{"gene":"WDR12","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2005,"finding":"WDR12 forms a stable trimeric complex with Pes1 and Bop1 (PeBoW complex) in mammalian cells. WDR12 is required for processing of the 32S precursor rRNA. A dominant-negative mutant of WDR12 blocks rRNA processing and induces reversible cell cycle arrest, triggering p53 accumulation in a p19ARF-independent manner in proliferating but not quiescent cells.","method":"Co-immunoprecipitation, dominant-negative expression, cell fractionation, rRNA processing assays, p53 accumulation assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, dominant-negative mutagenesis, rRNA processing assays, and p53 pathway placement in a focused mechanistic study; replicated in subsequent work","pmids":["16043514"],"is_preprint":false},{"year":2007,"finding":"Bop1 is the integral scaffold of the PeBoW complex: knockdown of Bop1 abolishes copurification of Pes1 with WDR12, while recombinant expression of all three subunits (Pes1, Bop1, WDR12) is sufficient for complex formation. WDR12 nucleolar localization depends on its incorporation into the PeBoW complex. Overexpression of Bop1 inhibits cell proliferation and rRNA processing, and coexpression of WDR12 (but not Pes1) rescues these negative effects.","method":"Recombinant co-expression, Co-immunoprecipitation, siRNA knockdown, indirect immunofluorescence, cell fractionation, sucrose gradient centrifugation","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (co-expression reconstitution, Co-IP, knockdown, fractionation, sucrose gradients), focused mechanistic study","pmids":["17353269"],"is_preprint":false},{"year":2005,"finding":"The yeast homologue of WDR12, Ytm1, is present in four consecutive 66S preribosomes and forms a heterotrimeric subcomplex with Erb1 (Bop1 homologue) and Nop7 (Pes1 homologue). Ytm1 binds directly to Erb1; mutations in the WD40 motifs of Ytm1 disrupt Erb1 binding, destabilize the heterotrimer, and delay pre-rRNA processing and nuclear export of preribosomes.","method":"Affinity purification, co-immunoprecipitation, WD40 domain mutagenesis, pre-rRNA processing assays, sucrose gradient sedimentation","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct binding assay with mutagenesis, pre-rRNA processing, and structural domain mapping in focused yeast ortholog study","pmids":["16287855"],"is_preprint":false},{"year":2008,"finding":"In yeast, Ytm1 (WDR12 homologue), Erb1, and Nop7 assemble into preribosomes in an interdependent manner. Specific domains within Ytm1 are necessary for interaction with Erb1 and for recruitment into preribosomes. Overexpression of truncated Ytm1 constructs produces dominant negative effects on growth and ribosome biogenesis, defining interaction and functional domains.","method":"Truncation mutagenesis, dominant-negative overexpression, affinity purification, co-immunoprecipitation, pre-rRNA processing assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — structure-function mutagenesis with multiple truncation alleles, epistatic growth assays, and pre-rRNA processing readouts in yeast ortholog","pmids":["18448671"],"is_preprint":false},{"year":2015,"finding":"The WD40 beta-propeller domains of Erb1 (Bop1) and Ytm1 (WDR12) interact directly via their beta-propeller domains in a high-affinity, novel binding mode. Crystal structure of the Erb1-Ytm1 heterodimer was solved at 2.67 Å. Structure-based interface mutations that impair the Erb1-Ytm1 interaction do not support yeast growth and cause specific defects in 60S subunit synthesis, demonstrating that an intact Erb1-Ytm1 complex is required for 60S maturation.","method":"X-ray crystallography (2.67 Å resolution), structure-based mutagenesis, in vitro binding assays, yeast growth assays, ribosome profiling","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with structure-guided mutagenesis and functional validation in yeast ortholog","pmids":["26657628"],"is_preprint":false},{"year":2015,"finding":"The WD40 beta-propeller domains of Erb1 and Ytm1 (WDR12 ortholog) interact in a novel high-affinity manner. Crystal structure of the C-terminal Erb1-Ytm1 dimer from Chaetomium thermophilum was solved at 2.1 Å. A point mutation within the interface impairs the interaction, negatively affecting growth and ribosome production in yeast.","method":"X-ray crystallography (2.1 Å), in vitro binding assays, yeast genetics, ribosome biogenesis assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis and functional validation in yeast ortholog, independent lab replication of the Thoms et al. 2015 result","pmids":["26476442"],"is_preprint":false},{"year":2015,"finding":"The N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 is bound by the MIDAS domain of midasin (MDN1/Rea1), the AAA-ATPase required for release of the PeBoW/Nop7-Erb1-Ytm1 complex from preribosomal particles. Crystal structure of the yeast Ytm1 UBL domain was solved at 1.7 Å. Human midasin binds WDR12 through its UBL domain; the interaction requires metal ion coordination by the MIDAS domain, as removal of metal ion or mutation of coordinating residues diminishes binding. Mammalian WDR12 nucleolar localization is dependent on active ribosomal RNA transcription.","method":"X-ray crystallography (1.7 Å), in vitro binding assays, MIDAS domain mutagenesis (metal coordination mutants), indirect immunofluorescence, rRNA transcription inhibition","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis of the binding interface, in vitro binding assays, and localization experiment with functional perturbation","pmids":["26601951"],"is_preprint":false},{"year":2002,"finding":"Mouse WDR12 protein was shown to bind in vitro to the cytoplasmic domain of Notch1. WDR12 was predicted to contain seven WD repeat units and a nuclear localization signal. The amino-terminal region shows similarity to the Notchless WD repeat protein.","method":"In vitro binding assay (pull-down), sequence analysis, gene expression studies","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single in vitro pull-down with no functional follow-up; no reciprocal Co-IP or cellular validation","pmids":["11827460"],"is_preprint":false},{"year":2015,"finding":"WDR12 gene delivery into adult rat hearts decreased cellular proliferation, activated the p38 MAPK/HSP27 pathway, and increased BOP1 protein levels, resulting in deterioration of cardiac function (decreased ejection fraction and fractional shortening). WDR12 protein levels were increased in patients with dilated cardiomyopathy and in rats post-infarction.","method":"Adenovirus-mediated gene delivery, echocardiography, western blot, immunohistochemistry","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gain-of-function in vivo with defined phenotypic readouts and pathway activation (p38 MAPK/HSP27, BOP1), single lab","pmids":["25915632"],"is_preprint":false},{"year":2021,"finding":"WDR12 silencing in glioma stem-like cells results in degradation of all PeBoW complex components and prevents maturation of 28S rRNA, thereby inhibiting ribosome biogenesis. WDR12 depletion compromises GSC proliferation and inhibits orthotopic tumor growth in vivo.","method":"shRNA knockdown, rRNA processing assay (28S maturation), western blot for complex component stability, orthotopic xenograft","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular readout (rRNA processing, complex stability) and in vivo validation, single lab","pmids":["34868955"],"is_preprint":false},{"year":2026,"finding":"DR5 competes with p65 for binding to WDR12, a linker protein of the CUL4B-DDB1 E3 ubiquitin ligase complex. By competitively binding WDR12, DR5 reduces ubiquitin-mediated proteasomal degradation of p65, thereby enhancing NF-κB signaling and promoting transcriptional upregulation of DR5 and BCL2 in renal cell carcinoma.","method":"Co-immunoprecipitation, competitive binding assays, gain- and loss-of-function experiments, ubiquitination assays, in vitro and in vivo models","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP competitive binding and ubiquitination assays with gain/loss-of-function, single lab, novel role as CUL4B-DDB1 complex linker","pmids":["41872532"],"is_preprint":false},{"year":2024,"finding":"WDR12 knockdown in colorectal cancer cells downregulates RAC1 expression, which in turn reduces proliferation and promotes apoptosis. mRNA chip-sequencing and IPA after WDR12 knockdown identified activation of cell cycle checkpoint kinase proteins in the checkpoint control signaling pathway.","method":"shRNA knockdown, mRNA chip-sequencing, IPA pathway analysis, cell proliferation and apoptosis assays (Celigo, MTT, Caspase-3/7), in vivo xenograft","journal":"Molecular and cellular biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, gene expression profiling after knockdown without direct protein-protein interaction validation for WDR12-RAC1 relationship","pmids":["38341833"],"is_preprint":false}],"current_model":"WDR12 is a WD40 repeat protein with an N-terminal ubiquitin-like (UBL) domain that functions as an essential component of the trimeric PeBoW complex (with Pes1/Nop7 and Bop1/Erb1), where it is required for 32S/27S pre-rRNA processing and 60S ribosomal subunit maturation; its WD40 domain engages Bop1/Erb1 via a high-affinity beta-propeller–propeller interface (crystal structures available), while its UBL domain is recognized by the AAA-ATPase midasin/MDN1 in a metal-ion-dependent manner to release the PeBoW complex from pre-ribosomal particles, and disruption of PeBoW integrity triggers p53 accumulation and cell cycle arrest; additionally, WDR12 has been identified as a linker subunit of the CUL4B-DDB1 E3 ligase complex that regulates p65 stability via ubiquitin-mediated degradation."},"narrative":{"mechanistic_narrative":"WDR12 is an essential ribosome biogenesis factor that operates as one of three subunits of the trimeric PeBoW complex (with Pes1/Nop7 and Bop1/Erb1), where it is required for processing of the 32S precursor rRNA and maturation of the 60S ribosomal subunit [PMID:16043514, PMID:16287855]. WDR12 incorporates into the complex through a direct, high-affinity interaction between its C-terminal WD40 beta-propeller domain and the beta-propeller of Bop1/Erb1, an interface defined by crystal structures whose disruption abolishes 60S synthesis [PMID:26657628, PMID:26476442]; its nucleolar localization is dependent on this incorporation into PeBoW and on active rRNA transcription [PMID:17353269, PMID:26601951]. Bop1/Erb1 serves as the scaffold of the complex, and the three subunits assemble in an interdependent manner such that loss of WDR12 destabilizes the entire complex and blocks 28S/large-subunit rRNA maturation [PMID:17353269, PMID:34868955]. The N-terminal ubiquitin-like (UBL) domain of WDR12 is recognized by the MIDAS domain of the AAA-ATPase midasin/MDN1 in a metal-ion-dependent manner, the recognition event that releases the PeBoW complex from pre-ribosomal particles [PMID:26601951]. Disruption of PeBoW integrity triggers a nucleolar surveillance response, causing p53 accumulation and reversible cell cycle arrest in proliferating cells [PMID:16043514], and WDR12 depletion impairs proliferation and tumor growth in glioma stem-like cells [PMID:34868955]. Beyond its ribosomal role, WDR12 functions as a linker subunit of the CUL4B-DDB1 E3 ubiquitin ligase complex, promoting ubiquitin-mediated degradation of p65 to restrain NF-κB signaling [PMID:41872532].","teleology":[{"year":2005,"claim":"Established that WDR12 is a dedicated ribosome biogenesis factor by placing it in a stable trimeric complex required for pre-rRNA processing and linking its disruption to a p53-dependent cell cycle checkpoint.","evidence":"Co-IP, dominant-negative expression, rRNA processing and p53 accumulation assays in mammalian cells","pmids":["16043514"],"confidence":"High","gaps":["Did not resolve which subunit nucleates the complex","Mechanism linking PeBoW disruption to p53 accumulation left undefined"]},{"year":2005,"claim":"Identified the yeast ortholog Ytm1 within preribosomes and mapped its direct, WD40-dependent binding to Erb1, establishing the conserved heterotrimeric architecture and its requirement for pre-rRNA processing and preribosome export.","evidence":"Affinity purification, WD40 mutagenesis, pre-rRNA processing and sucrose gradient assays in yeast","pmids":["16287855"],"confidence":"High","gaps":["Structural basis of the WD40-Erb1 interface not yet resolved","Assembly order/interdependence not established"]},{"year":2007,"claim":"Defined Bop1 as the scaffold of PeBoW and showed WDR12's nucleolar localization is contingent on complex incorporation, clarifying the hierarchy of subunit assembly.","evidence":"Recombinant reconstitution, Co-IP, siRNA knockdown, immunofluorescence and sucrose gradients in mammalian cells","pmids":["17353269"],"confidence":"High","gaps":["Atomic detail of subunit contacts unresolved","How WDR12 rescues Bop1 overexpression toxicity not mechanistically explained"]},{"year":2008,"claim":"Demonstrated interdependent assembly of Ytm1/Erb1/Nop7 into preribosomes and delineated the specific Ytm1 domains required for Erb1 interaction and recruitment.","evidence":"Truncation mutagenesis, dominant-negative overexpression, affinity purification and pre-rRNA assays in yeast","pmids":["18448671"],"confidence":"High","gaps":["Interface defined functionally but not structurally","Release mechanism from preribosomes not addressed"]},{"year":2015,"claim":"Resolved the atomic basis of WDR12 incorporation by solving the Erb1-Ytm1 beta-propeller-propeller heterodimer structures and proving interface integrity is required for 60S maturation.","evidence":"X-ray crystallography (2.67 Å and 2.1 Å), structure-based mutagenesis and yeast ribosome biogenesis assays","pmids":["26657628","26476442"],"confidence":"High","gaps":["Does not address how the complex is later removed from preribosomes","Human structural confirmation not provided"]},{"year":2015,"claim":"Identified the WDR12 UBL domain as the substrate recognized by midasin's MIDAS domain in a metal-dependent manner, defining the molecular handle by which the AAA-ATPase releases PeBoW from preribosomes.","evidence":"X-ray crystallography (1.7 Å), in vitro binding with MIDAS metal-coordination mutants, immunofluorescence with rRNA transcription inhibition","pmids":["26601951"],"confidence":"High","gaps":["Energetics/kinetics of the ATP-driven release reaction not characterized","Coupling of UBL recognition to physical extraction not directly visualized"]},{"year":2015,"claim":"Linked WDR12 dosage to a non-ribosomal cardiac phenotype, showing its overexpression impairs cardiac function via p38 MAPK/HSP27 and elevated BOP1.","evidence":"Adenoviral gene delivery, echocardiography, western blot and IHC in rat hearts and patient samples","pmids":["25915632"],"confidence":"Medium","gaps":["Direct molecular target driving p38 activation not identified","Whether the effect requires PeBoW or ribosome biogenesis unresolved"]},{"year":2021,"claim":"Confirmed in human cancer cells that WDR12 is required for PeBoW complex stability and large-subunit rRNA maturation, with depletion suppressing tumor growth.","evidence":"shRNA knockdown, 28S rRNA processing assay, complex stability western blots and orthotopic xenograft in glioma stem-like cells","pmids":["34868955"],"confidence":"Medium","gaps":["Does not separate antitumor effect from general ribosome biogenesis dependence","Single lab"]},{"year":2026,"claim":"Revealed a second, ribosome-independent function for WDR12 as a linker subunit of the CUL4B-DDB1 E3 ligase that targets p65 for degradation, with DR5 competing for binding to derepress NF-κB signaling.","evidence":"Co-IP, competitive binding and ubiquitination assays with gain/loss-of-function in renal cell carcinoma models","pmids":["41872532"],"confidence":"Medium","gaps":["Structural basis of WDR12-DDB1/p65 contacts not defined","Relationship between PeBoW pool and CUL4B-DDB1 pool of WDR12 unclear","Single lab"]},{"year":null,"claim":"It remains unresolved how WDR12 is partitioned between its nucleolar ribosome-biogenesis role and its CUL4B-DDB1 E3-ligase role, and whether the Notch1-binding observation reflects a genuine signaling function.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of WDR12 within CUL4B-DDB1","Notch1 binding (idx 7) never functionally validated","RAC1 regulation (idx 11) lacks direct interaction evidence"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[4,10]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[1,6]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,2,4,9]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,9]}],"complexes":["PeBoW complex (Pes1-Bop1-WDR12)","CUL4B-DDB1 E3 ubiquitin ligase complex"],"partners":["BOP1","PES1","MDN1","DDB1","CUL4B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9GZL7","full_name":"Ribosome biogenesis protein WDR12","aliases":["WD repeat-containing protein 12"],"length_aa":423,"mass_kda":47.7,"function":"Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome","subcellular_location":"Nucleus, nucleolus; Nucleus, nucleoplasm","url":"https://www.uniprot.org/uniprotkb/Q9GZL7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR12","classification":"Common Essential","n_dependent_lines":1191,"n_total_lines":1208,"dependency_fraction":0.9859271523178808},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000138442","cell_line_id":"CID001074","localizations":[{"compartment":"nucleolus_gc","grade":3},{"compartment":"nucleoplasm","grade":1}],"interactors":[{"gene":"PES1","stoichiometry":10.0},{"gene":"BOP1","stoichiometry":10.0},{"gene":"DDX27","stoichiometry":4.0},{"gene":"CSNK2A1","stoichiometry":0.2},{"gene":"CSNK2A2","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"NPM3","stoichiometry":0.2},{"gene":"PPM1G","stoichiometry":0.2},{"gene":"RPL7L1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001074","total_profiled":1310},"omim":[{"mim_id":"616621","title":"DEAD-BOX HELICASE 27; DDX27","url":"https://www.omim.org/entry/616621"},{"mim_id":"616620","title":"WD REPEAT-CONTAINING PROTEIN 12; WDR12","url":"https://www.omim.org/entry/616620"},{"mim_id":"610596","title":"BLOCK OF PROLIFERATION 1; BOP1","url":"https://www.omim.org/entry/610596"},{"mim_id":"605819","title":"PESCADILLO RIBOSOMAL BIOGENESIS FACTOR 1; PES1","url":"https://www.omim.org/entry/605819"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/WDR12"},"hgnc":{"alias_symbol":["YTM1","FLJ10881"],"prev_symbol":[]},"alphafold":{"accession":"Q9GZL7","domains":[{"cath_id":"3.10.20.90","chopping":"2-86","consensus_level":"high","plddt":88.6133,"start":2,"end":86},{"cath_id":"2.130.10.10","chopping":"92-223_238-412","consensus_level":"medium","plddt":93.2167,"start":92,"end":412}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZL7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZL7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZL7-F1-predicted_aligned_error_v6.png","plddt_mean":89.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR12","jax_strain_url":"https://www.jax.org/strain/search?query=WDR12"},"sequence":{"accession":"Q9GZL7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9GZL7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9GZL7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZL7"}},"corpus_meta":[{"pmid":"16043514","id":"PMC_16043514","title":"Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation.","date":"2005","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/16043514","citation_count":165,"is_preprint":false},{"pmid":"17353269","id":"PMC_17353269","title":"Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit.","date":"2007","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353269","citation_count":112,"is_preprint":false},{"pmid":"16287855","id":"PMC_16287855","title":"Ytm1, Nop7, and Erb1 form a complex necessary for maturation of yeast 66S preribosomes.","date":"2005","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16287855","citation_count":84,"is_preprint":false},{"pmid":"18448671","id":"PMC_18448671","title":"Interactions among Ytm1, Erb1, and Nop7 required for assembly of the Nop7-subcomplex in yeast preribosomes.","date":"2008","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18448671","citation_count":50,"is_preprint":false},{"pmid":"26657628","id":"PMC_26657628","title":"Concerted removal of the Erb1-Ytm1 complex in ribosome biogenesis relies on an elaborate interface.","date":"2015","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/26657628","citation_count":28,"is_preprint":false},{"pmid":"26601951","id":"PMC_26601951","title":"The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26601951","citation_count":27,"is_preprint":false},{"pmid":"11827460","id":"PMC_11827460","title":"Wdr12, a mouse gene encoding a novel WD-Repeat Protein with a notchless-like amino-terminal domain.","date":"2002","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/11827460","citation_count":21,"is_preprint":false},{"pmid":"26476442","id":"PMC_26476442","title":"The structure of Erb1-Ytm1 complex reveals the functional importance of a high-affinity binding between two β-propellers during the assembly of large ribosomal subunits in eukaryotes.","date":"2015","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/26476442","citation_count":18,"is_preprint":false},{"pmid":"30310320","id":"PMC_30310320","title":"Identification of WDR12 as a novel oncogene involved in hepatocellular carcinoma propagation.","date":"2018","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/30310320","citation_count":17,"is_preprint":false},{"pmid":"32180229","id":"PMC_32180229","title":"Integrative genomic analyses identify WDR12 as a novel oncogene involved in glioblastoma.","date":"2020","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32180229","citation_count":16,"is_preprint":false},{"pmid":"38795544","id":"PMC_38795544","title":"circMIRIAF aggravates myocardial ischemia-reperfusion injury via targeting miR-544/WDR12 axis.","date":"2024","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/38795544","citation_count":14,"is_preprint":false},{"pmid":"34868955","id":"PMC_34868955","title":"Suppression of Ribosome Biogenesis by Targeting WD Repeat Domain 12 (WDR12) Inhibits Glioma Stem-Like Cell Growth.","date":"2021","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/34868955","citation_count":12,"is_preprint":false},{"pmid":"38341833","id":"PMC_38341833","title":"WDR12/RAC1 axis promoted proliferation and anti-apoptosis in colorectal cancer cells.","date":"2024","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38341833","citation_count":9,"is_preprint":false},{"pmid":"36178131","id":"PMC_36178131","title":"Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm.","date":"2023","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/36178131","citation_count":9,"is_preprint":false},{"pmid":"25915632","id":"PMC_25915632","title":"WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25915632","citation_count":8,"is_preprint":false},{"pmid":"33488114","id":"PMC_33488114","title":"Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity.","date":"2021","source":"International journal of general medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33488114","citation_count":6,"is_preprint":false},{"pmid":"34540895","id":"PMC_34540895","title":"Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors.","date":"2021","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/34540895","citation_count":1,"is_preprint":false},{"pmid":"39969382","id":"PMC_39969382","title":"Roles of WDR12 and MRTO4 genes in colorectal cancer.","date":"2024","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39969382","citation_count":0,"is_preprint":false},{"pmid":"41872532","id":"PMC_41872532","title":"DR5/WDR12 balances p65 stability promoting sunitinib resistance in renal cell carcinoma.","date":"2026","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/41872532","citation_count":0,"is_preprint":false},{"pmid":"41894147","id":"PMC_41894147","title":"WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers.","date":"2026","source":"Alzheimer's & dementia : the journal of the Alzheimer's Association","url":"https://pubmed.ncbi.nlm.nih.gov/41894147","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12060,"output_tokens":3431,"usd":0.043823,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10908,"output_tokens":3328,"usd":0.06887,"stage2_stop_reason":"end_turn"},"total_usd":0.112693,"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\": 2005,\n      \"finding\": \"WDR12 forms a stable trimeric complex with Pes1 and Bop1 (PeBoW complex) in mammalian cells. WDR12 is required for processing of the 32S precursor rRNA. A dominant-negative mutant of WDR12 blocks rRNA processing and induces reversible cell cycle arrest, triggering p53 accumulation in a p19ARF-independent manner in proliferating but not quiescent cells.\",\n      \"method\": \"Co-immunoprecipitation, dominant-negative expression, cell fractionation, rRNA processing assays, p53 accumulation assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, dominant-negative mutagenesis, rRNA processing assays, and p53 pathway placement in a focused mechanistic study; replicated in subsequent work\",\n      \"pmids\": [\"16043514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Bop1 is the integral scaffold of the PeBoW complex: knockdown of Bop1 abolishes copurification of Pes1 with WDR12, while recombinant expression of all three subunits (Pes1, Bop1, WDR12) is sufficient for complex formation. WDR12 nucleolar localization depends on its incorporation into the PeBoW complex. Overexpression of Bop1 inhibits cell proliferation and rRNA processing, and coexpression of WDR12 (but not Pes1) rescues these negative effects.\",\n      \"method\": \"Recombinant co-expression, Co-immunoprecipitation, siRNA knockdown, indirect immunofluorescence, cell fractionation, sucrose gradient centrifugation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (co-expression reconstitution, Co-IP, knockdown, fractionation, sucrose gradients), focused mechanistic study\",\n      \"pmids\": [\"17353269\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The yeast homologue of WDR12, Ytm1, is present in four consecutive 66S preribosomes and forms a heterotrimeric subcomplex with Erb1 (Bop1 homologue) and Nop7 (Pes1 homologue). Ytm1 binds directly to Erb1; mutations in the WD40 motifs of Ytm1 disrupt Erb1 binding, destabilize the heterotrimer, and delay pre-rRNA processing and nuclear export of preribosomes.\",\n      \"method\": \"Affinity purification, co-immunoprecipitation, WD40 domain mutagenesis, pre-rRNA processing assays, sucrose gradient sedimentation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct binding assay with mutagenesis, pre-rRNA processing, and structural domain mapping in focused yeast ortholog study\",\n      \"pmids\": [\"16287855\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"In yeast, Ytm1 (WDR12 homologue), Erb1, and Nop7 assemble into preribosomes in an interdependent manner. Specific domains within Ytm1 are necessary for interaction with Erb1 and for recruitment into preribosomes. Overexpression of truncated Ytm1 constructs produces dominant negative effects on growth and ribosome biogenesis, defining interaction and functional domains.\",\n      \"method\": \"Truncation mutagenesis, dominant-negative overexpression, affinity purification, co-immunoprecipitation, pre-rRNA processing assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — structure-function mutagenesis with multiple truncation alleles, epistatic growth assays, and pre-rRNA processing readouts in yeast ortholog\",\n      \"pmids\": [\"18448671\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The WD40 beta-propeller domains of Erb1 (Bop1) and Ytm1 (WDR12) interact directly via their beta-propeller domains in a high-affinity, novel binding mode. Crystal structure of the Erb1-Ytm1 heterodimer was solved at 2.67 Å. Structure-based interface mutations that impair the Erb1-Ytm1 interaction do not support yeast growth and cause specific defects in 60S subunit synthesis, demonstrating that an intact Erb1-Ytm1 complex is required for 60S maturation.\",\n      \"method\": \"X-ray crystallography (2.67 Å resolution), structure-based mutagenesis, in vitro binding assays, yeast growth assays, ribosome profiling\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with structure-guided mutagenesis and functional validation in yeast ortholog\",\n      \"pmids\": [\"26657628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The WD40 beta-propeller domains of Erb1 and Ytm1 (WDR12 ortholog) interact in a novel high-affinity manner. Crystal structure of the C-terminal Erb1-Ytm1 dimer from Chaetomium thermophilum was solved at 2.1 Å. A point mutation within the interface impairs the interaction, negatively affecting growth and ribosome production in yeast.\",\n      \"method\": \"X-ray crystallography (2.1 Å), in vitro binding assays, yeast genetics, ribosome biogenesis assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis and functional validation in yeast ortholog, independent lab replication of the Thoms et al. 2015 result\",\n      \"pmids\": [\"26476442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 is bound by the MIDAS domain of midasin (MDN1/Rea1), the AAA-ATPase required for release of the PeBoW/Nop7-Erb1-Ytm1 complex from preribosomal particles. Crystal structure of the yeast Ytm1 UBL domain was solved at 1.7 Å. Human midasin binds WDR12 through its UBL domain; the interaction requires metal ion coordination by the MIDAS domain, as removal of metal ion or mutation of coordinating residues diminishes binding. Mammalian WDR12 nucleolar localization is dependent on active ribosomal RNA transcription.\",\n      \"method\": \"X-ray crystallography (1.7 Å), in vitro binding assays, MIDAS domain mutagenesis (metal coordination mutants), indirect immunofluorescence, rRNA transcription inhibition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis of the binding interface, in vitro binding assays, and localization experiment with functional perturbation\",\n      \"pmids\": [\"26601951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Mouse WDR12 protein was shown to bind in vitro to the cytoplasmic domain of Notch1. WDR12 was predicted to contain seven WD repeat units and a nuclear localization signal. The amino-terminal region shows similarity to the Notchless WD repeat protein.\",\n      \"method\": \"In vitro binding assay (pull-down), sequence analysis, gene expression studies\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single in vitro pull-down with no functional follow-up; no reciprocal Co-IP or cellular validation\",\n      \"pmids\": [\"11827460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"WDR12 gene delivery into adult rat hearts decreased cellular proliferation, activated the p38 MAPK/HSP27 pathway, and increased BOP1 protein levels, resulting in deterioration of cardiac function (decreased ejection fraction and fractional shortening). WDR12 protein levels were increased in patients with dilated cardiomyopathy and in rats post-infarction.\",\n      \"method\": \"Adenovirus-mediated gene delivery, echocardiography, western blot, immunohistochemistry\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gain-of-function in vivo with defined phenotypic readouts and pathway activation (p38 MAPK/HSP27, BOP1), single lab\",\n      \"pmids\": [\"25915632\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"WDR12 silencing in glioma stem-like cells results in degradation of all PeBoW complex components and prevents maturation of 28S rRNA, thereby inhibiting ribosome biogenesis. WDR12 depletion compromises GSC proliferation and inhibits orthotopic tumor growth in vivo.\",\n      \"method\": \"shRNA knockdown, rRNA processing assay (28S maturation), western blot for complex component stability, orthotopic xenograft\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular readout (rRNA processing, complex stability) and in vivo validation, single lab\",\n      \"pmids\": [\"34868955\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"DR5 competes with p65 for binding to WDR12, a linker protein of the CUL4B-DDB1 E3 ubiquitin ligase complex. By competitively binding WDR12, DR5 reduces ubiquitin-mediated proteasomal degradation of p65, thereby enhancing NF-κB signaling and promoting transcriptional upregulation of DR5 and BCL2 in renal cell carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, competitive binding assays, gain- and loss-of-function experiments, ubiquitination assays, in vitro and in vivo models\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP competitive binding and ubiquitination assays with gain/loss-of-function, single lab, novel role as CUL4B-DDB1 complex linker\",\n      \"pmids\": [\"41872532\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"WDR12 knockdown in colorectal cancer cells downregulates RAC1 expression, which in turn reduces proliferation and promotes apoptosis. mRNA chip-sequencing and IPA after WDR12 knockdown identified activation of cell cycle checkpoint kinase proteins in the checkpoint control signaling pathway.\",\n      \"method\": \"shRNA knockdown, mRNA chip-sequencing, IPA pathway analysis, cell proliferation and apoptosis assays (Celigo, MTT, Caspase-3/7), in vivo xenograft\",\n      \"journal\": \"Molecular and cellular biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, gene expression profiling after knockdown without direct protein-protein interaction validation for WDR12-RAC1 relationship\",\n      \"pmids\": [\"38341833\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR12 is a WD40 repeat protein with an N-terminal ubiquitin-like (UBL) domain that functions as an essential component of the trimeric PeBoW complex (with Pes1/Nop7 and Bop1/Erb1), where it is required for 32S/27S pre-rRNA processing and 60S ribosomal subunit maturation; its WD40 domain engages Bop1/Erb1 via a high-affinity beta-propeller–propeller interface (crystal structures available), while its UBL domain is recognized by the AAA-ATPase midasin/MDN1 in a metal-ion-dependent manner to release the PeBoW complex from pre-ribosomal particles, and disruption of PeBoW integrity triggers p53 accumulation and cell cycle arrest; additionally, WDR12 has been identified as a linker subunit of the CUL4B-DDB1 E3 ligase complex that regulates p65 stability via ubiquitin-mediated degradation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR12 is an essential ribosome biogenesis factor that operates as one of three subunits of the trimeric PeBoW complex (with Pes1/Nop7 and Bop1/Erb1), where it is required for processing of the 32S precursor rRNA and maturation of the 60S ribosomal subunit [#0, #2]. WDR12 incorporates into the complex through a direct, high-affinity interaction between its C-terminal WD40 beta-propeller domain and the beta-propeller of Bop1/Erb1, an interface defined by crystal structures whose disruption abolishes 60S synthesis [#4, #5]; its nucleolar localization is dependent on this incorporation into PeBoW and on active rRNA transcription [#1, #6]. Bop1/Erb1 serves as the scaffold of the complex, and the three subunits assemble in an interdependent manner such that loss of WDR12 destabilizes the entire complex and blocks 28S/large-subunit rRNA maturation [#1, #9]. The N-terminal ubiquitin-like (UBL) domain of WDR12 is recognized by the MIDAS domain of the AAA-ATPase midasin/MDN1 in a metal-ion-dependent manner, the recognition event that releases the PeBoW complex from pre-ribosomal particles [#6]. Disruption of PeBoW integrity triggers a nucleolar surveillance response, causing p53 accumulation and reversible cell cycle arrest in proliferating cells [#0], and WDR12 depletion impairs proliferation and tumor growth in glioma stem-like cells [#9]. Beyond its ribosomal role, WDR12 functions as a linker subunit of the CUL4B-DDB1 E3 ubiquitin ligase complex, promoting ubiquitin-mediated degradation of p65 to restrain NF-\\u03baB signaling [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established that WDR12 is a dedicated ribosome biogenesis factor by placing it in a stable trimeric complex required for pre-rRNA processing and linking its disruption to a p53-dependent cell cycle checkpoint.\",\n      \"evidence\": \"Co-IP, dominant-negative expression, rRNA processing and p53 accumulation assays in mammalian cells\",\n      \"pmids\": [\"16043514\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which subunit nucleates the complex\", \"Mechanism linking PeBoW disruption to p53 accumulation left undefined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified the yeast ortholog Ytm1 within preribosomes and mapped its direct, WD40-dependent binding to Erb1, establishing the conserved heterotrimeric architecture and its requirement for pre-rRNA processing and preribosome export.\",\n      \"evidence\": \"Affinity purification, WD40 mutagenesis, pre-rRNA processing and sucrose gradient assays in yeast\",\n      \"pmids\": [\"16287855\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the WD40-Erb1 interface not yet resolved\", \"Assembly order/interdependence not established\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined Bop1 as the scaffold of PeBoW and showed WDR12's nucleolar localization is contingent on complex incorporation, clarifying the hierarchy of subunit assembly.\",\n      \"evidence\": \"Recombinant reconstitution, Co-IP, siRNA knockdown, immunofluorescence and sucrose gradients in mammalian cells\",\n      \"pmids\": [\"17353269\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic detail of subunit contacts unresolved\", \"How WDR12 rescues Bop1 overexpression toxicity not mechanistically explained\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrated interdependent assembly of Ytm1/Erb1/Nop7 into preribosomes and delineated the specific Ytm1 domains required for Erb1 interaction and recruitment.\",\n      \"evidence\": \"Truncation mutagenesis, dominant-negative overexpression, affinity purification and pre-rRNA assays in yeast\",\n      \"pmids\": [\"18448671\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Interface defined functionally but not structurally\", \"Release mechanism from preribosomes not addressed\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Resolved the atomic basis of WDR12 incorporation by solving the Erb1-Ytm1 beta-propeller-propeller heterodimer structures and proving interface integrity is required for 60S maturation.\",\n      \"evidence\": \"X-ray crystallography (2.67 \\u00c5 and 2.1 \\u00c5), structure-based mutagenesis and yeast ribosome biogenesis assays\",\n      \"pmids\": [\"26657628\", \"26476442\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address how the complex is later removed from preribosomes\", \"Human structural confirmation not provided\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified the WDR12 UBL domain as the substrate recognized by midasin's MIDAS domain in a metal-dependent manner, defining the molecular handle by which the AAA-ATPase releases PeBoW from preribosomes.\",\n      \"evidence\": \"X-ray crystallography (1.7 \\u00c5), in vitro binding with MIDAS metal-coordination mutants, immunofluorescence with rRNA transcription inhibition\",\n      \"pmids\": [\"26601951\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Energetics/kinetics of the ATP-driven release reaction not characterized\", \"Coupling of UBL recognition to physical extraction not directly visualized\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Linked WDR12 dosage to a non-ribosomal cardiac phenotype, showing its overexpression impairs cardiac function via p38 MAPK/HSP27 and elevated BOP1.\",\n      \"evidence\": \"Adenoviral gene delivery, echocardiography, western blot and IHC in rat hearts and patient samples\",\n      \"pmids\": [\"25915632\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular target driving p38 activation not identified\", \"Whether the effect requires PeBoW or ribosome biogenesis unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Confirmed in human cancer cells that WDR12 is required for PeBoW complex stability and large-subunit rRNA maturation, with depletion suppressing tumor growth.\",\n      \"evidence\": \"shRNA knockdown, 28S rRNA processing assay, complex stability western blots and orthotopic xenograft in glioma stem-like cells\",\n      \"pmids\": [\"34868955\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not separate antitumor effect from general ribosome biogenesis dependence\", \"Single lab\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Revealed a second, ribosome-independent function for WDR12 as a linker subunit of the CUL4B-DDB1 E3 ligase that targets p65 for degradation, with DR5 competing for binding to derepress NF-\\u03baB signaling.\",\n      \"evidence\": \"Co-IP, competitive binding and ubiquitination assays with gain/loss-of-function in renal cell carcinoma models\",\n      \"pmids\": [\"41872532\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of WDR12-DDB1/p65 contacts not defined\", \"Relationship between PeBoW pool and CUL4B-DDB1 pool of WDR12 unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how WDR12 is partitioned between its nucleolar ribosome-biogenesis role and its CUL4B-DDB1 E3-ligase role, and whether the Notch1-binding observation reflects a genuine signaling function.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of WDR12 within CUL4B-DDB1\", \"Notch1 binding (idx 7) never functionally validated\", \"RAC1 regulation (idx 11) lacks direct interaction evidence\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [4, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [1, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 2, 4, 9]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"complexes\": [\"PeBoW complex (Pes1-Bop1-WDR12)\", \"CUL4B-DDB1 E3 ubiquitin ligase complex\"],\n    \"partners\": [\"BOP1\", \"PES1\", \"MDN1\", \"DDB1\", \"CUL4B\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}