{"gene":"PF3D7_0709300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2022,"finding":"PF3D7_0709300 (PfMed14) was identified with high confidence as a component of the physical Mediator complex in P. falciparum, consistent with its predicted role as the scaffold subunit stabilizing the head, middle, and tail modules. It was detected by coimmunoprecipitation of PfMed31 followed by mass spectrometry.","method":"Coimmunoprecipitation of PfMed31 coupled with mass spectrometry","journal":"ACS omega","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP/MS detected PfMed14 with high confidence in a single lab study; no mutagenesis or functional validation of PfMed14 itself was performed","pmids":["35557691"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"PF3D7_0709300 (PfMed14, annotated as a mediator of RNA polymerase II transcription subunit) was identified as an interaction partner of the histone methyltransferase PfSET10 in P. falciparum blood-stage nuclei, placing it within a broader chromatin modulation and transcriptional regulation network.","method":"TurboID proximity labeling coupled with mass spectrometry","journal":"mSphere","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling (TurboID-MS) in a single study; no direct functional validation of PfMed14 itself was performed beyond detection as an interactor","pmids":["39445823"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"Comparative genomics predicted P. falciparum to encode a Med14 homolog as part of a conserved Mediator complex framework; however, this was a computational prediction without experimental validation of the P. falciparum protein itself.","method":"Comparative genomics / bioinformatics","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation of the P. falciparum Med14 protein","pmids":["18515835"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0709300 (PfMed14) is physically present in the P. falciparum Mediator complex, detected by coimmunoprecipitation/mass spectrometry of the conserved subunit PfMed31, and consistent with its predicted scaffold role bridging the head, middle, and tail Mediator modules; it also appears in proximity to the histone methyltransferase PfSET10's nuclear interaction network, but no direct enzymatic activity, structural data, or loss-of-function phenotype has been experimentally established for PfMed14 itself."},"narrative":{"mechanistic_narrative":"PF3D7_0709300 (PfMed14) is a component of the Plasmodium falciparum Mediator complex, identified with high confidence by coimmunoprecipitation of the conserved subunit PfMed31 followed by mass spectrometry, consistent with a predicted scaffold role stabilizing the head, middle, and tail Mediator modules [PMID:35557691]. Beyond its physical membership in this complex, no direct enzymatic activity, structural data, or loss-of-function phenotype has been experimentally established for PfMed14 itself in the available corpus. A proximity-labeling study additionally detected PfMed14 within the nuclear interaction network of the histone methyltransferase PfSET10, placing it near chromatin-modulation machinery, but this reflects co-detection rather than a validated direct interaction or defined function for PfMed14 [PMID:39445823].","teleology":[{"year":2008,"claim":"Before any experimental work, it was unknown whether P. falciparum encoded a Mediator scaffold subunit; comparative genomics predicted a Med14 homolog, establishing a candidate gene to test.","evidence":"Comparative genomics / bioinformatics prediction of a conserved Mediator framework","pmids":["18515835"],"confidence":"Low","gaps":["Computational prediction only; the P. falciparum protein was not experimentally detected or validated","No evidence of expression, assembly, or function","Predicted module-bridging role untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To test whether the predicted subunit is actually assembled into a Mediator complex, reciprocal proteomics from a conserved subunit was needed; Co-IP of PfMed31 with mass spectrometry detected PfMed14 as a bona fide complex member, confirming physical presence in the P. falciparum Mediator.","evidence":"Coimmunoprecipitation of PfMed31 coupled with mass spectrometry","pmids":["35557691"],"confidence":"Medium","gaps":["No mutagenesis or functional validation of PfMed14 itself","Predicted scaffold/module-bridging role inferred, not structurally demonstrated","No loss-of-function phenotype established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"To place PfMed14 in a broader regulatory context, proximity labeling from a chromatin modifier was used; PfMed14 was detected in the nuclear interaction network of the histone methyltransferase PfSET10, linking it to chromatin-modulation and transcriptional regulation.","evidence":"TurboID proximity labeling coupled with mass spectrometry in blood-stage nuclei","pmids":["39445823"],"confidence":"Low","gaps":["Proximity detection only; no direct or reciprocal validation of a PfMed14–PfSET10 interaction","Functional consequence of the association unknown","Cannot distinguish direct contact from shared nuclear compartment"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what PfMed14 does mechanistically beyond complex membership: no enzymatic activity, structure, essentiality, or loss-of-function phenotype for PfMed14 itself has been established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional knockdown/knockout phenotype for PfMed14","No structural model of PfMed14 within the P. falciparum Mediator","No demonstration of a scaffold/module-bridging function specific to PfMed14"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mediator complex (P. falciparum)"],"partners":["PFMED31 (CO-IP/MS)","PFSET10 (PROXIMITY LABELING)"],"other_free_text":["Detected as a physical Mediator complex member by reciprocal Co-IP/MS of PfMed31 [#0].","Predicted scaffold subunit bridging head, middle, and tail Mediator modules, inferred from homology rather than direct structural evidence [#0, #2].","No enzymatic activity, structural data, or loss-of-function phenotype established for PfMed14 itself in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"4971014","id":"PMC_4971014","title":"DNA, RNA , and protein synthesis in erythrocytic forms of Plasmodium knowlesi.","date":"1968","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/4971014","citation_count":56,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31877193","id":"PMC_31877193","title":"Protein-RNA interactions important for Plasmodium transmission.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/31877193","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35557691","id":"","title":"Mediator Complex of the Malaria Parasite Plasmodium falciparum Associates with Evolutionarily Novel Subunits.","date":"2022","source":"ACS omega","url":"https://pubmed.ncbi.nlm.nih.gov/35557691","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MED14"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39445823","id":"","title":"The Plasmodium falciparum histone methyltransferase SET10 participates in a chromatin modulation network crucial for intraerythrocytic development.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/39445823","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MED14"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18515835","id":"","title":"Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex.","date":"2008","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/18515835","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MED14"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5865,"output_tokens":873,"usd":0.015345,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5552,"output_tokens":1810,"usd":0.036505,"stage2_stop_reason":"end_turn"},"total_usd":0.05185,"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\": 2022,\n      \"finding\": \"PF3D7_0709300 (PfMed14) was identified with high confidence as a component of the physical Mediator complex in P. falciparum, consistent with its predicted role as the scaffold subunit stabilizing the head, middle, and tail modules. It was detected by coimmunoprecipitation of PfMed31 followed by mass spectrometry.\",\n      \"method\": \"Coimmunoprecipitation of PfMed31 coupled with mass spectrometry\",\n      \"journal\": \"ACS omega\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP/MS detected PfMed14 with high confidence in a single lab study; no mutagenesis or functional validation of PfMed14 itself was performed\",\n      \"pmids\": [\"35557691\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PF3D7_0709300 (PfMed14, annotated as a mediator of RNA polymerase II transcription subunit) was identified as an interaction partner of the histone methyltransferase PfSET10 in P. falciparum blood-stage nuclei, placing it within a broader chromatin modulation and transcriptional regulation network.\",\n      \"method\": \"TurboID proximity labeling coupled with mass spectrometry\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling (TurboID-MS) in a single study; no direct functional validation of PfMed14 itself was performed beyond detection as an interactor\",\n      \"pmids\": [\"39445823\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Comparative genomics predicted P. falciparum to encode a Med14 homolog as part of a conserved Mediator complex framework; however, this was a computational prediction without experimental validation of the P. falciparum protein itself.\",\n      \"method\": \"Comparative genomics / bioinformatics\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation of the P. falciparum Med14 protein\",\n      \"pmids\": [\"18515835\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0709300 (PfMed14) is physically present in the P. falciparum Mediator complex, detected by coimmunoprecipitation/mass spectrometry of the conserved subunit PfMed31, and consistent with its predicted scaffold role bridging the head, middle, and tail Mediator modules; it also appears in proximity to the histone methyltransferase PfSET10's nuclear interaction network, but no direct enzymatic activity, structural data, or loss-of-function phenotype has been experimentally established for PfMed14 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0709300 (PfMed14) is a component of the Plasmodium falciparum Mediator complex, identified with high confidence by coimmunoprecipitation of the conserved subunit PfMed31 followed by mass spectrometry, consistent with a predicted scaffold role stabilizing the head, middle, and tail Mediator modules [#0]. Beyond its physical membership in this complex, no direct enzymatic activity, structural data, or loss-of-function phenotype has been experimentally established for PfMed14 itself in the available corpus. A proximity-labeling study additionally detected PfMed14 within the nuclear interaction network of the histone methyltransferase PfSET10, placing it near chromatin-modulation machinery, but this reflects co-detection rather than a validated direct interaction or defined function for PfMed14 [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Before any experimental work, it was unknown whether P. falciparum encoded a Mediator scaffold subunit; comparative genomics predicted a Med14 homolog, establishing a candidate gene to test.\",\n      \"evidence\": \"Comparative genomics / bioinformatics prediction of a conserved Mediator framework\",\n      \"pmids\": [\"18515835\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only; the P. falciparum protein was not experimentally detected or validated\",\n        \"No evidence of expression, assembly, or function\",\n        \"Predicted module-bridging role untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To test whether the predicted subunit is actually assembled into a Mediator complex, reciprocal proteomics from a conserved subunit was needed; Co-IP of PfMed31 with mass spectrometry detected PfMed14 as a bona fide complex member, confirming physical presence in the P. falciparum Mediator.\",\n      \"evidence\": \"Coimmunoprecipitation of PfMed31 coupled with mass spectrometry\",\n      \"pmids\": [\"35557691\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis or functional validation of PfMed14 itself\",\n        \"Predicted scaffold/module-bridging role inferred, not structurally demonstrated\",\n        \"No loss-of-function phenotype established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To place PfMed14 in a broader regulatory context, proximity labeling from a chromatin modifier was used; PfMed14 was detected in the nuclear interaction network of the histone methyltransferase PfSET10, linking it to chromatin-modulation and transcriptional regulation.\",\n      \"evidence\": \"TurboID proximity labeling coupled with mass spectrometry in blood-stage nuclei\",\n      \"pmids\": [\"39445823\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proximity detection only; no direct or reciprocal validation of a PfMed14\\u2013PfSET10 interaction\",\n        \"Functional consequence of the association unknown\",\n        \"Cannot distinguish direct contact from shared nuclear compartment\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what PfMed14 does mechanistically beyond complex membership: no enzymatic activity, structure, essentiality, or loss-of-function phenotype for PfMed14 itself has been established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No conditional knockdown/knockout phenotype for PfMed14\",\n        \"No structural model of PfMed14 within the P. falciparum Mediator\",\n        \"No demonstration of a scaffold/module-bridging function specific to PfMed14\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006357\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"Mediator complex (P. falciparum)\"\n    ],\n    \"partners\": [\n      \"PfMed31 (co-IP/MS)\",\n      \"PfSET10 (proximity labeling)\"\n    ],\n    \"other_free_text\": [\n      \"Detected as a physical Mediator complex member by reciprocal Co-IP/MS of PfMed31 [#0].\",\n      \"Predicted scaffold subunit bridging head, middle, and tail Mediator modules, inferred from homology rather than direct structural evidence [#0, #2].\",\n      \"No enzymatic activity, structural data, or loss-of-function phenotype established for PfMed14 itself in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0709300","name":null,"product":"mediator of RNA polymerase II transcription subunit 14, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1219800","name":null,"product":"mediator of RNA polymerase II transcription subunit 14, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0107900","name":null,"product":"mediator of RNA polymerase II transcription subunit 14, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MED14","evaluation":null}