{"gene":"SCAF11","run_date":"2026-06-10T07:46:29","timeline":{"discoveries":[{"year":2025,"finding":"SCAF11 (a splicing regulator) is co-sequestered in the cytoplasm with TDP-43 pathological aggregates in human iPSC-derived neurons; knockdown of SCAF11 results in aberrant APP alternative splicing and increased amyloid-beta burden, without affecting other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a specific splicing regulatory pathway upstream of APP.","method":"Proximity proteomics, base editing in human iPSC-derived neurons, knockdown with splicing and amyloid-beta readouts","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — proximity proteomics plus functional knockdown in iPSC neurons with specific phenotypic readout, but single lab, preprint, no replication","pmids":["bio_10.1101_2025.04.20.648873"],"is_preprint":true},{"year":2025,"finding":"SCAF11 mediates a competitive ubiquitination mechanism between FOXO1 and METTL14 under conditions of insufficient E3 ligase supply in triple-negative breast cancer cells treated with cold atmospheric plasma (CAP); this competition results in enhanced FOXO1 protein degradation and increased pri-miRNA-146b-5p m6A methylation promoting miRNA-146b-5p maturation.","method":"In vitro and in vivo cancer cell experiments with CAP treatment; mechanistic dissection of competitive protein degradation involving SCAF11, FOXO1, and METTL14","journal":"International journal of biological macromolecules","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single study, limited mechanistic validation details available from abstract alone; no orthogonal confirmation of the competitive ubiquitination model","pmids":["40360112"],"is_preprint":false}],"current_model":"SCAF11 (SFRS2IP/SRSF2IP) functions as a splicing regulator that, when its nuclear activity is disrupted by cytoplasmic TDP-43 co-sequestration, causes aberrant APP alternative splicing and increased amyloid-beta burden; it has also been proposed to mediate competitive ubiquitination between FOXO1 and METTL14, but the mechanistic evidence for this remains limited to a single study."},"narrative":{"mechanistic_narrative":"SCAF11 is a splicing regulator implicated in the control of APP alternative splicing in human neurons [PMID:bio_10.1101_2025.04.20.648873]. In iPSC-derived neurons bearing TDP-43 pathology, SCAF11 is co-sequestered into cytoplasmic TDP-43 aggregates, and its knockdown produces aberrant APP splicing and increased amyloid-beta burden without altering other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a selective splicing pathway upstream of APP [PMID:bio_10.1101_2025.04.20.648873]. A separate line of evidence positions SCAF11 in a competitive ubiquitination mechanism that, under limiting E3 ligase availability, drives FOXO1 degradation versus METTL14 stabilization and downstream m6A methylation of pri-miRNA-146b-5p in triple-negative breast cancer cells [PMID:40360112]. Beyond these two findings, no further mechanistic detail for SCAF11 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Established that SCAF11 acts as a splicing regulator whose mislocalization links TDP-43 pathology to amyloid biology, answering whether a specific splicing factor connects TDP-43 aggregation to APP processing.","evidence":"Proximity proteomics plus base editing and knockdown in human iPSC-derived neurons with splicing and amyloid-beta readouts (preprint)","pmids":["bio_10.1101_2025.04.20.648873"],"confidence":"Medium","gaps":["Single-lab preprint without independent replication","Direct RNA targets and binding mode of SCAF11 on APP transcripts not defined","Whether SCAF11 loss-of-function alone (independent of TDP-43) drives amyloid pathology in vivo is untested"]},{"year":2025,"claim":"Proposed a non-splicing role for SCAF11 in competitive ubiquitination balancing FOXO1 degradation against METTL14 stabilization, addressing how E3 ligase scarcity shapes protein fate in cancer cells.","evidence":"In vitro and in vivo triple-negative breast cancer cell experiments with cold atmospheric plasma treatment and degradation dissection","pmids":["40360112"],"confidence":"Low","gaps":["Single study with limited mechanistic validation and no orthogonal confirmation of the competitive ubiquitination model","Direct enzymatic role of SCAF11 in ubiquitin transfer not demonstrated","Relationship between this cancer-cell function and the neuronal splicing role is unaddressed"]},{"year":null,"claim":"The core molecular activity of SCAF11 — its direct RNA substrates, its physical splicing partners, and whether its splicing and ubiquitination-related roles reflect one biochemical activity — remains undefined.","evidence":"No discovery in the corpus reconstitutes or structurally resolves SCAF11 activity","pmids":[],"confidence":"Low","gaps":["No structural model or biochemical reconstitution","No defined direct binding partners or complex membership","No reconciliation of the neuronal splicing and cancer ubiquitination findings"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q99590","full_name":"Protein SCAF11","aliases":["CTD-associated SR protein 11","Renal carcinoma antigen NY-REN-40","SC35-interacting protein 1","SR-related and CTD-associated factor 11","SRSF2-interacting protein","Serine/arginine-rich splicing factor 2-interacting protein","Splicing factor, arginine/serine-rich 2-interacting protein","Splicing regulatory protein 129","SRrp129"],"length_aa":1463,"mass_kda":164.7,"function":"Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q99590/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SCAF11","classification":"Not Classified","n_dependent_lines":68,"n_total_lines":1208,"dependency_fraction":0.056291390728476824},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CPSF6","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGA1","stoichiometry":0.2},{"gene":"HMGN5","stoichiometry":0.2},{"gene":"SNRPA","stoichiometry":0.2},{"gene":"SNRPB","stoichiometry":0.2},{"gene":"SNRPC","stoichiometry":0.2},{"gene":"SNRPF","stoichiometry":0.2},{"gene":"SSRP1","stoichiometry":0.2},{"gene":"SUPT5H","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/SCAF11","total_profiled":1310},"omim":[{"mim_id":"603668","title":"SR-RELATED C-TERMINAL DOMAIN-ASSOCIATED FACTOR 11; SCAF11","url":"https://www.omim.org/entry/603668"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SCAF11"},"hgnc":{"alias_symbol":["SIP1","SRRP129","CASP11"],"prev_symbol":["SFRS2IP","SRSF2IP"]},"alphafold":{"accession":"Q99590","domains":[{"cath_id":"3.30.40.10","chopping":"37-105","consensus_level":"medium","plddt":84.9865,"start":37,"end":105},{"cath_id":"1.10.8","chopping":"1377-1446","consensus_level":"medium","plddt":88.8186,"start":1377,"end":1446}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99590","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99590-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99590-F1-predicted_aligned_error_v6.png","plddt_mean":42.41},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SCAF11","jax_strain_url":"https://www.jax.org/strain/search?query=SCAF11"},"sequence":{"accession":"Q99590","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99590.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99590/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99590"}},"corpus_meta":[{"pmid":"26677056","id":"PMC_26677056","title":"Improved de novo structure prediction in CASP11 by incorporating coevolution information into Rosetta.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26677056","citation_count":80,"is_preprint":false},{"pmid":"26474083","id":"PMC_26474083","title":"New encouraging developments in contact prediction: Assessment of the CASP11 results.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26474083","citation_count":65,"is_preprint":false},{"pmid":"26370505","id":"PMC_26370505","title":"Integration of QUARK and I-TASSER for Ab Initio Protein Structure Prediction in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26370505","citation_count":55,"is_preprint":false},{"pmid":"26344049","id":"PMC_26344049","title":"Methods of model accuracy estimation can help selecting the best models from decoy sets: Assessment of model accuracy estimations in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26344049","citation_count":55,"is_preprint":false},{"pmid":"26677002","id":"PMC_26677002","title":"Evaluation of free modeling targets in CASP11 and ROLL.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26677002","citation_count":45,"is_preprint":false},{"pmid":"27378298","id":"PMC_27378298","title":"Performance of protein-structure predictions with the physics-based UNRES force field in CASP11.","date":"2016","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/27378298","citation_count":45,"is_preprint":false},{"pmid":"26343917","id":"PMC_26343917","title":"Template-based protein structure prediction in CASP11 and retrospect of I-TASSER in the last decade.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26343917","citation_count":44,"is_preprint":false},{"pmid":"27081793","id":"PMC_27081793","title":"Assessment of refinement of template-based models in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/27081793","citation_count":36,"is_preprint":false},{"pmid":"26857434","id":"PMC_26857434","title":"CASP11 statistics and the prediction center evaluation system.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26857434","citation_count":32,"is_preprint":false},{"pmid":"26329522","id":"PMC_26329522","title":"Template based protein structure modeling by global optimization in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26329522","citation_count":28,"is_preprint":false},{"pmid":"27081927","id":"PMC_27081927","title":"Assessment of template-based modeling of protein structure in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/27081927","citation_count":25,"is_preprint":false},{"pmid":"26205421","id":"PMC_26205421","title":"CASP11 refinement experiments with ROSETTA.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26205421","citation_count":23,"is_preprint":false},{"pmid":"26945814","id":"PMC_26945814","title":"Blind testing of cross-linking/mass spectrometry hybrid methods in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26945814","citation_count":23,"is_preprint":false},{"pmid":"26763289","id":"PMC_26763289","title":"Benchmarking Deep Networks for Predicting Residue-Specific Quality of Individual Protein Models in CASP11.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26763289","citation_count":19,"is_preprint":false},{"pmid":"26857542","id":"PMC_26857542","title":"Structure prediction using sparse simulated NOE restraints with Rosetta in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26857542","citation_count":18,"is_preprint":false},{"pmid":"26344195","id":"PMC_26344195","title":"Protein structure prediction using residue- and fragment-environment potentials in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26344195","citation_count":16,"is_preprint":false},{"pmid":"26493701","id":"PMC_26493701","title":"A large-scale conformation sampling and evaluation server for protein tertiary structure prediction and its assessment in CASP11.","date":"2015","source":"BMC bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/26493701","citation_count":16,"is_preprint":false},{"pmid":"26369671","id":"PMC_26369671","title":"Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26369671","citation_count":16,"is_preprint":false},{"pmid":"26889875","id":"PMC_26889875","title":"Assessment of CASP11 contact-assisted predictions.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26889875","citation_count":15,"is_preprint":false},{"pmid":"26473983","id":"PMC_26473983","title":"Some of the most interesting CASP11 targets through the eyes of their authors.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26473983","citation_count":15,"is_preprint":false},{"pmid":"29967418","id":"PMC_29967418","title":"An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29967418","citation_count":14,"is_preprint":false},{"pmid":"28241391","id":"PMC_28241391","title":"Princeton_TIGRESS 2.0: High refinement consistency and net gains through support vector machines and molecular dynamics in double-blind predictions during the CASP11 experiment.","date":"2017","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/28241391","citation_count":12,"is_preprint":false},{"pmid":"35203520","id":"PMC_35203520","title":"Wedelolactone Attenuates N-methyl-N-nitrosourea-Induced Retinal Neurodegeneration through Suppression of the AIM2/CASP11 Pathway.","date":"2022","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/35203520","citation_count":11,"is_preprint":false},{"pmid":"28317030","id":"PMC_28317030","title":"Blind testing cross-linking/mass spectrometry under the auspices of the 11th critical assessment of methods of protein structure prediction (CASP11).","date":"2016","source":"Wellcome open research","url":"https://pubmed.ncbi.nlm.nih.gov/28317030","citation_count":11,"is_preprint":false},{"pmid":"27046050","id":"PMC_27046050","title":"CASP11--An Evaluation of a Modular BCL::Fold-Based Protein Structure Prediction Pipeline.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27046050","citation_count":10,"is_preprint":false},{"pmid":"26474186","id":"PMC_26474186","title":"Template-free modeling by LEE and LEER in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26474186","citation_count":10,"is_preprint":false},{"pmid":"25990081","id":"PMC_25990081","title":"An Improved Integration of Template-Based and Template-Free Protein Structure Modeling Methods and its Assessment in CASP11.","date":"2015","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/25990081","citation_count":9,"is_preprint":false},{"pmid":"26677100","id":"PMC_26677100","title":"Contact-assisted protein structure modeling by global optimization in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26677100","citation_count":9,"is_preprint":false},{"pmid":"27181425","id":"PMC_27181425","title":"Biological function derived from predicted structures in CASP11.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/27181425","citation_count":8,"is_preprint":false},{"pmid":"38197150","id":"PMC_38197150","title":"Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.","date":"2024","source":"Journal of dental research","url":"https://pubmed.ncbi.nlm.nih.gov/38197150","citation_count":6,"is_preprint":false},{"pmid":"40360112","id":"PMC_40360112","title":"Cold atmospheric plasma targets triple negative breast cancer cells via SCAF11-mediated competitive protein degradation and synergizes with miRNA-146b-5p.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40360112","citation_count":4,"is_preprint":false},{"pmid":"26492194","id":"PMC_26492194","title":"Analysis of free modeling predictions by RBO aleph in CASP11.","date":"2015","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/26492194","citation_count":4,"is_preprint":false},{"pmid":"27701764","id":"PMC_27701764","title":"Modeling and minimizing CAPRI round 30 symmetrical protein complexes from CASP-11 structural models.","date":"2016","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/27701764","citation_count":2,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.01.684729","title":"Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection","date":"2025-11-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.01.684729","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.12.634801","title":"Stress granule component TIA-1 is a negative regulator of the non-canonical NLRP3 inflammasome","date":"2025-07-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.12.634801","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.20.648873","title":"TDP-43 toxic gain of function links ALS, FTD and Alzheimer's Disease through splicing dysregulation","date":"2025-04-24","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.20.648873","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.20.633976","title":"Macrophages orchestrate elimination of  <i>Shigella</i>  from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ","date":"2025-01-22","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.20.633976","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18147,"output_tokens":938,"usd":0.034256,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7027,"output_tokens":1268,"usd":0.033418,"stage2_stop_reason":"end_turn"},"total_usd":0.067674,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify papers about the canonical SCAF11 protein (also known as SRRP129, CASP11/SFRS2IP/SRSF2IP — noting that CASP11 here is an alias for SCAF11, an SR-related protein involved in splicing, NOT the inflammatory caspase-11).\n\nThe vast majority of papers (1-22, 24-29, 32-33) are about the CASP11 protein structure prediction competition, which is a complete symbol collision — these are about a bioinformatics competition, not any protein.\n\nPapers 23, 30, 34, 35, 37 describe inflammatory caspase-11 (the mouse caspase involved in pyroptosis) — this is a different gene (CASP4/CASP5 human orthologs), NOT SCAF11/SFRS2IP.\n\nPaper 31 describes SCAF11 (the canonical splicing factor) in the context of cancer — this is relevant.\n\nPaper 36 describes TDP-43 pathology and mentions SCAF11 as a splicing regulator co-sequestered in cytoplasm — this is relevant.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAF11 (a splicing regulator) is co-sequestered in the cytoplasm with TDP-43 pathological aggregates in human iPSC-derived neurons; knockdown of SCAF11 results in aberrant APP alternative splicing and increased amyloid-beta burden, without affecting other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a specific splicing regulatory pathway upstream of APP.\",\n      \"method\": \"Proximity proteomics, base editing in human iPSC-derived neurons, knockdown with splicing and amyloid-beta readouts\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — proximity proteomics plus functional knockdown in iPSC neurons with specific phenotypic readout, but single lab, preprint, no replication\",\n      \"pmids\": [\"bio_10.1101_2025.04.20.648873\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SCAF11 mediates a competitive ubiquitination mechanism between FOXO1 and METTL14 under conditions of insufficient E3 ligase supply in triple-negative breast cancer cells treated with cold atmospheric plasma (CAP); this competition results in enhanced FOXO1 protein degradation and increased pri-miRNA-146b-5p m6A methylation promoting miRNA-146b-5p maturation.\",\n      \"method\": \"In vitro and in vivo cancer cell experiments with CAP treatment; mechanistic dissection of competitive protein degradation involving SCAF11, FOXO1, and METTL14\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single study, limited mechanistic validation details available from abstract alone; no orthogonal confirmation of the competitive ubiquitination model\",\n      \"pmids\": [\"40360112\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SCAF11 (SFRS2IP/SRSF2IP) functions as a splicing regulator that, when its nuclear activity is disrupted by cytoplasmic TDP-43 co-sequestration, causes aberrant APP alternative splicing and increased amyloid-beta burden; it has also been proposed to mediate competitive ubiquitination between FOXO1 and METTL14, but the mechanistic evidence for this remains limited to a single study.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCAF11 is a splicing regulator implicated in the control of APP alternative splicing in human neurons [#0]. In iPSC-derived neurons bearing TDP-43 pathology, SCAF11 is co-sequestered into cytoplasmic TDP-43 aggregates, and its knockdown produces aberrant APP splicing and increased amyloid-beta burden without altering other TDP-43 splicing targets such as STMN2 or UNC13A, placing SCAF11 in a selective splicing pathway upstream of APP [#0]. A separate line of evidence positions SCAF11 in a competitive ubiquitination mechanism that, under limiting E3 ligase availability, drives FOXO1 degradation versus METTL14 stabilization and downstream m6A methylation of pri-miRNA-146b-5p in triple-negative breast cancer cells [#1]. Beyond these two findings, no further mechanistic detail for SCAF11 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Established that SCAF11 acts as a splicing regulator whose mislocalization links TDP-43 pathology to amyloid biology, answering whether a specific splicing factor connects TDP-43 aggregation to APP processing.\",\n      \"evidence\": \"Proximity proteomics plus base editing and knockdown in human iPSC-derived neurons with splicing and amyloid-beta readouts (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.04.20.648873\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab preprint without independent replication\",\n        \"Direct RNA targets and binding mode of SCAF11 on APP transcripts not defined\",\n        \"Whether SCAF11 loss-of-function alone (independent of TDP-43) drives amyloid pathology in vivo is untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proposed a non-splicing role for SCAF11 in competitive ubiquitination balancing FOXO1 degradation against METTL14 stabilization, addressing how E3 ligase scarcity shapes protein fate in cancer cells.\",\n      \"evidence\": \"In vitro and in vivo triple-negative breast cancer cell experiments with cold atmospheric plasma treatment and degradation dissection\",\n      \"pmids\": [\"40360112\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single study with limited mechanistic validation and no orthogonal confirmation of the competitive ubiquitination model\",\n        \"Direct enzymatic role of SCAF11 in ubiquitin transfer not demonstrated\",\n        \"Relationship between this cancer-cell function and the neuronal splicing role is unaddressed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core molecular activity of SCAF11 — its direct RNA substrates, its physical splicing partners, and whether its splicing and ubiquitination-related roles reflect one biochemical activity — remains undefined.\",\n      \"evidence\": \"No discovery in the corpus reconstitutes or structurally resolves SCAF11 activity\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model or biochemical reconstitution\",\n        \"No defined direct binding partners or complex membership\",\n        \"No reconciliation of the neuronal splicing and cancer ubiquitination findings\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":1,"faith_total":1,"faith_pct":100.0}}