{"gene":"PF3D7_0318100","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2026,"finding":"P. falciparum STOML (PF3D7_0318100) localizes to distinct puncta at branching points and endings of the asexual blood-stage (ABS) mitochondrial network, as determined by epitope tagging of endogenous STOML.","method":"Endogenous epitope tagging and fluorescence microscopy","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with endogenous tag in P. falciparum, single lab, single method","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"Deletion of P. falciparum STOML causes a significant growth defect and slower asexual blood-stage development, while sexual-stage development remains unaffected, establishing a defined role in ABS parasite development.","method":"Genetic deletion (loss-of-function) with growth/development phenotypic readout","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype, single lab, multiple developmental stages assessed","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"STOML resides in a large protein complex, and pulldown experiments identified the zinc-dependent metalloprotease FtsH as a likely interaction partner. The predicted AlphaFold2 structure of STOML shows high similarity with bacterial HflK/C, which forms a vault-like structure around bacterial FtsH hexamers, suggesting a similar STOML–FtsH complex in P. falciparum mitochondria.","method":"Pulldown/co-immunoprecipitation mass spectrometry; AlphaFold2 structural prediction","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single pulldown experiment identifying interaction partner, structural similarity based on computational prediction only, no in vitro reconstitution or mutagenesis validation","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"Parasites lacking STOML were not more sensitive to respiratory chain-targeting drugs, rendering a function of STOML in respiratory chain assembly unlikely (negative finding).","method":"Drug sensitivity assay on STOML-knockout parasites","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method, negative result; informative for ruling out respiratory chain assembly role","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The P. berghei stomatin-like protein (ortholog of PF3D7_0318100) localizes to the parasite mitochondrion along with the other SPFH family members (PHB1, PHB2, PHBL). Attempts to delete the stomatin-like protein from the P. berghei genome were unsuccessful, suggesting it is essential for asexual blood-stage development in the murine malaria model.","method":"Fluorescence microscopy for localization; attempted gene deletion (essentiality inference from failed deletion)","journal":"Cell reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization by microscopy and essentiality inferred from failed KO attempts, single lab; essentiality is indirect","pmids":["29669282"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2003,"finding":"P. falciparum STOML (pfstom/PF3D7_0318100) protein is stage-specifically expressed in the trophozoite stage but not in the ring stage of erythrocytic development, and the recombinant C-terminal fragment was detected by Western blot.","method":"RT-PCR cloning, prokaryotic expression, Western blot with anti-recombinant-protein antibody","journal":"Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (Western blot), no functional follow-up","pmids":["12905716"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"FCC1/HN"}]}],"current_model":"PF3D7_0318100 (STOML) is a mitochondrion-localized SPFH-family protein in Plasmodium falciparum that is expressed in trophozoites, resides at distinct puncta on branching points and endings of the ABS mitochondrial network, is required for normal asexual blood-stage growth (but not sexual-stage development), and likely functions as part of a large complex with the zinc-dependent metalloprotease FtsH at these specific mitochondrial loci, analogous to the bacterial HflK/C–FtsH regulatory assembly."},"narrative":{"mechanistic_narrative":"PF3D7_0318100 (STOML) is a mitochondrion-localized SPFH-family stomatin-like protein of Plasmodium falciparum that functions in asexual blood-stage (ABS) development [PMID:41662436]. Endogenous epitope tagging places STOML at discrete puncta on branching points and endings of the ABS mitochondrial network rather than uniformly across the organelle [PMID:41662436], and stage-specific expression analysis shows it is present in trophozoites but not rings [PMID:12905716]. Genetic deletion of STOML causes a significant growth defect and slowed ABS development while leaving sexual-stage development intact, defining a role restricted to the asexual cycle [PMID:41662436]; knockout parasites are not sensitized to respiratory chain-targeting drugs, arguing against a role in respiratory chain assembly [PMID:41662436]. STOML resides in a large protein complex, with pulldown mass spectrometry identifying the zinc-dependent metalloprotease FtsH as a likely partner, and an AlphaFold2 model resembling bacterial HflK/C — which forms a vault-like assembly around FtsH hexamers — points to an analogous STOML–FtsH mitochondrial complex [PMID:41662436]. Beyond this complex membership and localization, the precise molecular activity of STOML has not been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing when STOML is expressed during the erythrocytic cycle was the first step toward defining its cellular context.","evidence":"RT-PCR cloning, prokaryotic expression and Western blot of a recombinant C-terminal fragment in P. falciparum FCC1/HN","pmids":["12905716"],"confidence":"Low","gaps":["No localization determined","No functional role assigned","Antigen detected only via recombinant fragment, not endogenous protein"],"attribution":[{"species":"Plasmodium falciparum","strain":"FCC1/HN"}]},{"year":2018,"claim":"Whether the stomatin-like protein resides in the mitochondrion and is required for blood-stage growth was addressed in a rodent malaria model.","evidence":"Fluorescence microscopy localization and attempted gene deletion in P. berghei","pmids":["29669282"],"confidence":"Low","gaps":["Essentiality inferred indirectly from failed deletion, not from a conditional system","Species is P. berghei, not the subject P. falciparum gene","Sub-mitochondrial localization not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"The sub-organellar position and stage-specific requirement of P. falciparum STOML were resolved, establishing a defined ABS-restricted role.","evidence":"Endogenous epitope tagging with fluorescence microscopy and genetic deletion with growth/developmental readout in P. falciparum","pmids":["41662436"],"confidence":"Medium","gaps":["Molecular reason for punctate localization at network branch points unknown","Mechanism linking loss of STOML to slowed asexual development not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Whether STOML acts alone or within a complex, and whether it participates in respiratory chain assembly, was tested to narrow its molecular function.","evidence":"Pulldown/co-IP mass spectrometry, AlphaFold2 structural prediction, and drug-sensitivity assay on STOML-knockout P. falciparum","pmids":["41662436"],"confidence":"Low","gaps":["FtsH interaction from a single pulldown without reciprocal validation, mutagenesis, or reconstitution","HflK/C-like architecture is computational prediction only, no experimental structure","Functional consequence of the STOML–FtsH complex undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical activity of STOML within the proposed FtsH complex and how it contributes to asexual blood-stage growth remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstrated enzymatic or scaffolding activity","Stoichiometry and architecture of the STOML–FtsH assembly not experimentally determined","Mechanistic basis of the growth defect not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Large STOML-containing complex including the zinc-dependent metalloprotease FtsH (likely, single pulldown) [#2]"],"partners":["FTSH (ZINC-DEPENDENT METALLOPROTEASE; LIKELY INTERACTION PARTNER) [#2]"],"other_free_text":["SPFH/stomatin-like family protein [#4]","Localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network [#0]","Stage-specifically expressed in trophozoites, not rings [#5]","Required for normal asexual blood-stage growth; sexual-stage development unaffected [#1]","P. berghei ortholog refractory to deletion, implying essentiality in that species [#4]","Knockout does not increase sensitivity to respiratory chain-targeting drugs, arguing against a respiratory chain assembly role [#3]","AlphaFold2 model resembles bacterial HflK/C, which vaults around FtsH hexamers [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29669282","id":"PMC_29669282","title":"An Unusual Prohibitin Regulates Malaria Parasite Mitochondrial Membrane Potential.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29669282","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["stomatin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41662436","id":"PMC_41662436","title":"Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41662436","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["STOML","stomatin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12905716","id":"PMC_12905716","title":"[Gene clone and its characteristics on band 7-like protein in Plasmodium falciparum FCC1/HN].","date":"2003","source":"Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae","url":"https://pubmed.ncbi.nlm.nih.gov/12905716","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["stomatin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4227,"output_tokens":1523,"usd":0.017763,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6533,"output_tokens":2124,"usd":0.042882,"stage2_stop_reason":"end_turn"},"total_usd":0.060645,"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\": 2026,\n      \"finding\": \"P. falciparum STOML (PF3D7_0318100) localizes to distinct puncta at branching points and endings of the asexual blood-stage (ABS) mitochondrial network, as determined by epitope tagging of endogenous STOML.\",\n      \"method\": \"Endogenous epitope tagging and fluorescence microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with endogenous tag in P. falciparum, single lab, single method\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Deletion of P. falciparum STOML causes a significant growth defect and slower asexual blood-stage development, while sexual-stage development remains unaffected, establishing a defined role in ABS parasite development.\",\n      \"method\": \"Genetic deletion (loss-of-function) with growth/development phenotypic readout\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype, single lab, multiple developmental stages assessed\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"STOML resides in a large protein complex, and pulldown experiments identified the zinc-dependent metalloprotease FtsH as a likely interaction partner. The predicted AlphaFold2 structure of STOML shows high similarity with bacterial HflK/C, which forms a vault-like structure around bacterial FtsH hexamers, suggesting a similar STOML–FtsH complex in P. falciparum mitochondria.\",\n      \"method\": \"Pulldown/co-immunoprecipitation mass spectrometry; AlphaFold2 structural prediction\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown experiment identifying interaction partner, structural similarity based on computational prediction only, no in vitro reconstitution or mutagenesis validation\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Parasites lacking STOML were not more sensitive to respiratory chain-targeting drugs, rendering a function of STOML in respiratory chain assembly unlikely (negative finding).\",\n      \"method\": \"Drug sensitivity assay on STOML-knockout parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method, negative result; informative for ruling out respiratory chain assembly role\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The P. berghei stomatin-like protein (ortholog of PF3D7_0318100) localizes to the parasite mitochondrion along with the other SPFH family members (PHB1, PHB2, PHBL). Attempts to delete the stomatin-like protein from the P. berghei genome were unsuccessful, suggesting it is essential for asexual blood-stage development in the murine malaria model.\",\n      \"method\": \"Fluorescence microscopy for localization; attempted gene deletion (essentiality inference from failed deletion)\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization by microscopy and essentiality inferred from failed KO attempts, single lab; essentiality is indirect\",\n      \"pmids\": [\"29669282\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"P. falciparum STOML (pfstom/PF3D7_0318100) protein is stage-specifically expressed in the trophozoite stage but not in the ring stage of erythrocytic development, and the recombinant C-terminal fragment was detected by Western blot.\",\n      \"method\": \"RT-PCR cloning, prokaryotic expression, Western blot with anti-recombinant-protein antibody\",\n      \"journal\": \"Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (Western blot), no functional follow-up\",\n      \"pmids\": [\"12905716\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"FCC1/HN\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0318100 (STOML) is a mitochondrion-localized SPFH-family protein in Plasmodium falciparum that is expressed in trophozoites, resides at distinct puncta on branching points and endings of the ABS mitochondrial network, is required for normal asexual blood-stage growth (but not sexual-stage development), and likely functions as part of a large complex with the zinc-dependent metalloprotease FtsH at these specific mitochondrial loci, analogous to the bacterial HflK/C–FtsH regulatory assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0318100 (STOML) is a mitochondrion-localized SPFH-family stomatin-like protein of Plasmodium falciparum that functions in asexual blood-stage (ABS) development [#1]. Endogenous epitope tagging places STOML at discrete puncta on branching points and endings of the ABS mitochondrial network rather than uniformly across the organelle [#0], and stage-specific expression analysis shows it is present in trophozoites but not rings [#5]. Genetic deletion of STOML causes a significant growth defect and slowed ABS development while leaving sexual-stage development intact, defining a role restricted to the asexual cycle [#1]; knockout parasites are not sensitized to respiratory chain-targeting drugs, arguing against a role in respiratory chain assembly [#3]. STOML resides in a large protein complex, with pulldown mass spectrometry identifying the zinc-dependent metalloprotease FtsH as a likely partner, and an AlphaFold2 model resembling bacterial HflK/C — which forms a vault-like assembly around FtsH hexamers — points to an analogous STOML–FtsH mitochondrial complex [#2]. Beyond this complex membership and localization, the precise molecular activity of STOML has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing when STOML is expressed during the erythrocytic cycle was the first step toward defining its cellular context.\",\n      \"evidence\": \"RT-PCR cloning, prokaryotic expression and Western blot of a recombinant C-terminal fragment in P. falciparum FCC1/HN\",\n      \"pmids\": [\"12905716\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No localization determined\", \"No functional role assigned\", \"Antigen detected only via recombinant fragment, not endogenous protein\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"FCC1/HN\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the stomatin-like protein resides in the mitochondrion and is required for blood-stage growth was addressed in a rodent malaria model.\",\n      \"evidence\": \"Fluorescence microscopy localization and attempted gene deletion in P. berghei\",\n      \"pmids\": [\"29669282\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Essentiality inferred indirectly from failed deletion, not from a conditional system\", \"Species is P. berghei, not the subject P. falciparum gene\", \"Sub-mitochondrial localization not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"The sub-organellar position and stage-specific requirement of P. falciparum STOML were resolved, establishing a defined ABS-restricted role.\",\n      \"evidence\": \"Endogenous epitope tagging with fluorescence microscopy and genetic deletion with growth/developmental readout in P. falciparum\",\n      \"pmids\": [\"41662436\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular reason for punctate localization at network branch points unknown\", \"Mechanism linking loss of STOML to slowed asexual development not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Whether STOML acts alone or within a complex, and whether it participates in respiratory chain assembly, was tested to narrow its molecular function.\",\n      \"evidence\": \"Pulldown/co-IP mass spectrometry, AlphaFold2 structural prediction, and drug-sensitivity assay on STOML-knockout P. falciparum\",\n      \"pmids\": [\"41662436\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"FtsH interaction from a single pulldown without reciprocal validation, mutagenesis, or reconstitution\", \"HflK/C-like architecture is computational prediction only, no experimental structure\", \"Functional consequence of the STOML–FtsH complex undetermined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of STOML within the proposed FtsH complex and how it contributes to asexual blood-stage growth remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No demonstrated enzymatic or scaffolding activity\", \"Stoichiometry and architecture of the STOML–FtsH assembly not experimentally determined\", \"Mechanistic basis of the growth defect not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Large STOML-containing complex including the zinc-dependent metalloprotease FtsH (likely, single pulldown) [#2]\"],\n    \"partners\": [\"FtsH (zinc-dependent metalloprotease; likely interaction partner) [#2]\"],\n    \"other_free_text\": [\n      \"SPFH/stomatin-like family protein [#4]\",\n      \"Localizes to distinct puncta at branching points and endings of the asexual blood-stage mitochondrial network [#0]\",\n      \"Stage-specifically expressed in trophozoites, not rings [#5]\",\n      \"Required for normal asexual blood-stage growth; sexual-stage development unaffected [#1]\",\n      \"P. berghei ortholog refractory to deletion, implying essentiality in that species [#4]\",\n      \"Knockout does not increase sensitivity to respiratory chain-targeting drugs, arguing against a respiratory chain assembly role [#3]\",\n      \"AlphaFold2 model resembles bacterial HflK/C, which vaults around FtsH hexamers [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0318100","name":null,"product":"stomatin-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0807100","name":null,"product":"stomatin-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0823700","name":null,"product":"stomatin-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"STOML","evaluation":null}