct from the K13 compartment and dispensability for asexual growth.","evidence":"Endogenous 2xFKBP-GFP-2xFKBP tagging with fluorescence microscopy plus targeted gene disruption and in vitro growth assay","pmids":["38039338"],"confidence":"Medium","gaps":["The identity and function of the cytosolic foci are undefined","No binding partner or cargo established for VPS51","Dispensability tested only for in vitro asexual stages; sexual/mosquito-stage roles untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Proximity biotinylation asked whether VPS51 belongs to the K13 compartment network, placing it near K13/Eps15 but not confirming it as a bona fide K13 compartment protein.","evidence":"Proximity-dependent biotinylation (BioID) with K13 and Eps15 as baits","pmids":["38039338"],"confidence":"Low","gaps":["Single proximity-labeling experiment not corroborated by localization","Proximity does not establish direct interaction with K13 or Eps15","Functional relevance of the association is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The core molecular function of VPS51 remains open: no direct binding partner, tethering-complex assembly, cargo, or trafficking role has been experimentally demonstrated for PF3D7_0103100.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical confirmation of GARP/VFT or other tethering-complex membership","Nature and cargo of the cytosolic foci undefined","No functional test in sexual or mosquito stages despite stage-specific transcript upregulation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GARP/VFT multi-subunit tethering complex (bioinformatic inference only) [#4]"],"partners":["K13 (PROXIMITY-BIOTINYLATION ONLY, NOT CONFIRMED AS DIRECT INTERACTOR) [#2]","EPS15 (PROXIMITY-BIOTINYLATION ONLY, NOT CONFIRMED AS DIRECT INTERACTOR) [#2]"],"other_free_text":["Dispensable for in vitro asexual blood-stage proliferation (viable gene disruption) [#1]","Localizes to cytosolic foci that do not overlap the K13 compartment [#0]","Transcript upregulated during zygote-to-ookinete development in the mosquito midgut [#3]","No direct enzymatic activity, cargo, or trafficking function experimentally established for PF3D7_0103100"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24086721","id":"PMC_24086721","title":"Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24086721","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42115185","id":"","title":"Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42115185","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS51"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37681888","id":"","title":"Camillo Golgi's Impact on Malaria Studies.","date":"2023","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/37681888","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS51"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38039338","id":"","title":"The Kelch13 compartment contains highly divergent vesicle trafficking proteins in malaria parasites.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38039338","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS51"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36847501","id":"","title":"Single-Cell Transcriptomics To Define Plasmodium falciparum Stage Transition in the Mosquito Midgut.","date":"2023","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36847501","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["VPS51"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7744,"output_tokens":1308,"usd":0.021426,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6163,"output_tokens":2115,"usd":0.041845,"stage2_stop_reason":"end_turn"},"total_usd":0.063271,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"VPS51 (PF3D7_0103100) tagged endogenously with 2xFKBP-GFP-2xFKBP showed GFP foci in the parasite cytosol without consistent overlap with mCherry-K13 foci in ring and trophozoite stages, indicating that VPS51 does not localize to the K13 compartment.\",\n      \"method\": \"Endogenous C-terminal tagging (2xFKBP-GFP-2xFKBP) combined with fluorescence microscopy and co-expression of mCherry-K13\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment with endogenous tagging, single lab, single method\",\n      \"pmids\": [\"38039338\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Targeted gene disruption of vps51 (PF3D7_0103100) was successfully generated, indicating that VPS51 is dispensable for in vitro asexual parasite proliferation.\",\n      \"method\": \"Targeted gene disruption (knockout) with in vitro growth assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean genetic knockout with defined growth phenotype readout, single lab, single method\",\n      \"pmids\": [\"38039338\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"VPS51 (PF3D7_0103100) was identified as a proximity biotinylation hit in BioID experiments using K13 or Eps15 as bait, placing it in the broader K13 compartment candidate protein network, though subsequent localization did not confirm it as a K13 compartment protein.\",\n      \"method\": \"Proximity-dependent biotinylation (BioID) using K13 and Eps15 as baits\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proximity-labeling experiment, not confirmed by downstream localization as a true K13 compartment protein\",\n      \"pmids\": [\"38039338\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"VPS51 (PF3D7_0103100) transcript is upregulated in the pt1 pseudotime cluster during P. falciparum development from early zygote to ookinete in the mosquito midgut, suggesting a potential role in vesicle sorting and protein transport during this stage transition.\",\n      \"method\": \"Single-cell transcriptomics\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — transcriptomic expression data only, no functional or protein-level validation\",\n      \"pmids\": [\"36847501\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Bioinformatic analysis identified a VPS51 homolog in P. falciparum as part of the GARP/VFT complex within the broader multi-subunit tethering complex (MTC) complement, consistent with a role in vesicle-target interactions; however, conservation of HOPS/CORVET-specific subunits including VPS51 was found to be sparse across apicomplexan genomes.\",\n      \"method\": \"Comparative genomic/bioinformatic analysis across 12 apicomplexan genomes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic analysis only, no functional experimental validation of PF3D7_0103100 specifically\",\n      \"pmids\": [\"24086721\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0103100 (VPS51) localizes to cytosolic foci in P. falciparum asexual blood stages but does not co-localize with the K13 compartment, is dispensable for in vitro asexual growth as demonstrated by successful gene disruption, and was identified as a proximity-biotinylation hit near K13/Eps15; its transcript is upregulated during early ookinete development, but no direct enzymatic activity, binding partner, or defined trafficking role has been experimentally established for this protein.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0103100 (VPS51) is a Plasmodium falciparum protein of largely uncharacterized function that, based on endogenous tagging, localizes to discrete foci in the parasite cytosol during asexual blood-stage development without consistent overlap with the K13 compartment [#0]. It is dispensable for in vitro asexual proliferation, as targeted gene disruption yielded viable parasites [#1]. VPS51 was recovered as a proximity-biotinylation hit using K13 and Eps15 as baits, placing it near, but not within, the K13 compartment protein network [#2]. Beyond this cytosolic focal localization and its dispensability for asexual growth, no direct enzymatic activity, binding partner, or defined trafficking role has been experimentally established for PF3D7_0103100 in the available corpus; its proposed membership in a GARP/VFT-type multi-subunit tethering complex rests on bioinformatic inference rather than functional data [#4], and its transcript upregulation during zygote-to-ookinete development is transcriptomic only [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"The first question was whether P. falciparum even encodes a VPS51-like tethering subunit, establishing candidate membership in a multi-subunit tethering complex.\",\n      \"evidence\": \"Comparative genomic analysis across 12 apicomplexan genomes\",\n      \"pmids\": [\"24086721\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational inference only; no protein-level or functional validation of PF3D7_0103100\",\n        \"Reported sparse conservation of complex subunits across apicomplexa leaves complex assembly unconfirmed\",\n        \"No demonstrated binding partners for the predicted complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Single-cell transcriptomics addressed when VPS51 is expressed, revealing stage-specific upregulation during early mosquito-stage development.\",\n      \"evidence\": \"Single-cell transcriptomics across zygote-to-ookinete pseudotime\",\n      \"pmids\": [\"36847501\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcript-level data only, no protein or functional validation\",\n        \"Does not establish any trafficking role during the stage transition\",\n        \"No causal link between VPS51 expression and ookinete development\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Endogenous tagging and knockout tested where VPS51 acts and whether it is required, showing cytosolic foci distinct from the K13 compartment and dispensability for asexual growth.\",\n      \"evidence\": \"Endogenous 2xFKBP-GFP-2xFKBP tagging with fluorescence microscopy plus targeted gene disruption and in vitro growth assay\",\n      \"pmids\": [\"38039338\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The identity and function of the cytosolic foci are undefined\",\n        \"No binding partner or cargo established for VPS51\",\n        \"Dispensability tested only for in vitro asexual stages; sexual/mosquito-stage roles untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Proximity biotinylation asked whether VPS51 belongs to the K13 compartment network, placing it near K13/Eps15 but not confirming it as a bona fide K13 compartment protein.\",\n      \"evidence\": \"Proximity-dependent biotinylation (BioID) with K13 and Eps15 as baits\",\n      \"pmids\": [\"38039338\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single proximity-labeling experiment not corroborated by localization\",\n        \"Proximity does not establish direct interaction with K13 or Eps15\",\n        \"Functional relevance of the association is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core molecular function of VPS51 remains open: no direct binding partner, tethering-complex assembly, cargo, or trafficking role has been experimentally demonstrated for PF3D7_0103100.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No biochemical confirmation of GARP/VFT or other tethering-complex membership\",\n        \"Nature and cargo of the cytosolic foci undefined\",\n        \"No functional test in sexual or mosquito stages despite stage-specific transcript upregulation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"GARP/VFT multi-subunit tethering complex (bioinformatic inference only) [#4]\"\n    ],\n    \"partners\": [\n      \"K13 (proximity-biotinylation only, not confirmed as direct interactor) [#2]\",\n      \"Eps15 (proximity-biotinylation only, not confirmed as direct interactor) [#2]\"\n    ],\n    \"other_free_text\": [\n      \"Dispensable for in vitro asexual blood-stage proliferation (viable gene disruption) [#1]\",\n      \"Localizes to cytosolic foci that do not overlap the K13 compartment [#0]\",\n      \"Transcript upregulated during zygote-to-ookinete development in the mosquito midgut [#3]\",\n      \"No direct enzymatic activity, cargo, or trafficking function experimentally established for PF3D7_0103100\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0103100","name":null,"product":"vacuolar protein sorting-associated protein 51, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0210000","name":null,"product":"vacuolar protein sorting-associated protein 51, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0210500","name":null,"product":"vacuolar protein sorting-associated protein 51, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"VPS51","evaluation":null}