{"gene":"PF3D7_0618600","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2013,"finding":"ROM10 is dispensable for asexual blood stage development in P. berghei; gene deletion of ROM10 produced parasites with no major phenotypic defects in blood stages, mosquito stages, or liver stages, indicating ROM10 is not essential for life cycle progression under standard laboratory conditions.","method":"Systematic gene deletion (reverse genetics / loss-of-function) in P. berghei with phenotypic assessment across life cycle stages","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gene knockout with defined phenotypic readouts across multiple life cycle stages, single lab but multiple stage assessments","pmids":["23490234"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"N-terminal 3xHA tagging of ROM10 (PF3D7_0618600) was deleterious in P. falciparum, preventing recovery of drug-resistant parasites; successful SHIFTiKO knockout was achieved only with constructs lacking the N-terminal tag, establishing that N-terminal modification impairs ROM10 function.","method":"SHIFTiKO (frameshift-based inducible knockout) with DiCre-lox system; transfection with and without N-terminal 3xHA tag constructs in P. falciparum","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single indirect observation (failure to recover parasites with N-terminal tag), no direct functional mechanistic follow-up","pmids":["39739757"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"In P. berghei gametocytes, ROM10 mRNA (PBANKA_111780) is associated with the translational repressors DOZI and CITH, placing it in the maternal repressome and indicating its transcript is stored in a translationally repressed state for use during post-fertilization development.","method":"RNA immunoprecipitation coupled to microarray analysis (RIP-Chip) using DOZI and CITH as bait proteins","journal":"Genome biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/RIP experiment identifying transcript association, no direct functional validation of ROM10 protein activity shown","pmids":["25418785"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"ROM10 (PF3D7_0618600) is a rhomboid intramembrane protease family member that is dispensable for blood stage, mosquito stage, and liver stage development in P. berghei, whose mRNA is stored in a translationally repressed state in gametocytes, and whose N-terminal region appears functionally important in P. falciparum; no specific substrate or catalytic mechanism has been experimentally established for ROM10 itself."},"narrative":{"mechanistic_narrative":"ROM10 (PF3D7_0618600) is a rhomboid intramembrane protease family member whose loss-of-function studies indicate it is dispensable for parasite life cycle progression: systematic gene deletion in P. berghei produced parasites with no major defects across blood, mosquito, and liver stages under standard laboratory conditions [PMID:23490234]. In P. falciparum, N-terminal 3xHA tagging of ROM10 is deleterious and blocks recovery of drug-resistant parasites, so that inducible knockout was achievable only with constructs lacking the N-terminal tag, establishing that the N-terminal region is functionally important [PMID:39739757]. In P. berghei gametocytes, the ROM10 transcript associates with the translational repressors DOZI and CITH, placing it within the maternal repressome and indicating the mRNA is stored in a translationally repressed state for post-fertilization use [PMID:25418785]. Beyond these observations, no substrate, catalytic activity, subcellular localization, or interacting protease complex has been characterized for ROM10 itself in the available corpus.","teleology":[{"year":2013,"claim":"To ask whether ROM10 is required for parasite survival, its gene was deleted and the resulting parasites were assessed across the life cycle, establishing that ROM10 is not essential under laboratory conditions.","evidence":"Systematic reverse-genetics gene deletion with phenotypic assessment across blood, mosquito, and liver stages in P. berghei","pmids":["23490234"],"confidence":"Medium","gaps":["Dispensability under standard conditions does not exclude a stage-specific or stress-conditional role","No substrate, catalytic activity, or localization determined","Findings in P. berghei may not transfer to P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"To understand how ROM10 expression is timed, its transcript was tested for association with maternal repressors, showing it is stored translationally repressed in gametocytes for later developmental deployment.","evidence":"RIP-Chip using DOZI and CITH as bait in P. berghei gametocytes","pmids":["25418785"],"confidence":"Low","gaps":["Single RIP experiment without functional validation of ROM10 protein activity","Timing and trigger of translational de-repression not defined","Does not establish what ROM10 protein does post-fertilization"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"To probe the functional importance of ROM10's N-terminus, tagging and inducible knockout were attempted, revealing that N-terminal modification impairs ROM10 function.","evidence":"SHIFTiKO inducible knockout with DiCre-lox and N-terminal 3xHA tag constructs in P. falciparum; failure to recover parasites carrying the N-terminal tag","pmids":["39739757"],"confidence":"Low","gaps":["Inference rests on failure to recover tagged parasites, an indirect readout without mechanistic follow-up","Why the N-terminus is required (folding, localization, catalysis) is unresolved","No direct assay of ROM10 protease activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The catalytic substrate, protease activity, subcellular localization, and physiological role of ROM10 itself remain undefined.","evidence":"No discovery in the corpus assays ROM10 substrate cleavage, catalytic mechanism, or localization","pmids":[],"confidence":"Low","gaps":["No substrate identified for ROM10","No demonstration of intramembrane protease activity for ROM10 specifically","No localization or interacting-complex data for ROM10"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["DOZI (ROM10 TRANSCRIPT ASSOCIATED IN MATERNAL REPRESSOME) [#2]","CITH (ROM10 TRANSCRIPT ASSOCIATED IN MATERNAL REPRESSOME) [#2]"],"other_free_text":["ROM10 (PF3D7_0618600) is annotated as a rhomboid intramembrane protease family member; no protease activity or substrate has been experimentally established for ROM10 itself in the corpus.","Gene deletion in P. berghei shows ROM10 is dispensable for blood, mosquito, and liver stage development [#0].","ROM10 mRNA is stored translationally repressed via association with DOZI/CITH in P. berghei gametocytes [#2].","N-terminal 3xHA tagging is deleterious in P. falciparum, indicating the N-terminal region is functionally important [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"17040128","id":"PMC_17040128","title":"Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria.","date":"2006","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/17040128","citation_count":180,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23490234","id":"PMC_23490234","title":"Loss-of-function analyses defines vital and redundant functions of the Plasmodium rhomboid protease family.","date":"2013","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23490234","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ROM10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39739757","id":"","title":"A scaleable inducible knockout system for studying essential gene function in the malaria parasite.","date":"2025","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/39739757","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ROM10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28107409","id":"","title":"Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.","date":"2017","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/28107409","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ROM10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25418785","id":"","title":"Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte.","date":"2014","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/25418785","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ROM10"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6594,"output_tokens":878,"usd":0.016476,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5597,"output_tokens":1821,"usd":0.036755,"stage2_stop_reason":"end_turn"},"total_usd":0.053231,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"ROM10 is dispensable for asexual blood stage development in P. berghei; gene deletion of ROM10 produced parasites with no major phenotypic defects in blood stages, mosquito stages, or liver stages, indicating ROM10 is not essential for life cycle progression under standard laboratory conditions.\",\n      \"method\": \"Systematic gene deletion (reverse genetics / loss-of-function) in P. berghei with phenotypic assessment across life cycle stages\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gene knockout with defined phenotypic readouts across multiple life cycle stages, single lab but multiple stage assessments\",\n      \"pmids\": [\"23490234\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"N-terminal 3xHA tagging of ROM10 (PF3D7_0618600) was deleterious in P. falciparum, preventing recovery of drug-resistant parasites; successful SHIFTiKO knockout was achieved only with constructs lacking the N-terminal tag, establishing that N-terminal modification impairs ROM10 function.\",\n      \"method\": \"SHIFTiKO (frameshift-based inducible knockout) with DiCre-lox system; transfection with and without N-terminal 3xHA tag constructs in P. falciparum\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single indirect observation (failure to recover parasites with N-terminal tag), no direct functional mechanistic follow-up\",\n      \"pmids\": [\"39739757\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In P. berghei gametocytes, ROM10 mRNA (PBANKA_111780) is associated with the translational repressors DOZI and CITH, placing it in the maternal repressome and indicating its transcript is stored in a translationally repressed state for use during post-fertilization development.\",\n      \"method\": \"RNA immunoprecipitation coupled to microarray analysis (RIP-Chip) using DOZI and CITH as bait proteins\",\n      \"journal\": \"Genome biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/RIP experiment identifying transcript association, no direct functional validation of ROM10 protein activity shown\",\n      \"pmids\": [\"25418785\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ROM10 (PF3D7_0618600) is a rhomboid intramembrane protease family member that is dispensable for blood stage, mosquito stage, and liver stage development in P. berghei, whose mRNA is stored in a translationally repressed state in gametocytes, and whose N-terminal region appears functionally important in P. falciparum; no specific substrate or catalytic mechanism has been experimentally established for ROM10 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ROM10 (PF3D7_0618600) is a rhomboid intramembrane protease family member whose loss-of-function studies indicate it is dispensable for parasite life cycle progression: systematic gene deletion in P. berghei produced parasites with no major defects across blood, mosquito, and liver stages under standard laboratory conditions [#0]. In P. falciparum, N-terminal 3xHA tagging of ROM10 is deleterious and blocks recovery of drug-resistant parasites, so that inducible knockout was achievable only with constructs lacking the N-terminal tag, establishing that the N-terminal region is functionally important [#1]. In P. berghei gametocytes, the ROM10 transcript associates with the translational repressors DOZI and CITH, placing it within the maternal repressome and indicating the mRNA is stored in a translationally repressed state for post-fertilization use [#2]. Beyond these observations, no substrate, catalytic activity, subcellular localization, or interacting protease complex has been characterized for ROM10 itself in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"To ask whether ROM10 is required for parasite survival, its gene was deleted and the resulting parasites were assessed across the life cycle, establishing that ROM10 is not essential under laboratory conditions.\",\n      \"evidence\": \"Systematic reverse-genetics gene deletion with phenotypic assessment across blood, mosquito, and liver stages in P. berghei\",\n      \"pmids\": [\"23490234\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Dispensability under standard conditions does not exclude a stage-specific or stress-conditional role\",\n        \"No substrate, catalytic activity, or localization determined\",\n        \"Findings in P. berghei may not transfer to P. falciparum\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To understand how ROM10 expression is timed, its transcript was tested for association with maternal repressors, showing it is stored translationally repressed in gametocytes for later developmental deployment.\",\n      \"evidence\": \"RIP-Chip using DOZI and CITH as bait in P. berghei gametocytes\",\n      \"pmids\": [\"25418785\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single RIP experiment without functional validation of ROM10 protein activity\",\n        \"Timing and trigger of translational de-repression not defined\",\n        \"Does not establish what ROM10 protein does post-fertilization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To probe the functional importance of ROM10's N-terminus, tagging and inducible knockout were attempted, revealing that N-terminal modification impairs ROM10 function.\",\n      \"evidence\": \"SHIFTiKO inducible knockout with DiCre-lox and N-terminal 3xHA tag constructs in P. falciparum; failure to recover parasites carrying the N-terminal tag\",\n      \"pmids\": [\"39739757\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Inference rests on failure to recover tagged parasites, an indirect readout without mechanistic follow-up\",\n        \"Why the N-terminus is required (folding, localization, catalysis) is unresolved\",\n        \"No direct assay of ROM10 protease activity\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic substrate, protease activity, subcellular localization, and physiological role of ROM10 itself remain undefined.\",\n      \"evidence\": \"No discovery in the corpus assays ROM10 substrate cleavage, catalytic mechanism, or localization\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No substrate identified for ROM10\",\n        \"No demonstration of intramembrane protease activity for ROM10 specifically\",\n        \"No localization or interacting-complex data for ROM10\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"DOZI (ROM10 transcript associated in maternal repressome) [#2]\", \"CITH (ROM10 transcript associated in maternal repressome) [#2]\"],\n    \"other_free_text\": [\n      \"ROM10 (PF3D7_0618600) is annotated as a rhomboid intramembrane protease family member; no protease activity or substrate has been experimentally established for ROM10 itself in the corpus.\",\n      \"Gene deletion in P. berghei shows ROM10 is dispensable for blood, mosquito, and liver stage development [#0].\",\n      \"ROM10 mRNA is stored translationally repressed via association with DOZI/CITH in P. berghei gametocytes [#2].\",\n      \"N-terminal 3xHA tagging is deleterious in P. falciparum, indicating the N-terminal region is functionally important [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0618600","name":null,"product":"rhomboid protease ROM10","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1117800","name":null,"product":"rhomboid protease ROM10","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1131800","name":null,"product":"rhomboid protease ROM10, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ROM10","evaluation":null}