{"gene":"PF3D7_0823700","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2004,"finding":"Comparative sequence analysis identified a TOM7 ortholog in Plasmodium falciparum, suggesting it is a conserved core subunit of the translocase of the outer mitochondrial membrane (TOM complex), alongside Tom40 and Tom22, present across diverse eukaryotes.","method":"Comparative sequence analysis / bioinformatics identification of ortholog","journal":"Molecular biology and evolution","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence analysis only, no direct functional experiment performed in Plasmodium","pmids":["15155803"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Native electrophoresis (complexomics) data showed that PfTOM7 (PF3D7_0823700) co-migrates with both the TOM complex and the ER membrane complex (EMC) in P. falciparum, suggesting PfTOM7 may serve as a tether bridging the ER and mitochondrion in a manner analogous to TOM5 in yeast, which is absent from the Plasmodium genome.","method":"Native gel electrophoresis / complexomics co-migration analysis; AlphaFold structural prediction and multiple sequence alignment","journal":"Nature communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-migration observation from native electrophoresis without direct functional validation of the tethering role; structural similarity is predicted, not experimentally confirmed","pmids":["39747010"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfTOM7 (PF3D7_0823700) is a conserved subunit of the translocase of the outer mitochondrial membrane (TOM complex) in Plasmodium falciparum; complexomics data additionally suggest it co-migrates with the ER membrane complex (EMC), raising the possibility that it acts as an ER-mitochondrion tether in place of the yeast TOM5, but no direct functional experiment has yet confirmed this role."},"narrative":{"mechanistic_narrative":"PF3D7_0823700 (TOM7) is identified as a conserved core subunit of the translocase of the outer mitochondrial membrane (TOM complex) in Plasmodium falciparum, recognized by comparative sequence analysis as an ortholog present alongside Tom40 and Tom22 across diverse eukaryotes [PMID:15155803]. Native complexomics places PF3D7_0823700 in co-migration with both the TOM complex and the ER membrane complex (EMC), raising the possibility that it bridges the ER and mitochondrion analogously to yeast TOM5, which is absent from the Plasmodium genome [PMID:39747010]. Beyond its assignment as a TOM complex subunit and this co-migration observation, no direct functional characterization of PF3D7_0823700 has been performed in the available corpus.","teleology":[{"year":2004,"claim":"Before this work it was unclear whether Plasmodium encodes the small core TOM subunits; identifying a TOM7 ortholog established PF3D7_0823700 as a candidate conserved component of the mitochondrial protein import machinery.","evidence":"comparative sequence analysis / bioinformatic ortholog identification in P. falciparum","pmids":["15155803"],"confidence":"Low","gaps":["computational assignment only, with no functional experiment in Plasmodium","membership in an assembled TOM complex not demonstrated","no localization data for the protein itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To move beyond sequence prediction, native complexomics tested which complexes PF3D7_0823700 associates with, showing it co-migrates with both the TOM complex and the EMC and raising the hypothesis that it serves as an ER-mitochondrion tether in place of the absent yeast TOM5.","evidence":"native gel electrophoresis / complexomics co-migration with AlphaFold prediction and multiple sequence alignment in P. falciparum","pmids":["39747010"],"confidence":"Low","gaps":["single co-migration observation without direct functional validation of a tethering role","structural similarity to TOM5 is predicted, not experimentally confirmed","no genetic or biochemical test of ER-mitochondrion contact function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0823700 is functionally required for mitochondrial protein import and whether it physically tethers the ER to the mitochondrion remain untested.","evidence":"no direct functional or genetic experiment in the available corpus","pmids":[],"confidence":"Low","gaps":["no knockout/knockdown phenotype established","no reconstitution or interaction assay confirming the proposed EMC-mitochondrion bridge","import substrate dependence on PF3D7_0823700 not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TOM complex (translocase of the outer mitochondrial membrane)","ER membrane complex (EMC) — co-migration only"],"partners":[],"other_free_text":["Identified as a conserved TOM7 ortholog in P. falciparum by comparative sequence analysis [#0].","Co-migrates with both the TOM complex and the EMC by native complexomics, prompting a proposed ER-mitochondrion tethering role analogous to yeast TOM5 (absent in Plasmodium); tether function is not experimentally confirmed [#1].","No direct functional characterization of PF3D7_0823700 exists in the corpus beyond complex membership and co-migration."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15155803","id":"PMC_15155803","title":"Tom22', an 8-kDa trans-site receptor in plants and protozoans, is a conserved feature of the TOM complex that appeared early in the evolution of eukaryotes.","date":"2004","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/15155803","citation_count":85,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TOM7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39747010","id":"","title":"Comparative 3D ultrastructure of Plasmodium falciparum gametocytes.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39747010","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TOM7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36624300","id":"","title":"Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36624300","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TOM7"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5733,"output_tokens":624,"usd":0.013279,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5242,"output_tokens":1505,"usd":0.031918,"stage2_stop_reason":"end_turn"},"total_usd":0.045197,"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\": 2004,\n      \"finding\": \"Comparative sequence analysis identified a TOM7 ortholog in Plasmodium falciparum, suggesting it is a conserved core subunit of the translocase of the outer mitochondrial membrane (TOM complex), alongside Tom40 and Tom22, present across diverse eukaryotes.\",\n      \"method\": \"Comparative sequence analysis / bioinformatics identification of ortholog\",\n      \"journal\": \"Molecular biology and evolution\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence analysis only, no direct functional experiment performed in Plasmodium\",\n      \"pmids\": [\"15155803\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Native electrophoresis (complexomics) data showed that PfTOM7 (PF3D7_0823700) co-migrates with both the TOM complex and the ER membrane complex (EMC) in P. falciparum, suggesting PfTOM7 may serve as a tether bridging the ER and mitochondrion in a manner analogous to TOM5 in yeast, which is absent from the Plasmodium genome.\",\n      \"method\": \"Native gel electrophoresis / complexomics co-migration analysis; AlphaFold structural prediction and multiple sequence alignment\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-migration observation from native electrophoresis without direct functional validation of the tethering role; structural similarity is predicted, not experimentally confirmed\",\n      \"pmids\": [\"39747010\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfTOM7 (PF3D7_0823700) is a conserved subunit of the translocase of the outer mitochondrial membrane (TOM complex) in Plasmodium falciparum; complexomics data additionally suggest it co-migrates with the ER membrane complex (EMC), raising the possibility that it acts as an ER-mitochondrion tether in place of the yeast TOM5, but no direct functional experiment has yet confirmed this role.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0823700 (TOM7) is identified as a conserved core subunit of the translocase of the outer mitochondrial membrane (TOM complex) in Plasmodium falciparum, recognized by comparative sequence analysis as an ortholog present alongside Tom40 and Tom22 across diverse eukaryotes [#0]. Native complexomics places PF3D7_0823700 in co-migration with both the TOM complex and the ER membrane complex (EMC), raising the possibility that it bridges the ER and mitochondrion analogously to yeast TOM5, which is absent from the Plasmodium genome [#1]. Beyond its assignment as a TOM complex subunit and this co-migration observation, no direct functional characterization of PF3D7_0823700 has been performed in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Before this work it was unclear whether Plasmodium encodes the small core TOM subunits; identifying a TOM7 ortholog established PF3D7_0823700 as a candidate conserved component of the mitochondrial protein import machinery.\",\n      \"evidence\": \"comparative sequence analysis / bioinformatic ortholog identification in P. falciparum\",\n      \"pmids\": [\"15155803\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"computational assignment only, with no functional experiment in Plasmodium\",\n        \"membership in an assembled TOM complex not demonstrated\",\n        \"no localization data for the protein itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To move beyond sequence prediction, native complexomics tested which complexes PF3D7_0823700 associates with, showing it co-migrates with both the TOM complex and the EMC and raising the hypothesis that it serves as an ER-mitochondrion tether in place of the absent yeast TOM5.\",\n      \"evidence\": \"native gel electrophoresis / complexomics co-migration with AlphaFold prediction and multiple sequence alignment in P. falciparum\",\n      \"pmids\": [\"39747010\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"single co-migration observation without direct functional validation of a tethering role\",\n        \"structural similarity to TOM5 is predicted, not experimentally confirmed\",\n        \"no genetic or biochemical test of ER-mitochondrion contact function\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0823700 is functionally required for mitochondrial protein import and whether it physically tethers the ER to the mitochondrion remain untested.\",\n      \"evidence\": \"no direct functional or genetic experiment in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no knockout/knockdown phenotype established\",\n        \"no reconstitution or interaction assay confirming the proposed EMC-mitochondrion bridge\",\n        \"import substrate dependence on PF3D7_0823700 not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"mitochondrial outer membrane translocase (TOM) complex\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"TOM complex (translocase of the outer mitochondrial membrane)\",\n      \"ER membrane complex (EMC) — co-migration only\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Identified as a conserved TOM7 ortholog in P. falciparum by comparative sequence analysis [#0].\",\n      \"Co-migrates with both the TOM complex and the EMC by native complexomics, prompting a proposed ER-mitochondrion tethering role analogous to yeast TOM5 (absent in Plasmodium); tether function is not experimentally confirmed [#1].\",\n      \"No direct functional characterization of PF3D7_0823700 exists in the corpus beyond complex membership and co-migration.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0823700","name":null,"product":"mitochondrial import receptor subunit TOM7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0706900","name":null,"product":"mitochondrial import receptor subunit TOM7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1317700","name":null,"product":"mitochondrial import receptor subunit TOM7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"TOM7","evaluation":null}