{"gene":"WDR18","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2011,"finding":"WDR18 is a component of a mammalian SENP3-associated complex (PELP1-TEX10-WDR18), biochemically purified and demonstrated to be involved in maturation and nucleolar release of the large (60S) ribosomal subunit; SUMO conjugation/deconjugation of PELP1 controls the nucleolar partitioning of this complex.","method":"Biochemical purification, Co-IP, knockdown with ribosome biogenesis defect readout","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical purification, functional knockdown with defined cellular phenotype, independently replicated across two labs in the same year (PMID:21326211 and PMID:22190735)","pmids":["21326211"],"is_preprint":false},{"year":2011,"finding":"WDR18 (mammalian homolog of yeast Rix1/Ipi3 complex subunit) interacts with LAS1L, PELP1, TEX10, NOL9, and SENP3 to form a nucleolar complex that cofractionates with the 60S preribosomal subunit; depletion of complex members causes defects in processing of pre-rRNA ITS2 and triggers p53-dependent G1 arrest.","method":"Co-immunoprecipitation, sucrose gradient fractionation, siRNA knockdown, pre-rRNA processing assay","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, processing assay, cell-cycle phenotype), replicated finding consistent with PMID:21326211","pmids":["22190735"],"is_preprint":false},{"year":2012,"finding":"WDR18 is a core component of the Five Friends of Methylated Chtop (5FMC) nuclear complex, which also includes PELP1, SENP3, TEX10, and LAS1L; the complex is recruited to chromatin only when Chtop is arginine-methylated by PRMT1, and recruitment of 5FMC to the transcription factor ZBP-89 affects its sumoylation status and transactivation potential, linking arginine methylation to desumoylation in transcriptional control.","method":"Biotinylation-proteomics pulldown, Co-IP, sumoylation assay, transcription reporter assay","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple methods (proteomics, Co-IP, functional reporter), single lab","pmids":["22872859"],"is_preprint":false},{"year":2013,"finding":"WDR18 associates with the C-terminus of TopBP1 in vitro and in vivo (Co-IP and in vitro binding), and also associates with Chk1 in vitro; this association is required for ATR-dependent Chk1 phosphorylation in response to DNA damage, identifying WDR18 as a component of the DNA damage checkpoint signaling pathway.","method":"Co-immunoprecipitation, in vitro binding assay, siRNA knockdown, Chk1 phosphorylation assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP in vivo and in vitro plus functional knockdown with defined phosphorylation readout, single lab","pmids":["23333389"],"is_preprint":false},{"year":2016,"finding":"Human IPI3/WDR18 is required for DNA replication licensing: knockdown of hIPI3 causes defects in chromatin association of the MCM complex, DNA replication, cell cycle progression, and cell proliferation; hIPI3 interacts with other pre-replicative complex proteins, co-localizes with hMCM7 in the nucleus, is required for nuclear localization of hMCM7, and preferentially binds origins of DNA replication (c-Myc, Lamin-B2, β-Globin loci), with mRNA/protein levels peaking from M phase to early G1.","method":"siRNA knockdown, chromatin fractionation, co-immunoprecipitation, ChIP, immunofluorescence, cell cycle analysis","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (knockdown, ChIP, Co-IP, localization), single lab","pmids":["27057756"],"is_preprint":false},{"year":2011,"finding":"Zebrafish wdr18 is expressed in dorsal forerunner cells (DFCs) and Kupffer's vesicle (KV); morpholino knockdown of wdr18 results in fewer and shorter immotile KV cilia, disorganized DFC clustering/migration, mis-expression of Nodal-related genes (spaw, pitx2), and laterality defects in visceral organs; genetic interaction with itgb1b was demonstrated by double morpholino injection.","method":"Morpholino knockdown, in situ hybridization, cilia motility analysis, genetic epistasis (double morpholino)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined developmental phenotype and genetic interaction, single lab, zebrafish ortholog","pmids":["21876750"],"is_preprint":false},{"year":2022,"finding":"Cryo-EM structure of the human PELP1 Rix1 domain–WDR18 subcomplex at 2.7 Å resolution reveals an interconnected tetrameric assembly (PELP12-WDR182); the structure shows the architecture of PELP1's eleven LxxLL signaling motifs but demonstrates that none is in a conformation compatible with steroid receptor binding, suggesting that WDR18 association directs PELP1 activity away from steroid receptor coactivation.","method":"Cryo-EM structure determination (2.7 Å), complex reconstitution, mutagenesis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — near-atomic cryo-EM structure with reconstitution and mutagenesis validation in a single rigorous study","pmids":["36351913"],"is_preprint":false},{"year":2004,"finding":"Yeast Ipi3 (ortholog of WDR18) is a component of the Rix1 complex (Rix1-Ipi1-Ipi3); strains depleted of Ipi3 show defects in pre-rRNA processing and late pre-60S ribosome stability (after ITS2 cleavage, before mature 5.8S rRNA generation), and nuclear accumulation of Rpl25-GFP, phenocopying Rea1 depletion.","method":"GAL::repressible depletion, pre-rRNA processing analysis (Northern blot), in vivo 60S export assay (Rpl25-GFP)","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic depletion with multiple orthogonal readouts (processing, export assay), foundational yeast ortholog study","pmids":["15528184"],"is_preprint":false},{"year":2020,"finding":"Cryo-EM analysis of yeast pre-60S intermediates reveals that the Rix1 complex (including Ipi3/WDR18 ortholog) forms a Rix12-Ipi32 tetramer anchored via Ipi1 to the pre-ribosome, positioned to monitor central protuberance formation and coordinate with the AAA-ATPase Rea1 during two successive structural remodeling steps of 60S maturation.","method":"Cryo-EM structural analysis of pre-60S intermediates","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM at molecular resolution with structural context for the complex, yeast ortholog study","pmids":["32668200"],"is_preprint":false},{"year":2023,"finding":"Cryo-EM and biochemical analysis of the rixosome from Chaetomium thermophilum (ortholog of human complex) shows that the Rix1-Ipi3-Ipi1 sphere sub-module (containing Ipi3/WDR18 ortholog) uses Sda1 as a landing platform on nucleoplasmic pre-60S particles, wedges between the 5S rRNA tip and L1-stalk to facilitate 180° rotation of the immature 5S RNP, and positions the Las1-Grc3 catalytic module for ITS2 cleavage.","method":"Cryo-EM structure, biochemical complex isolation, mutagenesis","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structural determination with mechanistic functional context, fungal ortholog study","pmids":["37921038"],"is_preprint":false},{"year":2025,"finding":"Cryo-EM structures of human PELP1-WDR18-TEX10 and LAS1L-NOL9 complexes, and a lower-resolution model of PELP1-WDR18-LAS1L, reveal the overall organization of the human rixosome core scaffold; WDR18 contacts TEX10 at two regions (mutagenesis of either blocks TEX10 binding) and its C-terminal helix contacts the helical domain of LAS1L (truncation abolishes LAS1L binding), establishing WDR18 as a central scaffold bridging the catalytic LAS1L-NOL9 module to the PELP1-TEX10 core.","method":"Cryo-EM structure determination, site-directed mutagenesis, binding assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM with mutagenesis validation of specific interaction interfaces, multiple orthogonal structural and biochemical methods","pmids":["40195365"],"is_preprint":false},{"year":2026,"finding":"WDR18 is a substrate receptor subunit of the CRL4B E3 ubiquitin ligase complex (CRL4BWDR18); halofuginone acts as a molecular glue degrader that promotes integrin β4 degradation via this CRL4BWDR18 complex.","method":"High-throughput screening, degradation assays in vitro and in vivo, E3 ligase complex identification","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional degradation assay with complex identification, single lab, abstract does not detail mechanistic validation depth","pmids":["41874446"],"is_preprint":false},{"year":2006,"finding":"C. elegans PRO-1, the ortholog of yeast IPI3/WDR18, influences rRNA processing (as shown by suppression of pro-1 germline tumors by mutations in ncl-1 or lin-35/Rb that elevate pre-rRNA levels), establishing a role for this protein in ribosome biogenesis that non-autonomously affects germline proliferation.","method":"Genetic epistasis (suppressor mutations), rRNA processing analysis, morphological phenotype scoring","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with functional pre-rRNA processing link, C. elegans ortholog, single lab","pmids":["16876152"],"is_preprint":false}],"current_model":"WDR18 (human IPI3) is a WD40-repeat scaffolding protein that functions as a core structural subunit of the mammalian rixosome/Rix1 complex (PELP1–WDR18–TEX10–LAS1L–NOL9), where it bridges the catalytic LAS1L-NOL9 endonuclease/kinase module to the PELP1-TEX10 scaffold via two TEX10-contact regions and a C-terminal helix that docks LAS1L; this complex mediates ITS2 pre-rRNA processing, 5S RNP rotation, and nucleolar release of the 60S ribosomal subunit in a pathway regulated by SENP3-dependent SUMO deconjugation of PELP1; independently, WDR18 associates with TopBP1 and Chk1 to facilitate ATR-dependent checkpoint signaling, participates in DNA replication licensing by promoting MCM chromatin loading and binding replication origins, and serves as a substrate receptor of the CRL4B E3 ubiquitin ligase complex."},"narrative":{"mechanistic_narrative":"WDR18 (human IPI3) is a WD40-repeat scaffolding protein that functions as a core structural subunit of the nucleolar rixosome/Rix1 complex (PELP1–WDR18–TEX10–LAS1L–NOL9), which drives maturation and nucleolar release of the large (60S) ribosomal subunit [PMID:21326211, PMID:22190735, PMID:15528184]. Within this complex WDR18 acts as a central bridge: its two TEX10-contact regions tether it to the PELP1–TEX10 core while a C-terminal helix docks the catalytic LAS1L–NOL9 endonuclease/kinase module, coupling scaffold assembly to ITS2 pre-rRNA processing [PMID:40195365]. Structural work on the human PELP1 Rix1 domain–WDR18 subcomplex shows an interconnected PELP1₂–WDR18₂ tetramer in which WDR18 association sequesters PELP1's LxxLL motifs away from steroid-receptor-coactivation conformations [PMID:36351913], and orthologous cryo-EM analyses establish that this Rix1–Ipi3–Ipi1 module wedges between the 5S rRNA and L1-stalk to drive 180° rotation of the immature 5S RNP and to position the Las1–Grc3 module for ITS2 cleavage [PMID:32668200, PMID:37921038]. Depletion of WDR18 or its complex partners blocks ITS2 processing and triggers p53-dependent G1 arrest [PMID:22190735], and its conserved role in ribosome biogenesis extends to non-autonomous control of germline proliferation in invertebrate orthologs [PMID:16876152]. WDR18 is also recruited, via arginine-methylated Chtop, into the 5FMC chromatin complex that modulates SUMO status and transactivation of ZBP-89 [PMID:22872859]. Beyond ribosome biogenesis, WDR18 associates with TopBP1 and Chk1 to support ATR-dependent checkpoint signaling [PMID:23333389], promotes MCM chromatin loading and binds replication origins during licensing [PMID:27057756], and serves as a substrate receptor of the CRL4B E3 ubiquitin ligase, where halofuginone acts as a molecular glue to drive integrin β4 degradation [PMID:41874446].","teleology":[{"year":2004,"claim":"Established the founding role of the WDR18 ortholog by showing that yeast Ipi3 is a Rix1 complex subunit required for late pre-60S maturation, answering whether this WD-repeat protein acts in ribosome biogenesis.","evidence":"GAL-repressible depletion with Northern pre-rRNA analysis and Rpl25-GFP export assay in yeast","pmids":["15528184"],"confidence":"High","gaps":["Did not define which subunit interfaces Ipi3 contacts","Mammalian conservation not addressed"]},{"year":2006,"claim":"Extended the ribosome-biogenesis function to a metazoan ortholog and linked it to tissue proliferation, showing C. elegans PRO-1 affects rRNA processing and non-autonomously controls germline proliferation.","evidence":"Genetic epistasis with ncl-1/lin-35 suppressors and rRNA processing analysis in C. elegans","pmids":["16876152"],"confidence":"Medium","gaps":["No biochemical complex definition","Mechanism of non-autonomous proliferation control unresolved"]},{"year":2011,"claim":"Defined the mammalian complex and its regulation, establishing WDR18 as a SENP3-associated PELP1-TEX10-LAS1L-NOL9 subunit needed for 60S maturation/nucleolar release, with SUMO controlling complex partitioning and depletion triggering p53-dependent G1 arrest.","evidence":"Biochemical purification, Co-IP, sucrose gradient fractionation, siRNA knockdown and pre-rRNA processing assays (two independent labs)","pmids":["21326211","22190735"],"confidence":"High","gaps":["Did not resolve subunit architecture or contact interfaces","Direct enzymatic role of WDR18 not defined"]},{"year":2012,"claim":"Revealed a chromatin-linked function distinct from ribosome biogenesis, showing WDR18 is part of the 5FMC complex recruited by arginine-methylated Chtop to regulate ZBP-89 sumoylation and transactivation.","evidence":"Biotinylation-proteomics, Co-IP, sumoylation and transcription reporter assays in human cells (single lab)","pmids":["22872859"],"confidence":"Medium","gaps":["Whether 5FMC and rixosome are the same or distinct assemblies unclear","Direct WDR18 contribution to desumoylation activity not isolated"]},{"year":2013,"claim":"Implicated WDR18 in DNA damage signaling, showing it binds TopBP1 and Chk1 and is required for ATR-dependent Chk1 phosphorylation.","evidence":"Co-IP in vivo and in vitro binding, siRNA knockdown with Chk1 phosphorylation readout (single lab)","pmids":["23333389"],"confidence":"Medium","gaps":["No reciprocal validation of direct binding","Relationship to the nucleolar complex function unestablished"]},{"year":2016,"claim":"Identified a replication-licensing role, showing WDR18 promotes MCM chromatin loading, hMCM7 nuclear localization, and binds replication origins with cell-cycle-regulated expression.","evidence":"siRNA knockdown, chromatin fractionation, ChIP, Co-IP and immunofluorescence in human cells (single lab)","pmids":["27057756"],"confidence":"Medium","gaps":["Direct vs. indirect role in origin binding unresolved","Mechanistic overlap with checkpoint and rixosome functions not reconciled"]},{"year":2022,"claim":"Provided the first near-atomic view of the human PELP1–WDR18 subcomplex, resolving a PELP1₂-WDR18₂ tetramer and showing WDR18 binding directs PELP1 away from steroid-receptor coactivation.","evidence":"Cryo-EM at 2.7 Å with reconstitution and mutagenesis","pmids":["36351913"],"confidence":"High","gaps":["Catalytic module not included in the structure","Functional consequence on pre-rRNA processing not directly tested"]},{"year":2023,"claim":"Defined the mechanistic action of the Ipi3-containing sphere module on pre-60S particles, showing it lands via Sda1, drives 5S RNP rotation, and positions the Las1-Grc3 module for ITS2 cleavage.","evidence":"Cryo-EM, biochemical complex isolation and mutagenesis in C. thermophilum (ortholog)","pmids":["37921038"],"confidence":"High","gaps":["Human-specific structural confirmation pending","Dynamics of rotation step not temporally resolved"]},{"year":2025,"claim":"Established WDR18 as the central scaffold of the human rixosome core, mapping two TEX10-contact regions and a C-terminal helix that docks LAS1L, bridging the catalytic module to the PELP1-TEX10 core.","evidence":"Cryo-EM structures with site-directed mutagenesis and binding assays of human subcomplexes","pmids":["40195365"],"confidence":"High","gaps":["Full intact rixosome on the pre-60S not resolved at high resolution","Regulation of bridging by SUMO/methylation not structurally captured"]},{"year":2026,"claim":"Uncovered an E3 ligase function, identifying WDR18 as a CRL4B substrate receptor exploited by halofuginone as a molecular glue to degrade integrin β4.","evidence":"High-throughput screening, in vitro and in vivo degradation assays, ligase complex identification (single lab)","pmids":["41874446"],"confidence":"Medium","gaps":["Mechanistic validation depth limited","Endogenous substrates and relationship to nucleolar role undefined"]},{"year":null,"claim":"How WDR18's distinct activities—rixosome scaffolding, replication licensing, checkpoint signaling, transcriptional regulation, and CRL4B substrate-receptor function—are partitioned and regulated within a single protein remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No study reconciles nucleolar vs. nuclear/replication functions","Whether E3 ligase and rixosome roles use the same WD40 surface is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[10,6]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,9]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,4]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,7]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[8,9]},{"term_id":"R-HSA-69306","term_label":"DNA Replication","supporting_discovery_ids":[4]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[3]}],"complexes":["rixosome/Rix1 complex (PELP1-WDR18-TEX10-LAS1L-NOL9)","5FMC complex","CRL4B E3 ubiquitin ligase"],"partners":["PELP1","TEX10","LAS1L","NOL9","SENP3","TOPBP1","CHK1","MCM7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BV38","full_name":"WD repeat-containing protein 18","aliases":[],"length_aa":432,"mass_kda":47.4,"function":"Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211). May play a role during development (By similarity)","subcellular_location":"Nucleus, nucleolus; Nucleus, nucleoplasm; Cytoplasm; Dynein axonemal particle","url":"https://www.uniprot.org/uniprotkb/Q9BV38/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR18","classification":"Common Essential","n_dependent_lines":1174,"n_total_lines":1208,"dependency_fraction":0.9718543046357616},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CBX1","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"SRP68","stoichiometry":0.2},{"gene":"SRP9","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/WDR18","total_profiled":1310},"omim":[{"mim_id":"620291","title":"WD REPEAT-CONTAINING PROTEIN 18; WDR18","url":"https://www.omim.org/entry/620291"},{"mim_id":"616717","title":"TESTIS-EXPRESSED GENE 10; TEX10","url":"https://www.omim.org/entry/616717"},{"mim_id":"609455","title":"PROLINE-, GLUTAMIC ACID-, AND LEUCINE-RICH PROTEIN 1; PELP1","url":"https://www.omim.org/entry/609455"},{"mim_id":"607760","title":"DNA TOPOISOMERASE II-BINDING PROTEIN 1; TOPBP1","url":"https://www.omim.org/entry/607760"},{"mim_id":"603078","title":"CHECKPOINT KINASE 1; CHEK1","url":"https://www.omim.org/entry/603078"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/WDR18"},"hgnc":{"alias_symbol":["Ipi3"],"prev_symbol":[]},"alphafold":{"accession":"Q9BV38","domains":[{"cath_id":"2.130.10.10","chopping":"7-326","consensus_level":"high","plddt":91.9082,"start":7,"end":326}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV38","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV38-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV38-F1-predicted_aligned_error_v6.png","plddt_mean":85.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR18","jax_strain_url":"https://www.jax.org/strain/search?query=WDR18"},"sequence":{"accession":"Q9BV38","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BV38.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BV38/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV38"}},"corpus_meta":[{"pmid":"29106665","id":"PMC_29106665","title":"Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143.","date":"2018","source":"Neuro-oncology","url":"https://pubmed.ncbi.nlm.nih.gov/29106665","citation_count":397,"is_preprint":false},{"pmid":"21326211","id":"PMC_21326211","title":"The SUMO system controls nucleolar partitioning of a novel mammalian ribosome biogenesis complex.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21326211","citation_count":110,"is_preprint":false},{"pmid":"22190735","id":"PMC_22190735","title":"LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22190735","citation_count":89,"is_preprint":false},{"pmid":"15528184","id":"PMC_15528184","title":"Rea1, a dynein-related nuclear AAA-ATPase, is involved in late rRNA processing and nuclear export of 60 S subunits.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15528184","citation_count":62,"is_preprint":false},{"pmid":"22064470","id":"PMC_22064470","title":"SUMO routes ribosome maturation.","date":"2011","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/22064470","citation_count":61,"is_preprint":false},{"pmid":"38608691","id":"PMC_38608691","title":"Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.","date":"2024","source":"The Lancet. 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Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/30890025","citation_count":6,"is_preprint":false},{"pmid":"39719505","id":"PMC_39719505","title":"An atlas of the shared genetic architecture between atopic and gastrointestinal diseases.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39719505","citation_count":4,"is_preprint":false},{"pmid":"40195365","id":"PMC_40195365","title":"Molecular insights into the overall architecture of human rixosome.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/40195365","citation_count":3,"is_preprint":false},{"pmid":"40677927","id":"PMC_40677927","title":"Whole Genome Sequencing of \"Mutation-Negative\" Individuals With Cornelia de Lange Syndrome.","date":"2025","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/40677927","citation_count":1,"is_preprint":false},{"pmid":"40136348","id":"PMC_40136348","title":"Dramatic Responses to High-Dose Ipilimumab Plus Temozolomide After Progression on Standard- or Low-Dose Ipilimumab in Advanced Melanoma.","date":"2025","source":"Current oncology (Toronto, Ont.)","url":"https://pubmed.ncbi.nlm.nih.gov/40136348","citation_count":1,"is_preprint":false},{"pmid":"37398360","id":"PMC_37398360","title":"Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.","date":"2023","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/37398360","citation_count":1,"is_preprint":false},{"pmid":"40723429","id":"PMC_40723429","title":"Molecular Mechanism of Body Color Change in the Ecological Seedling Breeding Model of Apostichopus japonicus.","date":"2025","source":"Biology","url":"https://pubmed.ncbi.nlm.nih.gov/40723429","citation_count":1,"is_preprint":false},{"pmid":"41874446","id":"PMC_41874446","title":"Halofuginone is a Molecular Glue Degrader of Integrin β4.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/41874446","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17534,"output_tokens":3555,"usd":0.052963,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11039,"output_tokens":3832,"usd":0.075497,"stage2_stop_reason":"end_turn"},"total_usd":0.12846,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"WDR18 is a component of a mammalian SENP3-associated complex (PELP1-TEX10-WDR18), biochemically purified and demonstrated to be involved in maturation and nucleolar release of the large (60S) ribosomal subunit; SUMO conjugation/deconjugation of PELP1 controls the nucleolar partitioning of this complex.\",\n      \"method\": \"Biochemical purification, Co-IP, knockdown with ribosome biogenesis defect readout\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical purification, functional knockdown with defined cellular phenotype, independently replicated across two labs in the same year (PMID:21326211 and PMID:22190735)\",\n      \"pmids\": [\"21326211\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"WDR18 (mammalian homolog of yeast Rix1/Ipi3 complex subunit) interacts with LAS1L, PELP1, TEX10, NOL9, and SENP3 to form a nucleolar complex that cofractionates with the 60S preribosomal subunit; depletion of complex members causes defects in processing of pre-rRNA ITS2 and triggers p53-dependent G1 arrest.\",\n      \"method\": \"Co-immunoprecipitation, sucrose gradient fractionation, siRNA knockdown, pre-rRNA processing assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, fractionation, processing assay, cell-cycle phenotype), replicated finding consistent with PMID:21326211\",\n      \"pmids\": [\"22190735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"WDR18 is a core component of the Five Friends of Methylated Chtop (5FMC) nuclear complex, which also includes PELP1, SENP3, TEX10, and LAS1L; the complex is recruited to chromatin only when Chtop is arginine-methylated by PRMT1, and recruitment of 5FMC to the transcription factor ZBP-89 affects its sumoylation status and transactivation potential, linking arginine methylation to desumoylation in transcriptional control.\",\n      \"method\": \"Biotinylation-proteomics pulldown, Co-IP, sumoylation assay, transcription reporter assay\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple methods (proteomics, Co-IP, functional reporter), single lab\",\n      \"pmids\": [\"22872859\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"WDR18 associates with the C-terminus of TopBP1 in vitro and in vivo (Co-IP and in vitro binding), and also associates with Chk1 in vitro; this association is required for ATR-dependent Chk1 phosphorylation in response to DNA damage, identifying WDR18 as a component of the DNA damage checkpoint signaling pathway.\",\n      \"method\": \"Co-immunoprecipitation, in vitro binding assay, siRNA knockdown, Chk1 phosphorylation assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP in vivo and in vitro plus functional knockdown with defined phosphorylation readout, single lab\",\n      \"pmids\": [\"23333389\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Human IPI3/WDR18 is required for DNA replication licensing: knockdown of hIPI3 causes defects in chromatin association of the MCM complex, DNA replication, cell cycle progression, and cell proliferation; hIPI3 interacts with other pre-replicative complex proteins, co-localizes with hMCM7 in the nucleus, is required for nuclear localization of hMCM7, and preferentially binds origins of DNA replication (c-Myc, Lamin-B2, β-Globin loci), with mRNA/protein levels peaking from M phase to early G1.\",\n      \"method\": \"siRNA knockdown, chromatin fractionation, co-immunoprecipitation, ChIP, immunofluorescence, cell cycle analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (knockdown, ChIP, Co-IP, localization), single lab\",\n      \"pmids\": [\"27057756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Zebrafish wdr18 is expressed in dorsal forerunner cells (DFCs) and Kupffer's vesicle (KV); morpholino knockdown of wdr18 results in fewer and shorter immotile KV cilia, disorganized DFC clustering/migration, mis-expression of Nodal-related genes (spaw, pitx2), and laterality defects in visceral organs; genetic interaction with itgb1b was demonstrated by double morpholino injection.\",\n      \"method\": \"Morpholino knockdown, in situ hybridization, cilia motility analysis, genetic epistasis (double morpholino)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined developmental phenotype and genetic interaction, single lab, zebrafish ortholog\",\n      \"pmids\": [\"21876750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Cryo-EM structure of the human PELP1 Rix1 domain–WDR18 subcomplex at 2.7 Å resolution reveals an interconnected tetrameric assembly (PELP12-WDR182); the structure shows the architecture of PELP1's eleven LxxLL signaling motifs but demonstrates that none is in a conformation compatible with steroid receptor binding, suggesting that WDR18 association directs PELP1 activity away from steroid receptor coactivation.\",\n      \"method\": \"Cryo-EM structure determination (2.7 Å), complex reconstitution, mutagenesis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — near-atomic cryo-EM structure with reconstitution and mutagenesis validation in a single rigorous study\",\n      \"pmids\": [\"36351913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Yeast Ipi3 (ortholog of WDR18) is a component of the Rix1 complex (Rix1-Ipi1-Ipi3); strains depleted of Ipi3 show defects in pre-rRNA processing and late pre-60S ribosome stability (after ITS2 cleavage, before mature 5.8S rRNA generation), and nuclear accumulation of Rpl25-GFP, phenocopying Rea1 depletion.\",\n      \"method\": \"GAL::repressible depletion, pre-rRNA processing analysis (Northern blot), in vivo 60S export assay (Rpl25-GFP)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic depletion with multiple orthogonal readouts (processing, export assay), foundational yeast ortholog study\",\n      \"pmids\": [\"15528184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM analysis of yeast pre-60S intermediates reveals that the Rix1 complex (including Ipi3/WDR18 ortholog) forms a Rix12-Ipi32 tetramer anchored via Ipi1 to the pre-ribosome, positioned to monitor central protuberance formation and coordinate with the AAA-ATPase Rea1 during two successive structural remodeling steps of 60S maturation.\",\n      \"method\": \"Cryo-EM structural analysis of pre-60S intermediates\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM at molecular resolution with structural context for the complex, yeast ortholog study\",\n      \"pmids\": [\"32668200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Cryo-EM and biochemical analysis of the rixosome from Chaetomium thermophilum (ortholog of human complex) shows that the Rix1-Ipi3-Ipi1 sphere sub-module (containing Ipi3/WDR18 ortholog) uses Sda1 as a landing platform on nucleoplasmic pre-60S particles, wedges between the 5S rRNA tip and L1-stalk to facilitate 180° rotation of the immature 5S RNP, and positions the Las1-Grc3 catalytic module for ITS2 cleavage.\",\n      \"method\": \"Cryo-EM structure, biochemical complex isolation, mutagenesis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structural determination with mechanistic functional context, fungal ortholog study\",\n      \"pmids\": [\"37921038\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cryo-EM structures of human PELP1-WDR18-TEX10 and LAS1L-NOL9 complexes, and a lower-resolution model of PELP1-WDR18-LAS1L, reveal the overall organization of the human rixosome core scaffold; WDR18 contacts TEX10 at two regions (mutagenesis of either blocks TEX10 binding) and its C-terminal helix contacts the helical domain of LAS1L (truncation abolishes LAS1L binding), establishing WDR18 as a central scaffold bridging the catalytic LAS1L-NOL9 module to the PELP1-TEX10 core.\",\n      \"method\": \"Cryo-EM structure determination, site-directed mutagenesis, binding assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM with mutagenesis validation of specific interaction interfaces, multiple orthogonal structural and biochemical methods\",\n      \"pmids\": [\"40195365\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"WDR18 is a substrate receptor subunit of the CRL4B E3 ubiquitin ligase complex (CRL4BWDR18); halofuginone acts as a molecular glue degrader that promotes integrin β4 degradation via this CRL4BWDR18 complex.\",\n      \"method\": \"High-throughput screening, degradation assays in vitro and in vivo, E3 ligase complex identification\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional degradation assay with complex identification, single lab, abstract does not detail mechanistic validation depth\",\n      \"pmids\": [\"41874446\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"C. elegans PRO-1, the ortholog of yeast IPI3/WDR18, influences rRNA processing (as shown by suppression of pro-1 germline tumors by mutations in ncl-1 or lin-35/Rb that elevate pre-rRNA levels), establishing a role for this protein in ribosome biogenesis that non-autonomously affects germline proliferation.\",\n      \"method\": \"Genetic epistasis (suppressor mutations), rRNA processing analysis, morphological phenotype scoring\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with functional pre-rRNA processing link, C. elegans ortholog, single lab\",\n      \"pmids\": [\"16876152\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR18 (human IPI3) is a WD40-repeat scaffolding protein that functions as a core structural subunit of the mammalian rixosome/Rix1 complex (PELP1–WDR18–TEX10–LAS1L–NOL9), where it bridges the catalytic LAS1L-NOL9 endonuclease/kinase module to the PELP1-TEX10 scaffold via two TEX10-contact regions and a C-terminal helix that docks LAS1L; this complex mediates ITS2 pre-rRNA processing, 5S RNP rotation, and nucleolar release of the 60S ribosomal subunit in a pathway regulated by SENP3-dependent SUMO deconjugation of PELP1; independently, WDR18 associates with TopBP1 and Chk1 to facilitate ATR-dependent checkpoint signaling, participates in DNA replication licensing by promoting MCM chromatin loading and binding replication origins, and serves as a substrate receptor of the CRL4B E3 ubiquitin ligase complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR18 (human IPI3) is a WD40-repeat scaffolding protein that functions as a core structural subunit of the nucleolar rixosome/Rix1 complex (PELP1\\u2013WDR18\\u2013TEX10\\u2013LAS1L\\u2013NOL9), which drives maturation and nucleolar release of the large (60S) ribosomal subunit [#0, #1, #7]. Within this complex WDR18 acts as a central bridge: its two TEX10-contact regions tether it to the PELP1\\u2013TEX10 core while a C-terminal helix docks the catalytic LAS1L\\u2013NOL9 endonuclease/kinase module, coupling scaffold assembly to ITS2 pre-rRNA processing [#10]. Structural work on the human PELP1 Rix1 domain\\u2013WDR18 subcomplex shows an interconnected PELP1\\u2082\\u2013WDR18\\u2082 tetramer in which WDR18 association sequesters PELP1's LxxLL motifs away from steroid-receptor-coactivation conformations [#6], and orthologous cryo-EM analyses establish that this Rix1\\u2013Ipi3\\u2013Ipi1 module wedges between the 5S rRNA and L1-stalk to drive 180\\u00b0 rotation of the immature 5S RNP and to position the Las1\\u2013Grc3 module for ITS2 cleavage [#8, #9]. Depletion of WDR18 or its complex partners blocks ITS2 processing and triggers p53-dependent G1 arrest [#1], and its conserved role in ribosome biogenesis extends to non-autonomous control of germline proliferation in invertebrate orthologs [#12]. WDR18 is also recruited, via arginine-methylated Chtop, into the 5FMC chromatin complex that modulates SUMO status and transactivation of ZBP-89 [#2]. Beyond ribosome biogenesis, WDR18 associates with TopBP1 and Chk1 to support ATR-dependent checkpoint signaling [#3], promotes MCM chromatin loading and binds replication origins during licensing [#4], and serves as a substrate receptor of the CRL4B E3 ubiquitin ligase, where halofuginone acts as a molecular glue to drive integrin \\u03b24 degradation [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established the founding role of the WDR18 ortholog by showing that yeast Ipi3 is a Rix1 complex subunit required for late pre-60S maturation, answering whether this WD-repeat protein acts in ribosome biogenesis.\",\n      \"evidence\": \"GAL-repressible depletion with Northern pre-rRNA analysis and Rpl25-GFP export assay in yeast\",\n      \"pmids\": [\"15528184\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define which subunit interfaces Ipi3 contacts\", \"Mammalian conservation not addressed\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Extended the ribosome-biogenesis function to a metazoan ortholog and linked it to tissue proliferation, showing C. elegans PRO-1 affects rRNA processing and non-autonomously controls germline proliferation.\",\n      \"evidence\": \"Genetic epistasis with ncl-1/lin-35 suppressors and rRNA processing analysis in C. elegans\",\n      \"pmids\": [\"16876152\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No biochemical complex definition\", \"Mechanism of non-autonomous proliferation control unresolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Defined the mammalian complex and its regulation, establishing WDR18 as a SENP3-associated PELP1-TEX10-LAS1L-NOL9 subunit needed for 60S maturation/nucleolar release, with SUMO controlling complex partitioning and depletion triggering p53-dependent G1 arrest.\",\n      \"evidence\": \"Biochemical purification, Co-IP, sucrose gradient fractionation, siRNA knockdown and pre-rRNA processing assays (two independent labs)\",\n      \"pmids\": [\"21326211\", \"22190735\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve subunit architecture or contact interfaces\", \"Direct enzymatic role of WDR18 not defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Revealed a chromatin-linked function distinct from ribosome biogenesis, showing WDR18 is part of the 5FMC complex recruited by arginine-methylated Chtop to regulate ZBP-89 sumoylation and transactivation.\",\n      \"evidence\": \"Biotinylation-proteomics, Co-IP, sumoylation and transcription reporter assays in human cells (single lab)\",\n      \"pmids\": [\"22872859\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether 5FMC and rixosome are the same or distinct assemblies unclear\", \"Direct WDR18 contribution to desumoylation activity not isolated\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Implicated WDR18 in DNA damage signaling, showing it binds TopBP1 and Chk1 and is required for ATR-dependent Chk1 phosphorylation.\",\n      \"evidence\": \"Co-IP in vivo and in vitro binding, siRNA knockdown with Chk1 phosphorylation readout (single lab)\",\n      \"pmids\": [\"23333389\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reciprocal validation of direct binding\", \"Relationship to the nucleolar complex function unestablished\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified a replication-licensing role, showing WDR18 promotes MCM chromatin loading, hMCM7 nuclear localization, and binds replication origins with cell-cycle-regulated expression.\",\n      \"evidence\": \"siRNA knockdown, chromatin fractionation, ChIP, Co-IP and immunofluorescence in human cells (single lab)\",\n      \"pmids\": [\"27057756\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. indirect role in origin binding unresolved\", \"Mechanistic overlap with checkpoint and rixosome functions not reconciled\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Provided the first near-atomic view of the human PELP1\\u2013WDR18 subcomplex, resolving a PELP1\\u2082-WDR18\\u2082 tetramer and showing WDR18 binding directs PELP1 away from steroid-receptor coactivation.\",\n      \"evidence\": \"Cryo-EM at 2.7 \\u00c5 with reconstitution and mutagenesis\",\n      \"pmids\": [\"36351913\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Catalytic module not included in the structure\", \"Functional consequence on pre-rRNA processing not directly tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the mechanistic action of the Ipi3-containing sphere module on pre-60S particles, showing it lands via Sda1, drives 5S RNP rotation, and positions the Las1-Grc3 module for ITS2 cleavage.\",\n      \"evidence\": \"Cryo-EM, biochemical complex isolation and mutagenesis in C. thermophilum (ortholog)\",\n      \"pmids\": [\"37921038\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Human-specific structural confirmation pending\", \"Dynamics of rotation step not temporally resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established WDR18 as the central scaffold of the human rixosome core, mapping two TEX10-contact regions and a C-terminal helix that docks LAS1L, bridging the catalytic module to the PELP1-TEX10 core.\",\n      \"evidence\": \"Cryo-EM structures with site-directed mutagenesis and binding assays of human subcomplexes\",\n      \"pmids\": [\"40195365\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full intact rixosome on the pre-60S not resolved at high resolution\", \"Regulation of bridging by SUMO/methylation not structurally captured\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Uncovered an E3 ligase function, identifying WDR18 as a CRL4B substrate receptor exploited by halofuginone as a molecular glue to degrade integrin \\u03b24.\",\n      \"evidence\": \"High-throughput screening, in vitro and in vivo degradation assays, ligase complex identification (single lab)\",\n      \"pmids\": [\"41874446\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic validation depth limited\", \"Endogenous substrates and relationship to nucleolar role undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How WDR18's distinct activities\\u2014rixosome scaffolding, replication licensing, checkpoint signaling, transcriptional regulation, and CRL4B substrate-receptor function\\u2014are partitioned and regulated within a single protein remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No study reconciles nucleolar vs. nuclear/replication functions\", \"Whether E3 ligase and rixosome roles use the same WD40 surface is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [10, 6]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 7]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [8, 9]},\n      {\"term_id\": \"R-HSA-69306\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"rixosome/Rix1 complex (PELP1-WDR18-TEX10-LAS1L-NOL9)\",\n      \"5FMC complex\",\n      \"CRL4B E3 ubiquitin ligase\"\n    ],\n    \"partners\": [\n      \"PELP1\",\n      \"TEX10\",\n      \"LAS1L\",\n      \"NOL9\",\n      \"SENP3\",\n      \"TopBP1\",\n      \"Chk1\",\n      \"MCM7\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}