{"gene":"PF3D7_1470000","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2026,"finding":"ATG12 (PF3D7_1470000) functions as part of the ATG12–ATG5–ATG16 complex, which acts as an E3-like ligase to enable ATG8 membrane association (lipidation) in Plasmodium.","method":"Literature synthesis with mechanistic inference drawn from conserved conjugation system characterization in Plasmodium","journal":"Molecular microbiology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — review/synthesis paper, no direct experimental data on ATG12 itself reported in the abstract; single source with no primary experiment described","pmids":["42473197"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Transcription of ATG12 (PbATG12) in P. berghei is upregulated by chloroquine and 5-fluorouracil treatment, and downregulated by tunicamycin treatment, indicating that ATG12 expression is responsive to ER stress and drug-induced programmed cell death pathways.","method":"RT-qPCR (transcriptional analysis of autophagy-related genes in ex vivo P. berghei cultures treated with tunicamycin, 5-fluorouracil, and chloroquine)","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (transcriptional readout only), no protein-level or functional mechanistic data for ATG12 specifically","pmids":["38976068"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1470000 (ATG12) is proposed to function as part of the ATG12–ATG5–ATG16 E3-like ligase complex that facilitates ATG8 lipidation and membrane association in Plasmodium, but no direct primary experimental data on ATG12 itself (e.g., biochemical reconstitution, structural studies, or genetic loss-of-function) have been reported in the available literature; its transcripts are regulated by drug-induced stress in P. berghei."},"narrative":{"mechanistic_narrative":"PF3D7_1470000 (ATG12) is assigned to the ATG12–ATG5–ATG16 complex, which is described as an E3-like ligase that enables ATG8 membrane association (lipidation) in Plasmodium falciparum [PMID:42473197]. This assignment derives from literature synthesis and mechanistic inference from conserved conjugation systems rather than from direct experimental characterization of ATG12 itself; no biochemical reconstitution, structural study, or genetic loss-of-function analysis of PF3D7_1470000 is present in the available corpus [PMID:42473197]. In P. berghei, transcription of the ATG12 ortholog is upregulated by chloroquine and 5-fluorouracil and downregulated by tunicamycin, indicating its expression responds to drug-induced stress [PMID:38976068]. Beyond this complex membership assignment and transcriptional responsiveness, no direct mechanistic detail about PF3D7_1470000 has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"To ask whether ATG12 expression participates in stress and drug-induced cell death responses, its transcript levels were measured under distinct chemical stressors, establishing that ATG12 is transcriptionally regulated rather than constitutive.","evidence":"RT-qPCR of autophagy-related transcripts in ex vivo P. berghei cultures treated with tunicamycin, 5-fluorouracil, and chloroquine","pmids":["38976068"],"confidence":"Low","gaps":["Transcriptional readout only; no protein-level or functional data for ATG12","Does not establish whether ATG12 protein abundance or activity changes with the transcript","Shown in P. berghei; not tested in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"To place ATG12 in a pathway, it was assigned to the ATG12–ATG5–ATG16 E3-like ligase complex mediating ATG8 lipidation, framing its presumed molecular role in Plasmodium autophagy.","evidence":"Literature synthesis with mechanistic inference from conserved conjugation-system characterization in P. falciparum (review; no primary experiment on ATG12)","pmids":["42473197"],"confidence":"Low","gaps":["Assignment is inferred from conserved systems, not from direct experiments on PF3D7_1470000","No biochemical reconstitution of the ATG12–ATG5–ATG16 complex in Plasmodium","No demonstration that ATG12 itself is required for ATG8 lipidation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_1470000 physically conjugates to ATG5, forms the E3-like complex, and is functionally required for ATG8 lipidation and parasite autophagy remains untested by direct experiment.","evidence":"No structural, biochemical, or genetic loss-of-function study of ATG12 present in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown of ATG12 reported","No demonstration of ATG12–ATG5 conjugation in Plasmodium","No structural model or interaction mapping for ATG12"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["ATG12–ATG5–ATG16 E3-like ligase complex [#0]"],"partners":["ATG5 (INFERRED COMPLEX MEMBER) [#0]","ATG16 (INFERRED COMPLEX MEMBER) [#0]","ATG8 (LIPIDATION TARGET OF THE COMPLEX) [#0]"],"other_free_text":["Complex membership and E3-like ligase role are assigned by literature synthesis/inference from conserved conjugation systems, not by direct experiments on PF3D7_1470000 [#0].","In P. berghei, ATG12 transcript is upregulated by chloroquine and 5-fluorouracil and downregulated by tunicamycin [#1].","No biochemical, structural, or genetic loss-of-function data on PF3D7_1470000 itself are present in the corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36869438","id":"PMC_36869438","title":"Biological functions and structural biology of Plasmodium falciparum autophagy-related proteins: The under-explored options for novel antimalarial drug design.","date":"2023","source":"Chemical biology & drug design","url":"https://pubmed.ncbi.nlm.nih.gov/36869438","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfATG12"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38976068","id":"PMC_38976068","title":"Drug-induced ER stress leads to induction of programmed cell death pathways of the malaria parasite.","date":"2024","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/38976068","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbATG12"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42473197","id":"PMC_42473197","title":"Divergent Autophagy Pathways in Plasmodium: Mechanisms, Functions, and Therapeutic Potential.","date":"2026","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42473197","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG12"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4242,"output_tokens":642,"usd":0.011178,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5241,"output_tokens":1678,"usd":0.034077,"stage2_stop_reason":"end_turn"},"total_usd":0.045255,"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\": 2026,\n      \"finding\": \"ATG12 (PF3D7_1470000) functions as part of the ATG12–ATG5–ATG16 complex, which acts as an E3-like ligase to enable ATG8 membrane association (lipidation) in Plasmodium.\",\n      \"method\": \"Literature synthesis with mechanistic inference drawn from conserved conjugation system characterization in Plasmodium\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — review/synthesis paper, no direct experimental data on ATG12 itself reported in the abstract; single source with no primary experiment described\",\n      \"pmids\": [\"42473197\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Transcription of ATG12 (PbATG12) in P. berghei is upregulated by chloroquine and 5-fluorouracil treatment, and downregulated by tunicamycin treatment, indicating that ATG12 expression is responsive to ER stress and drug-induced programmed cell death pathways.\",\n      \"method\": \"RT-qPCR (transcriptional analysis of autophagy-related genes in ex vivo P. berghei cultures treated with tunicamycin, 5-fluorouracil, and chloroquine)\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (transcriptional readout only), no protein-level or functional mechanistic data for ATG12 specifically\",\n      \"pmids\": [\"38976068\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1470000 (ATG12) is proposed to function as part of the ATG12–ATG5–ATG16 E3-like ligase complex that facilitates ATG8 lipidation and membrane association in Plasmodium, but no direct primary experimental data on ATG12 itself (e.g., biochemical reconstitution, structural studies, or genetic loss-of-function) have been reported in the available literature; its transcripts are regulated by drug-induced stress in P. berghei.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1470000 (ATG12) is assigned to the ATG12–ATG5–ATG16 complex, which is described as an E3-like ligase that enables ATG8 membrane association (lipidation) in Plasmodium falciparum [#0]. This assignment derives from literature synthesis and mechanistic inference from conserved conjugation systems rather than from direct experimental characterization of ATG12 itself; no biochemical reconstitution, structural study, or genetic loss-of-function analysis of PF3D7_1470000 is present in the available corpus [#0]. In P. berghei, transcription of the ATG12 ortholog is upregulated by chloroquine and 5-fluorouracil and downregulated by tunicamycin, indicating its expression responds to drug-induced stress [#1]. Beyond this complex membership assignment and transcriptional responsiveness, no direct mechanistic detail about PF3D7_1470000 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"To ask whether ATG12 expression participates in stress and drug-induced cell death responses, its transcript levels were measured under distinct chemical stressors, establishing that ATG12 is transcriptionally regulated rather than constitutive.\",\n      \"evidence\": \"RT-qPCR of autophagy-related transcripts in ex vivo P. berghei cultures treated with tunicamycin, 5-fluorouracil, and chloroquine\",\n      \"pmids\": [\"38976068\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Transcriptional readout only; no protein-level or functional data for ATG12\",\n        \"Does not establish whether ATG12 protein abundance or activity changes with the transcript\",\n        \"Shown in P. berghei; not tested in P. falciparum\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"To place ATG12 in a pathway, it was assigned to the ATG12–ATG5–ATG16 E3-like ligase complex mediating ATG8 lipidation, framing its presumed molecular role in Plasmodium autophagy.\",\n      \"evidence\": \"Literature synthesis with mechanistic inference from conserved conjugation-system characterization in P. falciparum (review; no primary experiment on ATG12)\",\n      \"pmids\": [\"42473197\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Assignment is inferred from conserved systems, not from direct experiments on PF3D7_1470000\",\n        \"No biochemical reconstitution of the ATG12–ATG5–ATG16 complex in Plasmodium\",\n        \"No demonstration that ATG12 itself is required for ATG8 lipidation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1470000 physically conjugates to ATG5, forms the E3-like complex, and is functionally required for ATG8 lipidation and parasite autophagy remains untested by direct experiment.\",\n      \"evidence\": \"No structural, biochemical, or genetic loss-of-function study of ATG12 present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown of ATG12 reported\",\n        \"No demonstration of ATG12–ATG5 conjugation in Plasmodium\",\n        \"No structural model or interaction mapping for ATG12\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019776\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006914\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"ATG12–ATG5–ATG16 E3-like ligase complex [#0]\"\n    ],\n    \"partners\": [\n      \"ATG5 (inferred complex member) [#0]\",\n      \"ATG16 (inferred complex member) [#0]\",\n      \"ATG8 (lipidation target of the complex) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Complex membership and E3-like ligase role are assigned by literature synthesis/inference from conserved conjugation systems, not by direct experiments on PF3D7_1470000 [#0].\",\n      \"In P. berghei, ATG12 transcript is upregulated by chloroquine and 5-fluorouracil and downregulated by tunicamycin [#1].\",\n      \"No biochemical, structural, or genetic loss-of-function data on PF3D7_1470000 itself are present in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1470000","name":null,"product":"autophagy-related protein 12, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1333200","name":null,"product":"autophagy-related protein 12, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1211000","name":null,"product":"autophagy-related protein 12, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATG12","evaluation":null}