{"gene":"PF3D7_1211500","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2020,"finding":"PF3D7_1211500 (mtRPS18/PfmtRPS18), a small subunit mitoribosomal protein, was verified by immuno-EM to localize within the mitochondrion and shown to be essential for parasite viability in P. falciparum; conditional CRISPR/Cas9-based knockdown demonstrated that loss of mtRPS18 (along with other small subunit proteins PfmtRPS12 and PfmtRPS17) compromises mitochondrial membrane potential and causes hypersensitivity to inhibitors of Complex III (bc1), DHODH, and F1F0-ATP synthase, and blocks pyrimidine biosynthesis by reducing the cellular pool of pyrimidine nucleotides.","method":"CRISPR/Cas9-based conditional knockdown, immuno-electron microscopy, drug sensitivity assays, metabolite profiling","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined cellular and metabolic phenotypes plus immuno-EM localization, single lab, multiple orthogonal readouts but no in vitro reconstitution or structural validation of mtRPS18 specifically","pmids":["32273345"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, mtRPS18 (PF3D7_1211500) is an essential component of the mitochondrial small ribosomal subunit that localizes to the inner mitochondrial membrane; its loss disrupts mitoribosome function, collapses mitochondrial membrane potential, blocks pyrimidine biosynthesis, and renders parasites hypersensitive to inhibitors targeting mitochondrial electron transport and the F1F0-ATP synthase."},"narrative":{"mechanistic_narrative":"In P. falciparum, mtRPS18 (PF3D7_1211500) is an essential small-subunit mitoribosomal protein required for mitochondrial function and parasite viability [PMID:32273345]. Immuno-electron microscopy localizes mtRPS18 within the mitochondrion, and conditional CRISPR/Cas9 knockdown collapses the mitochondrial membrane potential, blocks pyrimidine biosynthesis by depleting cellular pyrimidine nucleotide pools, and renders parasites hypersensitive to inhibitors of Complex III (bc1), DHODH, and the F1F0-ATP synthase [PMID:32273345]. These phenotypes place mtRPS18 alongside the small-subunit proteins PfmtRPS12 and PfmtRPS17 as a component whose loss compromises mitoribosome-dependent maintenance of the electron transport chain [PMID:32273345]. Beyond this single characterization [PMID:32273345], no further mechanistic detail on mtRPS18 — including its structural role within the small subunit, direct interaction partners, or the identity of transcripts it helps translate — has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Whether PF3D7_1211500 is a functional mitoribosomal component essential to the parasite was unknown; conditional knockdown established it as an essential small-subunit protein whose loss cripples mitochondrial energetics and pyrimidine synthesis.","evidence":"CRISPR/Cas9-based conditional knockdown with immuno-EM localization, drug sensitivity assays, and metabolite profiling in P. falciparum","pmids":["32273345"],"confidence":"Medium","gaps":["No in vitro reconstitution or structural validation of mtRPS18 within the small subunit","Direct RNA/protein interaction partners of mtRPS18 not identified","Phenotype shared with PfmtRPS12 and PfmtRPS17, so contributions specific to mtRPS18 are not separated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How mtRPS18 assembles into the mitoribosome and which specific translation events it supports remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of mtRPS18 in the small subunit","Mechanism linking mtRPS18 loss to membrane potential collapse not defined at the molecular level"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["mitochondrial small ribosomal subunit"],"partners":["PFMTRPS12","PFMTRPS17"],"other_free_text":["Knockdown collapses mitochondrial membrane potential and blocks pyrimidine biosynthesis [#0]","Loss confers hypersensitivity to Complex III (bc1), DHODH, and F1F0-ATP synthase inhibitors [#0]","Essential for P. falciparum viability [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32273345","id":"PMC_32273345","title":"Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32273345","citation_count":30,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S18","PfmtRPS18"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19635900","id":"PMC_19635900","title":"Quantitative determination of Plasmodium vivax gametocytes by real-time quantitative nucleic acid sequence-based amplification in clinical samples.","date":"2009","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/19635900","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PvS18"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3942,"output_tokens":508,"usd":0.009723,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5080,"output_tokens":1357,"usd":0.029663,"stage2_stop_reason":"end_turn"},"total_usd":0.039386,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_1211500 (mtRPS18/PfmtRPS18), a small subunit mitoribosomal protein, was verified by immuno-EM to localize within the mitochondrion and shown to be essential for parasite viability in P. falciparum; conditional CRISPR/Cas9-based knockdown demonstrated that loss of mtRPS18 (along with other small subunit proteins PfmtRPS12 and PfmtRPS17) compromises mitochondrial membrane potential and causes hypersensitivity to inhibitors of Complex III (bc1), DHODH, and F1F0-ATP synthase, and blocks pyrimidine biosynthesis by reducing the cellular pool of pyrimidine nucleotides.\",\n      \"method\": \"CRISPR/Cas9-based conditional knockdown, immuno-electron microscopy, drug sensitivity assays, metabolite profiling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined cellular and metabolic phenotypes plus immuno-EM localization, single lab, multiple orthogonal readouts but no in vitro reconstitution or structural validation of mtRPS18 specifically\",\n      \"pmids\": [\"32273345\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, mtRPS18 (PF3D7_1211500) is an essential component of the mitochondrial small ribosomal subunit that localizes to the inner mitochondrial membrane; its loss disrupts mitoribosome function, collapses mitochondrial membrane potential, blocks pyrimidine biosynthesis, and renders parasites hypersensitive to inhibitors targeting mitochondrial electron transport and the F1F0-ATP synthase.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In P. falciparum, mtRPS18 (PF3D7_1211500) is an essential small-subunit mitoribosomal protein required for mitochondrial function and parasite viability [#0]. Immuno-electron microscopy localizes mtRPS18 within the mitochondrion, and conditional CRISPR/Cas9 knockdown collapses the mitochondrial membrane potential, blocks pyrimidine biosynthesis by depleting cellular pyrimidine nucleotide pools, and renders parasites hypersensitive to inhibitors of Complex III (bc1), DHODH, and the F1F0-ATP synthase [#0]. These phenotypes place mtRPS18 alongside the small-subunit proteins PfmtRPS12 and PfmtRPS17 as a component whose loss compromises mitoribosome-dependent maintenance of the electron transport chain [#0]. Beyond this single characterization [#0], no further mechanistic detail on mtRPS18 — including its structural role within the small subunit, direct interaction partners, or the identity of transcripts it helps translate — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether PF3D7_1211500 is a functional mitoribosomal component essential to the parasite was unknown; conditional knockdown established it as an essential small-subunit protein whose loss cripples mitochondrial energetics and pyrimidine synthesis.\",\n      \"evidence\": \"CRISPR/Cas9-based conditional knockdown with immuno-EM localization, drug sensitivity assays, and metabolite profiling in P. falciparum\",\n      \"pmids\": [\"32273345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution or structural validation of mtRPS18 within the small subunit\",\n        \"Direct RNA/protein interaction partners of mtRPS18 not identified\",\n        \"Phenotype shared with PfmtRPS12 and PfmtRPS17, so contributions specific to mtRPS18 are not separated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How mtRPS18 assembles into the mitoribosome and which specific translation events it supports remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of mtRPS18 in the small subunit\",\n        \"Mechanism linking mtRPS18 loss to membrane potential collapse not defined at the molecular level\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005763\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032543\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006221\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"mitochondrial small ribosomal subunit\"],\n    \"partners\": [\"PfmtRPS12\", \"PfmtRPS17\"],\n    \"other_free_text\": [\n      \"Knockdown collapses mitochondrial membrane potential and blocks pyrimidine biosynthesis [#0]\",\n      \"Loss confers hypersensitivity to Complex III (bc1), DHODH, and F1F0-ATP synthase inhibitors [#0]\",\n      \"Essential for P. falciparum viability [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1211500","name":null,"product":"ribosomal protein S18, mitochondrial","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0610000","name":null,"product":"ribosomal protein S18, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1311600","name":null,"product":"ribosomal protein S18, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"mtRPS18","evaluation":null}