{"gene":"DDX10","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":1996,"finding":"DDX10 encodes a putative DEAD-box RNA helicase with predicted involvement in ribosome biogenesis, based on high sequence similarity to DEAD-box RNA helicases involved in ribosome biogenesis.","method":"Positional cloning, sequence analysis","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence prediction only, no direct functional assay","pmids":["8660968"],"is_preprint":false},{"year":1997,"finding":"Inversion 11(p15q22) fuses NUP98 (nucleoporin) in-frame with DDX10 (putative RNA helicase) to produce the NUP98-DDX10 chimeric transcript; only the NUP98-DDX10 direction (not DDX10-NUP98) appears implicated in tumorigenesis.","method":"Positional cloning, RT-PCR, molecular characterization of translocation breakpoints in four patients","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal fusion characterized by molecular cloning, replicated across four patients and multiple subsequent studies","pmids":["9166830"],"is_preprint":false},{"year":2009,"finding":"Human DDX10 (ortholog of yeast Dbp4) is a component of a novel 50S U3 snoRNP assembly intermediate of the SSU processome; this complex accumulated when pre-rRNA transcription was blocked or tUTP proteins were depleted, and DDX10 was associated with the RNA-binding proteins nucleolin and RRP5 in this intermediate.","method":"Sucrose gradient sedimentation, co-immunoprecipitation, depletion experiments","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and depletion experiments in single lab with multiple orthogonal approaches","pmids":["19332556"],"is_preprint":false},{"year":2010,"finding":"The conserved helicase motif YIHRAGRTAR in DDX10 (required for ATP binding, RNA binding, and helicase function) is required for the in vitro transforming ability of NUP98-DDX10; mutation of this motif diminishes leukemogenic transformation of CD34+ cells.","method":"Site-directed mutagenesis of helicase motif, transformation assay of primary human CD34+ cells, nuclear localization assay","journal":"Leukemia","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — active-site mutagenesis with functional transformation readout, single lab","pmids":["20339440"],"is_preprint":false},{"year":2013,"finding":"Yeast Dbp4 (DDX10 ortholog) interacts with nucleolar proteins Bfr2 and Enp2 in two distinct complexes: a 50S complex (not containing U3 snoRNA but containing U14 snoRNA associated with Dbp4) and an 80S SSU processome (containing U3 snoRNA); Bfr2 and Enp2 are required for early 18S rRNA processing steps.","method":"Sucrose gradient sedimentation, co-immunoprecipitation, northern blotting, genetic depletion","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (co-IP, sedimentation, northern blot), single lab","pmids":["24357410"],"is_preprint":false},{"year":2014,"finding":"Yeast Dbp4 (DDX10 ortholog) is required for SSU processome formation and cotranscriptional pre-rRNA cleavage: depletion of Dbp4 impairs early pre-rRNA cleavage, causes U14 snoRNA to remain associated with pre-rRNA, compromises SSU processome formation visible by electron microscopy, and its C-terminal extension (outside the catalytic core) is required for U14 snoRNA release from pre-rRNA. Dbp4 associates with U3 snoRNA and the U3-specific protein Mpp10 in whole-cell extracts but does not associate with U14 snoRNA.","method":"Immunoprecipitation, electron microscopy, sucrose density gradient analysis, genetic depletion, domain truncation analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods including EM, co-IP, sedimentation, and domain truncation in one study; findings consistent with prior work in same field","pmids":["25535329"],"is_preprint":false},{"year":2021,"finding":"DDX10 (and yeast ortholog Dbp4) physically interacts with α-synuclein; α-synuclein sequesters DDX10 outside the nucleolus in both yeast and human cells, and this interaction stabilizes a fraction of α-synuclein oligomeric species. Downregulation of DBP4/DDX10 rescues cells from α-synuclein toxicity, while overexpression produces a synthetic lethal phenotype.","method":"Yeast genetic screen, co-immunoprecipitation, fluorescence microscopy (localization), genetic overexpression/knockdown with growth/toxicity readouts","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, live imaging, and genetic epistasis in single lab with orthogonal methods","pmids":["33657088"],"is_preprint":false},{"year":2021,"finding":"DDX10 knockdown in lung cancer cells inhibits proliferation in vitro and in vivo; DDX10 positively correlates with the U3 snoRNP component IMP4, and IMP4 overexpression rescues the anti-proliferative effect of DDX10 knockdown, placing IMP4 downstream of DDX10.","method":"shRNA knockdown, in vitro proliferation assay, xenograft (in vivo), rescue experiment with IMP4 overexpression","journal":"Thoracic cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via rescue experiment, in vitro and in vivo, single lab","pmids":["33973712"],"is_preprint":false},{"year":2020,"finding":"DDX10 promotes AIM2 inflammasome activation by interacting with the HIN-200 domain of AIM2 and stabilizing AIM2 protein expression; DDX10 knockout in THP-1 macrophages inhibits AIM2 inflammasome activation (reduced caspase-1 cleavage and IL-1β release), and DDX10 co-localizes with AIM2 in HEK293T cells.","method":"Co-immunoprecipitation, ELISA (IL-1β), Western blot (caspase-1 cleavage), CRISPR knockout, immunofluorescence/confocal microscopy","journal":"Xi bao yu fen zi mian yi xue za zhi","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP identifying domain of interaction, KO with functional readout, co-localization, single lab","pmids":["32519665"],"is_preprint":false},{"year":2022,"finding":"DDX10 interacts with RPL35 (identified by LC-MS/MS and confirmed by co-immunoprecipitation) and is linked to RNA splicing and E2F targets in colorectal cancer cells; DDX10 knockdown reduces CRC cell proliferation, migration, and invasion.","method":"LC-MS/MS proteomics, co-immunoprecipitation, shRNA knockdown, cell proliferation/migration/invasion assays, in vivo xenograft","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — binding partner identified by MS and confirmed by co-IP, functional KD phenotype, single lab","pmids":["35109823"],"is_preprint":false},{"year":2023,"finding":"PRRSV infection promotes DDX10 translocation from the nucleus to the cytoplasm for autophagic degradation. The viral envelope (E) protein interacts with DDX10, induces autophagy, and reduces DDX10 protein levels in wild-type cells but not in ATG5 or ATG7 KO cells. SQSTM1/p62 cargo receptor interacts with both DDX10 and E protein and mediates selective autophagic degradation of DDX10. DDX10 positively regulates type I interferon production, contributing to its antiviral effect against PRRSV.","method":"Co-immunoprecipitation, CRISPR knockout (ATG5, ATG7, SQSTM1), fluorescence microscopy (nuclear-cytoplasmic translocation), ectopic expression, siRNA knockdown, interferon reporter assays","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple KO cell lines, co-IP, mechanistic pathway dissection with multiple orthogonal methods in single rigorous study","pmids":["36779599"],"is_preprint":false},{"year":2024,"finding":"DDX10 deletion in colorectal cancer cells increases ATG10 expression and activates autophagy; inhibition of ATG10 or treatment with the autophagy inhibitor 3-MA partially rescues the anti-proliferative and pro-apoptotic effects of DDX10 silencing, placing ATG10-dependent autophagy downstream of DDX10 in CRC cell regulation.","method":"siRNA knockdown, autophagy inhibitor (3-MA), Western blot, EDU staining (proliferation), TUNEL (apoptosis), sphere formation assay","journal":"Journal of cancer research and clinical oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via rescue with ATG10 depletion/inhibitor, multiple readouts, single lab","pmids":["39110225"],"is_preprint":false},{"year":2025,"finding":"Twenty-four amino acids within the DDX10 moiety of NUP98::DDX10 are required for cell immortalization and leukemogenesis; NOL10 (nucleolar protein 10) interacts with these 24 amino acids and is a critical dependency of NUP98::DDX10 leukemia. NOL10 acts cooperatively with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA; loss of Nol10 in a mouse model impairs NUP98::DDX10 leukemia progression.","method":"Domain mapping/mutagenesis, co-immunoprecipitation, mouse leukemia model with Nol10 knockout, mRNA stability assay, metabolic pathway analysis","journal":"Leukemia","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — domain mutagenesis, binding partner identification, in vivo mouse model, and metabolic pathway analysis in one study","pmids":["40263434"],"is_preprint":false},{"year":2025,"finding":"DDX10 physically interacts with Rab27b via phase separation and promotes Rab27b-mediated exosome secretion and PD-L1 loading into exosomes in oral squamous cell carcinoma; DDX10 knockdown inhibits exosomal PD-L1 secretion and restores T cell function and infiltration.","method":"Co-immunoprecipitation (phase separation assay), siRNA knockdown, exosome isolation, flow cytometry/immunofluorescence, T cell functional assays","journal":"Research (Washington, D.C.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP demonstrating phase separation interaction, functional KD with multiple readouts, single lab","pmids":["40352946"],"is_preprint":false},{"year":2025,"finding":"DDX10 binds to fibrillarin (FBL) in DLBCL cells (confirmed by RNA immunoprecipitation); DDX10 and FBL positively regulate each other, and silencing either suppresses DLBCL cell viability, proliferation, invasion, and downregulates β-catenin, cyclin D1, and c-Myc (Wnt/β-catenin pathway components).","method":"RNA immunoprecipitation, siRNA knockdown, cell viability/invasion assays, Western blot (Wnt pathway proteins)","journal":"Molecular and cellular probes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP confirms interaction, functional KD with pathway readout, single lab","pmids":["41338403"],"is_preprint":false}],"current_model":"DDX10 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis by promoting SSU processome formation, facilitating early pre-rRNA cleavage, and mediating release of U14 snoRNA from pre-rRNA via its C-terminal extension; it participates in antiviral innate immunity by positively regulating type I interferon production (and is degraded via SQSTM1-mediated selective autophagy during PRRSV infection); it interacts with AIM2 to stabilize it and promote inflammasome activation; it physically associates with α-synuclein (sequestering DDX10 from the nucleolus and stabilizing α-synuclein oligomers); and in the oncogenic NUP98::DDX10 fusion, a conserved helicase motif and interaction with NOL10 (which co-regulates serine biosynthesis and ATF4 mRNA stability) are required for leukemogenic transformation."},"narrative":{"mechanistic_narrative":"DDX10 is a nucleolar DEAD-box RNA helicase that functions in small-subunit (SSU) ribosome biogenesis, where it (and its yeast ortholog Dbp4) is a component of U3 snoRNP/SSU processome assembly intermediates and associates with nucleolin, RRP5, and the U3-specific protein Mpp10 [PMID:19332556, PMID:25535329]. DDX10 is required for SSU processome formation and cotranscriptional pre-rRNA cleavage; its depletion impairs early pre-rRNA processing and traps U14 snoRNA on pre-rRNA, and its C-terminal extension outside the catalytic core mediates U14 snoRNA release [PMID:25535329]. Beyond ribosome assembly, DDX10 positively regulates type I interferon production and acts as an antiviral factor, and during PRRSV infection it is translocated to the cytoplasm and degraded through SQSTM1/p62-mediated selective autophagy driven by the viral E protein [PMID:36779599]; it also promotes AIM2 inflammasome activation by binding the HIN-200 domain of AIM2 and stabilizing AIM2 protein [PMID:32519665]. DDX10 supports proliferation across several cancers and physically engages partners including IMP4, RPL35, fibrillarin, and Rab27b in these contexts [PMID:33973712, PMID:35109823, PMID:41338403, PMID:40352946]. The t(11;p15q22) inversion fuses NUP98 in-frame with DDX10, and the conserved YIHRAGRTAR helicase motif together with a 24-amino-acid segment that recruits NOL10 — a cooperating regulator of serine biosynthesis and ATF4 mRNA stability — is required for leukemogenic transformation [PMID:9166830, PMID:20339440, PMID:40263434]. DDX10 additionally interacts with α-synuclein, which sequesters it from the nucleolus and stabilizes α-synuclein oligomers [PMID:33657088].","teleology":[{"year":1996,"claim":"Established DDX10 as a candidate DEAD-box RNA helicase, framing a hypothesis that it acts in ribosome biogenesis before any functional assay existed.","evidence":"positional cloning and sequence analysis","pmids":["8660968"],"confidence":"Low","gaps":["sequence prediction only, no functional assay","no localization or substrate data","helicase activity not demonstrated"]},{"year":1997,"claim":"Showed DDX10 is recurrently fused to NUP98 by chromosomal inversion, defining its first disease association and pointing to an oncogenic gain-of-function specifically in the NUP98-DDX10 orientation.","evidence":"RT-PCR and breakpoint cloning across four leukemia patients","pmids":["9166830"],"confidence":"High","gaps":["mechanism of transformation not defined","did not test which DDX10 domains are required","no normal cellular function established"]},{"year":2009,"claim":"Placed human DDX10 in a defined 50S U3 snoRNP SSU-processome assembly intermediate, providing the first physical evidence for its predicted ribosome biogenesis role.","evidence":"sucrose gradient sedimentation, co-IP, and depletion in human cells","pmids":["19332556"],"confidence":"Medium","gaps":["catalytic activity not demonstrated","no rRNA processing readout in human cells","function of nucleolin/RRP5 association unresolved"]},{"year":2010,"claim":"Demonstrated that the conserved helicase motif of DDX10 is required for NUP98-DDX10 transformation, linking the enzyme's ATP/RNA-binding function to leukemogenesis.","evidence":"site-directed mutagenesis and CD34+ cell transformation assays","pmids":["20339440"],"confidence":"Medium","gaps":["RNA substrate of the fusion not identified","downstream target genes undefined","single lab"]},{"year":2014,"claim":"Defined the mechanistic step DDX10/Dbp4 catalyzes: SSU processome formation and cotranscriptional pre-rRNA cleavage, with the C-terminal extension required for U14 snoRNA release.","evidence":"immunoprecipitation, electron microscopy, sedimentation, and domain truncation in yeast","pmids":["25535329","24357410"],"confidence":"High","gaps":["human enzyme not directly assayed for U14 release","ATP-dependent unwinding not reconstituted in vitro","structural basis unknown"]},{"year":2020,"claim":"Extended DDX10 function beyond the nucleolus into innate immunity by showing it stabilizes AIM2 and is required for inflammasome activation.","evidence":"co-IP domain mapping, CRISPR knockout in THP-1, and IL-1β/caspase-1 readouts","pmids":["32519665"],"confidence":"Medium","gaps":["mechanism of AIM2 stabilization unknown","whether helicase activity is required not tested","single lab"]},{"year":2021,"claim":"Connected DDX10 to disease beyond cancer and to proliferation control, showing it sequesters/stabilizes α-synuclein oligomers and that IMP4 acts downstream in lung cancer growth.","evidence":"yeast genetic screen, co-IP, microscopy, and IMP4 rescue in lung cancer cells","pmids":["33657088","33973712"],"confidence":"Medium","gaps":["physiological relevance of α-synuclein interaction in neurons untested","how IMP4 mediates the growth effect unresolved","single labs"]},{"year":2023,"claim":"Defined a regulated degradation pathway for DDX10 and assigned it a positive role in type I interferon production, establishing it as an antiviral host factor targeted by virus.","evidence":"co-IP, ATG5/ATG7/SQSTM1 knockouts, translocation imaging, and IFN reporter assays during PRRSV infection","pmids":["36779599"],"confidence":"High","gaps":["molecular step by which DDX10 promotes IFN unknown","whether RNA helicase activity is required for IFN role untested","human relevance beyond PRRSV model unclear"]},{"year":2022,"claim":"Identified additional cancer-context partners and downstream programs, linking DDX10 to RPL35 and to autophagy regulation in colorectal cancer.","evidence":"LC-MS/MS, co-IP, siRNA knockdown with proliferation/apoptosis readouts and ATG10 epistasis","pmids":["35109823","39110225"],"confidence":"Medium","gaps":["whether DDX10 directly regulates ATG10 unknown","mechanism linking RPL35 binding to phenotype unclear","single labs"]},{"year":2025,"claim":"Resolved the cooperating dependency of the NUP98::DDX10 fusion, showing a 24-residue DDX10 segment recruits NOL10 to drive serine biosynthesis and ATF4 mRNA stability required for leukemia.","evidence":"domain mutagenesis, co-IP, Nol10-knockout mouse leukemia model, and metabolic/mRNA stability assays","pmids":["40263434"],"confidence":"High","gaps":["how NOL10 reprograms serine metabolism mechanistically unresolved","whether NOL10 dependency applies to other NUP98 fusions untested","role of normal DDX10-NOL10 interaction unclear"]},{"year":2025,"claim":"Broadened DDX10's cytoplasmic and tumor-immune roles, implicating it in Rab27b-mediated exosomal PD-L1 secretion and in fibrillarin-coupled Wnt/β-catenin signaling.","evidence":"co-IP/phase separation assay, RNA immunoprecipitation, knockdown with exosome, T cell, and Wnt-pathway readouts","pmids":["40352946","41338403"],"confidence":"Medium","gaps":["how a nucleolar helicase engages cytoplasmic exosome machinery unresolved","directness of Wnt pathway regulation unclear","single labs"]},{"year":null,"claim":"It remains unknown whether DDX10's diverse functions across ribosome biogenesis, innate immunity, autophagy, and cancer share a common biochemical activity, and whether its ATP-dependent RNA unwinding is required outside the SSU processome.","evidence":"no single study reconciles the nucleolar and extranucleolar roles","pmids":[],"confidence":"Low","gaps":["no in vitro reconstitution of human DDX10 helicase activity","RNA substrates in immune and cancer contexts unidentified","structural basis of partner selectivity unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2,5]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[5]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[3,5]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[2,5,6]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3,10]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[2,5]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[5]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[8,10]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,3,12]}],"complexes":["SSU processome","U3 snoRNP"],"partners":["NUP98","NOL10","AIM2","IMP4","RPL35","FBL","RAB27B","SQSTM1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13206","full_name":"Probable ATP-dependent RNA helicase DDX10","aliases":["DEAD box protein 10"],"length_aa":875,"mass_kda":100.9,"function":"Putative ATP-dependent RNA helicase that plays various role in innate immunity or inflammation. Plays a role in the enhancement of AIM2-induced inflammasome activation by interacting with AIM2 and stabilizing its protein level (PubMed:32519665). Negatively regulates viral infection by promoting interferon beta production and interferon stimulated genes/ISGs expression (PubMed:36779599)","subcellular_location":"Cytoplasm; Nucleus; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q13206/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DDX10","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"BYSL","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"IPO5","stoichiometry":0.2},{"gene":"LTV1","stoichiometry":0.2},{"gene":"TSR1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DDX10","total_profiled":1310},"omim":[{"mim_id":"601235","title":"DEAD-BOX HELICASE 10; DDX10","url":"https://www.omim.org/entry/601235"},{"mim_id":"601021","title":"NUCLEOPORIN, 98-KD; NUP98","url":"https://www.omim.org/entry/601021"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DDX10"},"hgnc":{"alias_symbol":["HRH-J8","Dbp4"],"prev_symbol":[]},"alphafold":{"accession":"Q13206","domains":[{"cath_id":"3.40.50.300","chopping":"48-276","consensus_level":"high","plddt":90.8746,"start":48,"end":276},{"cath_id":"3.40.50.300","chopping":"289-503","consensus_level":"high","plddt":90.5848,"start":289,"end":503}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13206","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13206-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13206-F1-predicted_aligned_error_v6.png","plddt_mean":70.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DDX10","jax_strain_url":"https://www.jax.org/strain/search?query=DDX10"},"sequence":{"accession":"Q13206","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13206.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13206/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13206"}},"corpus_meta":[{"pmid":"9166830","id":"PMC_9166830","title":"The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.","date":"1997","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/9166830","citation_count":137,"is_preprint":false},{"pmid":"19332556","id":"PMC_19332556","title":"A novel small-subunit processome assembly intermediate that contains the U3 snoRNP, nucleolin, RRP5, and DBP4.","date":"2009","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19332556","citation_count":59,"is_preprint":false},{"pmid":"36779599","id":"PMC_36779599","title":"Porcine reproductive and respiratory syndrome virus degrades DDX10 via SQSTM1/p62-dependent selective autophagy to antagonize its antiviral activity.","date":"2023","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/36779599","citation_count":53,"is_preprint":false},{"pmid":"20339440","id":"PMC_20339440","title":"Effects of the NUP98-DDX10 oncogene on primary human CD34+ cells: role of a conserved helicase motif.","date":"2010","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/20339440","citation_count":50,"is_preprint":false},{"pmid":"8660968","id":"PMC_8660968","title":"A human gene (DDX10) encoding a putative DEAD-box RNA helicase at 11q22-q23.","date":"1996","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8660968","citation_count":47,"is_preprint":false},{"pmid":"24450762","id":"PMC_24450762","title":"The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities.","date":"2014","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/24450762","citation_count":29,"is_preprint":false},{"pmid":"26713367","id":"PMC_26713367","title":"Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer.","date":"2015","source":"Biochemical and biophysical research 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IMP4.","date":"2021","source":"Thoracic cancer","url":"https://pubmed.ncbi.nlm.nih.gov/33973712","citation_count":17,"is_preprint":false},{"pmid":"35734237","id":"PMC_35734237","title":"UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury.","date":"2022","source":"Journal of diabetes research","url":"https://pubmed.ncbi.nlm.nih.gov/35734237","citation_count":14,"is_preprint":false},{"pmid":"30348128","id":"PMC_30348128","title":"Recombinant PAPP-A resistant insulin-like growth factor binding protein 4 (dBP4) inhibits angiogenesis and metastasis in a murine model of breast cancer.","date":"2018","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30348128","citation_count":14,"is_preprint":false},{"pmid":"17116492","id":"PMC_17116492","title":"Inversion (11)(p15q22) with NUP98-DDX10 fusion gene in pediatric acute myeloid leukemia.","date":"2006","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/17116492","citation_count":13,"is_preprint":false},{"pmid":"34797290","id":"PMC_34797290","title":"DDX10 and BYSL as the potential targets of chondrosarcoma and glioma.","date":"2021","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34797290","citation_count":9,"is_preprint":false},{"pmid":"39110225","id":"PMC_39110225","title":"ATG10-dependent autophagy is required for DDX10 to regulate cell proliferation, apoptosis and stemness in colorectal cancer.","date":"2024","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39110225","citation_count":4,"is_preprint":false},{"pmid":"40263434","id":"PMC_40263434","title":"Loss of NOL10 leads to impaired disease progression of NUP98::DDX10 leukemia.","date":"2025","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/40263434","citation_count":3,"is_preprint":false},{"pmid":"40352946","id":"PMC_40352946","title":"DDX10 Exacerbates Exosomal PD-L1-Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma.","date":"2025","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/40352946","citation_count":2,"is_preprint":false},{"pmid":"41338403","id":"PMC_41338403","title":"Reveal the regulatory role of DDX10 in diffuse large B-cell lymphoma: binding with FBL to promote cell proliferation and invasion.","date":"2025","source":"Molecular and cellular probes","url":"https://pubmed.ncbi.nlm.nih.gov/41338403","citation_count":1,"is_preprint":false},{"pmid":"41751522","id":"PMC_41751522","title":"DDX10 RNA Helicase: Structure, Function, and Oncogenic Roles Across Solid and Hematologic Tumors.","date":"2026","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/41751522","citation_count":0,"is_preprint":false},{"pmid":"36351646","id":"PMC_36351646","title":"[Acute myeloid leukemia harboring NUP98::DDX10].","date":"2022","source":"[Rinsho ketsueki] The Japanese journal of clinical hematology","url":"https://pubmed.ncbi.nlm.nih.gov/36351646","citation_count":0,"is_preprint":false},{"pmid":"32519665","id":"PMC_32519665","title":"[DDX10 promotes AIM2-inflammasome activation by maintaining AIM2 protein stability].","date":"2020","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/32519665","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15215,"output_tokens":3834,"usd":0.051577,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11576,"output_tokens":3773,"usd":0.076103,"stage2_stop_reason":"end_turn"},"total_usd":0.12768,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"DDX10 encodes a putative DEAD-box RNA helicase with predicted involvement in ribosome biogenesis, based on high sequence similarity to DEAD-box RNA helicases involved in ribosome biogenesis.\",\n      \"method\": \"Positional cloning, sequence analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence prediction only, no direct functional assay\",\n      \"pmids\": [\"8660968\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Inversion 11(p15q22) fuses NUP98 (nucleoporin) in-frame with DDX10 (putative RNA helicase) to produce the NUP98-DDX10 chimeric transcript; only the NUP98-DDX10 direction (not DDX10-NUP98) appears implicated in tumorigenesis.\",\n      \"method\": \"Positional cloning, RT-PCR, molecular characterization of translocation breakpoints in four patients\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal fusion characterized by molecular cloning, replicated across four patients and multiple subsequent studies\",\n      \"pmids\": [\"9166830\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Human DDX10 (ortholog of yeast Dbp4) is a component of a novel 50S U3 snoRNP assembly intermediate of the SSU processome; this complex accumulated when pre-rRNA transcription was blocked or tUTP proteins were depleted, and DDX10 was associated with the RNA-binding proteins nucleolin and RRP5 in this intermediate.\",\n      \"method\": \"Sucrose gradient sedimentation, co-immunoprecipitation, depletion experiments\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and depletion experiments in single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"19332556\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The conserved helicase motif YIHRAGRTAR in DDX10 (required for ATP binding, RNA binding, and helicase function) is required for the in vitro transforming ability of NUP98-DDX10; mutation of this motif diminishes leukemogenic transformation of CD34+ cells.\",\n      \"method\": \"Site-directed mutagenesis of helicase motif, transformation assay of primary human CD34+ cells, nuclear localization assay\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — active-site mutagenesis with functional transformation readout, single lab\",\n      \"pmids\": [\"20339440\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Yeast Dbp4 (DDX10 ortholog) interacts with nucleolar proteins Bfr2 and Enp2 in two distinct complexes: a 50S complex (not containing U3 snoRNA but containing U14 snoRNA associated with Dbp4) and an 80S SSU processome (containing U3 snoRNA); Bfr2 and Enp2 are required for early 18S rRNA processing steps.\",\n      \"method\": \"Sucrose gradient sedimentation, co-immunoprecipitation, northern blotting, genetic depletion\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (co-IP, sedimentation, northern blot), single lab\",\n      \"pmids\": [\"24357410\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Yeast Dbp4 (DDX10 ortholog) is required for SSU processome formation and cotranscriptional pre-rRNA cleavage: depletion of Dbp4 impairs early pre-rRNA cleavage, causes U14 snoRNA to remain associated with pre-rRNA, compromises SSU processome formation visible by electron microscopy, and its C-terminal extension (outside the catalytic core) is required for U14 snoRNA release from pre-rRNA. Dbp4 associates with U3 snoRNA and the U3-specific protein Mpp10 in whole-cell extracts but does not associate with U14 snoRNA.\",\n      \"method\": \"Immunoprecipitation, electron microscopy, sucrose density gradient analysis, genetic depletion, domain truncation analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods including EM, co-IP, sedimentation, and domain truncation in one study; findings consistent with prior work in same field\",\n      \"pmids\": [\"25535329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DDX10 (and yeast ortholog Dbp4) physically interacts with α-synuclein; α-synuclein sequesters DDX10 outside the nucleolus in both yeast and human cells, and this interaction stabilizes a fraction of α-synuclein oligomeric species. Downregulation of DBP4/DDX10 rescues cells from α-synuclein toxicity, while overexpression produces a synthetic lethal phenotype.\",\n      \"method\": \"Yeast genetic screen, co-immunoprecipitation, fluorescence microscopy (localization), genetic overexpression/knockdown with growth/toxicity readouts\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, live imaging, and genetic epistasis in single lab with orthogonal methods\",\n      \"pmids\": [\"33657088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DDX10 knockdown in lung cancer cells inhibits proliferation in vitro and in vivo; DDX10 positively correlates with the U3 snoRNP component IMP4, and IMP4 overexpression rescues the anti-proliferative effect of DDX10 knockdown, placing IMP4 downstream of DDX10.\",\n      \"method\": \"shRNA knockdown, in vitro proliferation assay, xenograft (in vivo), rescue experiment with IMP4 overexpression\",\n      \"journal\": \"Thoracic cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via rescue experiment, in vitro and in vivo, single lab\",\n      \"pmids\": [\"33973712\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DDX10 promotes AIM2 inflammasome activation by interacting with the HIN-200 domain of AIM2 and stabilizing AIM2 protein expression; DDX10 knockout in THP-1 macrophages inhibits AIM2 inflammasome activation (reduced caspase-1 cleavage and IL-1β release), and DDX10 co-localizes with AIM2 in HEK293T cells.\",\n      \"method\": \"Co-immunoprecipitation, ELISA (IL-1β), Western blot (caspase-1 cleavage), CRISPR knockout, immunofluorescence/confocal microscopy\",\n      \"journal\": \"Xi bao yu fen zi mian yi xue za zhi\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP identifying domain of interaction, KO with functional readout, co-localization, single lab\",\n      \"pmids\": [\"32519665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX10 interacts with RPL35 (identified by LC-MS/MS and confirmed by co-immunoprecipitation) and is linked to RNA splicing and E2F targets in colorectal cancer cells; DDX10 knockdown reduces CRC cell proliferation, migration, and invasion.\",\n      \"method\": \"LC-MS/MS proteomics, co-immunoprecipitation, shRNA knockdown, cell proliferation/migration/invasion assays, in vivo xenograft\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — binding partner identified by MS and confirmed by co-IP, functional KD phenotype, single lab\",\n      \"pmids\": [\"35109823\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PRRSV infection promotes DDX10 translocation from the nucleus to the cytoplasm for autophagic degradation. The viral envelope (E) protein interacts with DDX10, induces autophagy, and reduces DDX10 protein levels in wild-type cells but not in ATG5 or ATG7 KO cells. SQSTM1/p62 cargo receptor interacts with both DDX10 and E protein and mediates selective autophagic degradation of DDX10. DDX10 positively regulates type I interferon production, contributing to its antiviral effect against PRRSV.\",\n      \"method\": \"Co-immunoprecipitation, CRISPR knockout (ATG5, ATG7, SQSTM1), fluorescence microscopy (nuclear-cytoplasmic translocation), ectopic expression, siRNA knockdown, interferon reporter assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple KO cell lines, co-IP, mechanistic pathway dissection with multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"36779599\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DDX10 deletion in colorectal cancer cells increases ATG10 expression and activates autophagy; inhibition of ATG10 or treatment with the autophagy inhibitor 3-MA partially rescues the anti-proliferative and pro-apoptotic effects of DDX10 silencing, placing ATG10-dependent autophagy downstream of DDX10 in CRC cell regulation.\",\n      \"method\": \"siRNA knockdown, autophagy inhibitor (3-MA), Western blot, EDU staining (proliferation), TUNEL (apoptosis), sphere formation assay\",\n      \"journal\": \"Journal of cancer research and clinical oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via rescue with ATG10 depletion/inhibitor, multiple readouts, single lab\",\n      \"pmids\": [\"39110225\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Twenty-four amino acids within the DDX10 moiety of NUP98::DDX10 are required for cell immortalization and leukemogenesis; NOL10 (nucleolar protein 10) interacts with these 24 amino acids and is a critical dependency of NUP98::DDX10 leukemia. NOL10 acts cooperatively with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA; loss of Nol10 in a mouse model impairs NUP98::DDX10 leukemia progression.\",\n      \"method\": \"Domain mapping/mutagenesis, co-immunoprecipitation, mouse leukemia model with Nol10 knockout, mRNA stability assay, metabolic pathway analysis\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — domain mutagenesis, binding partner identification, in vivo mouse model, and metabolic pathway analysis in one study\",\n      \"pmids\": [\"40263434\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX10 physically interacts with Rab27b via phase separation and promotes Rab27b-mediated exosome secretion and PD-L1 loading into exosomes in oral squamous cell carcinoma; DDX10 knockdown inhibits exosomal PD-L1 secretion and restores T cell function and infiltration.\",\n      \"method\": \"Co-immunoprecipitation (phase separation assay), siRNA knockdown, exosome isolation, flow cytometry/immunofluorescence, T cell functional assays\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP demonstrating phase separation interaction, functional KD with multiple readouts, single lab\",\n      \"pmids\": [\"40352946\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX10 binds to fibrillarin (FBL) in DLBCL cells (confirmed by RNA immunoprecipitation); DDX10 and FBL positively regulate each other, and silencing either suppresses DLBCL cell viability, proliferation, invasion, and downregulates β-catenin, cyclin D1, and c-Myc (Wnt/β-catenin pathway components).\",\n      \"method\": \"RNA immunoprecipitation, siRNA knockdown, cell viability/invasion assays, Western blot (Wnt pathway proteins)\",\n      \"journal\": \"Molecular and cellular probes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP confirms interaction, functional KD with pathway readout, single lab\",\n      \"pmids\": [\"41338403\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX10 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis by promoting SSU processome formation, facilitating early pre-rRNA cleavage, and mediating release of U14 snoRNA from pre-rRNA via its C-terminal extension; it participates in antiviral innate immunity by positively regulating type I interferon production (and is degraded via SQSTM1-mediated selective autophagy during PRRSV infection); it interacts with AIM2 to stabilize it and promote inflammasome activation; it physically associates with α-synuclein (sequestering DDX10 from the nucleolus and stabilizing α-synuclein oligomers); and in the oncogenic NUP98::DDX10 fusion, a conserved helicase motif and interaction with NOL10 (which co-regulates serine biosynthesis and ATF4 mRNA stability) are required for leukemogenic transformation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DDX10 is a nucleolar DEAD-box RNA helicase that functions in small-subunit (SSU) ribosome biogenesis, where it (and its yeast ortholog Dbp4) is a component of U3 snoRNP/SSU processome assembly intermediates and associates with nucleolin, RRP5, and the U3-specific protein Mpp10 [#2, #5]. DDX10 is required for SSU processome formation and cotranscriptional pre-rRNA cleavage; its depletion impairs early pre-rRNA processing and traps U14 snoRNA on pre-rRNA, and its C-terminal extension outside the catalytic core mediates U14 snoRNA release [#5]. Beyond ribosome assembly, DDX10 positively regulates type I interferon production and acts as an antiviral factor, and during PRRSV infection it is translocated to the cytoplasm and degraded through SQSTM1/p62-mediated selective autophagy driven by the viral E protein [#10]; it also promotes AIM2 inflammasome activation by binding the HIN-200 domain of AIM2 and stabilizing AIM2 protein [#8]. DDX10 supports proliferation across several cancers and physically engages partners including IMP4, RPL35, fibrillarin, and Rab27b in these contexts [#7, #9, #14, #13]. The t(11;p15q22) inversion fuses NUP98 in-frame with DDX10, and the conserved YIHRAGRTAR helicase motif together with a 24-amino-acid segment that recruits NOL10 — a cooperating regulator of serine biosynthesis and ATF4 mRNA stability — is required for leukemogenic transformation [#1, #3, #12]. DDX10 additionally interacts with \\u03b1-synuclein, which sequesters it from the nucleolus and stabilizes \\u03b1-synuclein oligomers [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established DDX10 as a candidate DEAD-box RNA helicase, framing a hypothesis that it acts in ribosome biogenesis before any functional assay existed.\",\n      \"evidence\": \"positional cloning and sequence analysis\",\n      \"pmids\": [\"8660968\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"sequence prediction only, no functional assay\", \"no localization or substrate data\", \"helicase activity not demonstrated\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Showed DDX10 is recurrently fused to NUP98 by chromosomal inversion, defining its first disease association and pointing to an oncogenic gain-of-function specifically in the NUP98-DDX10 orientation.\",\n      \"evidence\": \"RT-PCR and breakpoint cloning across four leukemia patients\",\n      \"pmids\": [\"9166830\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"mechanism of transformation not defined\", \"did not test which DDX10 domains are required\", \"no normal cellular function established\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed human DDX10 in a defined 50S U3 snoRNP SSU-processome assembly intermediate, providing the first physical evidence for its predicted ribosome biogenesis role.\",\n      \"evidence\": \"sucrose gradient sedimentation, co-IP, and depletion in human cells\",\n      \"pmids\": [\"19332556\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"catalytic activity not demonstrated\", \"no rRNA processing readout in human cells\", \"function of nucleolin/RRP5 association unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrated that the conserved helicase motif of DDX10 is required for NUP98-DDX10 transformation, linking the enzyme's ATP/RNA-binding function to leukemogenesis.\",\n      \"evidence\": \"site-directed mutagenesis and CD34+ cell transformation assays\",\n      \"pmids\": [\"20339440\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"RNA substrate of the fusion not identified\", \"downstream target genes undefined\", \"single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the mechanistic step DDX10/Dbp4 catalyzes: SSU processome formation and cotranscriptional pre-rRNA cleavage, with the C-terminal extension required for U14 snoRNA release.\",\n      \"evidence\": \"immunoprecipitation, electron microscopy, sedimentation, and domain truncation in yeast\",\n      \"pmids\": [\"25535329\", \"24357410\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"human enzyme not directly assayed for U14 release\", \"ATP-dependent unwinding not reconstituted in vitro\", \"structural basis unknown\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended DDX10 function beyond the nucleolus into innate immunity by showing it stabilizes AIM2 and is required for inflammasome activation.\",\n      \"evidence\": \"co-IP domain mapping, CRISPR knockout in THP-1, and IL-1\\u03b2/caspase-1 readouts\",\n      \"pmids\": [\"32519665\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mechanism of AIM2 stabilization unknown\", \"whether helicase activity is required not tested\", \"single lab\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Connected DDX10 to disease beyond cancer and to proliferation control, showing it sequesters/stabilizes \\u03b1-synuclein oligomers and that IMP4 acts downstream in lung cancer growth.\",\n      \"evidence\": \"yeast genetic screen, co-IP, microscopy, and IMP4 rescue in lung cancer cells\",\n      \"pmids\": [\"33657088\", \"33973712\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"physiological relevance of \\u03b1-synuclein interaction in neurons untested\", \"how IMP4 mediates the growth effect unresolved\", \"single labs\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a regulated degradation pathway for DDX10 and assigned it a positive role in type I interferon production, establishing it as an antiviral host factor targeted by virus.\",\n      \"evidence\": \"co-IP, ATG5/ATG7/SQSTM1 knockouts, translocation imaging, and IFN reporter assays during PRRSV infection\",\n      \"pmids\": [\"36779599\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"molecular step by which DDX10 promotes IFN unknown\", \"whether RNA helicase activity is required for IFN role untested\", \"human relevance beyond PRRSV model unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified additional cancer-context partners and downstream programs, linking DDX10 to RPL35 and to autophagy regulation in colorectal cancer.\",\n      \"evidence\": \"LC-MS/MS, co-IP, siRNA knockdown with proliferation/apoptosis readouts and ATG10 epistasis\",\n      \"pmids\": [\"35109823\", \"39110225\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"whether DDX10 directly regulates ATG10 unknown\", \"mechanism linking RPL35 binding to phenotype unclear\", \"single labs\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Resolved the cooperating dependency of the NUP98::DDX10 fusion, showing a 24-residue DDX10 segment recruits NOL10 to drive serine biosynthesis and ATF4 mRNA stability required for leukemia.\",\n      \"evidence\": \"domain mutagenesis, co-IP, Nol10-knockout mouse leukemia model, and metabolic/mRNA stability assays\",\n      \"pmids\": [\"40263434\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"how NOL10 reprograms serine metabolism mechanistically unresolved\", \"whether NOL10 dependency applies to other NUP98 fusions untested\", \"role of normal DDX10-NOL10 interaction unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Broadened DDX10's cytoplasmic and tumor-immune roles, implicating it in Rab27b-mediated exosomal PD-L1 secretion and in fibrillarin-coupled Wnt/\\u03b2-catenin signaling.\",\n      \"evidence\": \"co-IP/phase separation assay, RNA immunoprecipitation, knockdown with exosome, T cell, and Wnt-pathway readouts\",\n      \"pmids\": [\"40352946\", \"41338403\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"how a nucleolar helicase engages cytoplasmic exosome machinery unresolved\", \"directness of Wnt pathway regulation unclear\", \"single labs\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether DDX10's diverse functions across ribosome biogenesis, innate immunity, autophagy, and cancer share a common biochemical activity, and whether its ATP-dependent RNA unwinding is required outside the SSU processome.\",\n      \"evidence\": \"no single study reconciles the nucleolar and extranucleolar roles\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no in vitro reconstitution of human DDX10 helicase activity\", \"RNA substrates in immune and cancer contexts unidentified\", \"structural basis of partner selectivity unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [3, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [2, 5, 6]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [8, 10]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 3, 12]}\n    ],\n    \"complexes\": [\"SSU processome\", \"U3 snoRNP\"],\n    \"partners\": [\"NUP98\", \"NOL10\", \"AIM2\", \"IMP4\", \"RPL35\", \"FBL\", \"Rab27b\", \"SQSTM1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}