{"gene":"DDX10","run_date":"2026-04-28T17:46:02","timeline":{"discoveries":[{"year":1996,"finding":"DDX10 was identified as a human gene encoding a putative DEAD-box RNA helicase at chromosome 11q22-q23, with predicted amino acid sequence showing high similarity to RNA helicases involved in ribosome biogenesis.","method":"Positional cloning, sequence analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 — original cloning with sequence similarity to functionally characterized family members, single study","pmids":["8660968"],"is_preprint":false},{"year":1997,"finding":"inv(11)(p15q22) chromosomal translocation fuses NUP98 (FG-repeat nucleoporin) to DDX10 (putative RNA helicase), producing the NUP98-DDX10 chimeric transcript implicated in myeloid leukemogenesis; only the NUP98-DDX10 (not DDX10-NUP98) fusion appears oncogenic.","method":"Positional cloning, RT-PCR, molecular characterization of breakpoints","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 — replicated across multiple patients and labs, foundational highly-cited study","pmids":["9166830"],"is_preprint":false},{"year":2010,"finding":"NUP98-DDX10 fusion protein dramatically increases proliferation and self-renewal of primary human CD34+ cells and disrupts erythroid/myeloid differentiation; it localizes to the nucleus and extensively deregulates gene expression including HOX genes. Mutation of the conserved YIHRAGRTAR helicase motif (required for ATP binding, RNA binding, and helicase function) in the DDX10 portion diminished in vitro transforming ability, demonstrating the helicase domain contributes to leukemogenesis.","method":"Retroviral transduction of primary human CD34+ cells, site-directed mutagenesis of helicase motif, colony assays, gene expression profiling","journal":"Leukemia","confidence":"High","confidence_rationale":"Tier 1-2 — mutagenesis of catalytic motif combined with primary cell functional assays","pmids":["20339440"],"is_preprint":false},{"year":2009,"finding":"DBP4 (human ortholog DDX10) associates with the U3 snoRNP and is recruited to a novel 50S SSU processome assembly intermediate together with nucleolin and RRP5, suggesting DDX10 functions in small subunit ribosome biogenesis at an early assembly step.","method":"Immunoprecipitation, sucrose gradient sedimentation, siRNA depletion, native complex analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP and gradient sedimentation with depletion experiments, replicated in multiple studies","pmids":["19332556"],"is_preprint":false},{"year":2013,"finding":"Yeast Dbp4 (DDX10 ortholog) interacts with nucleolar proteins Bfr2 and Enp2 in two distinct complexes: a ~50S complex (containing U14 snoRNA but not U3 snoRNA) and an ~80S SSU processome (containing U3 snoRNA); all three proteins are required for early 18S rRNA processing steps.","method":"Immunoprecipitation, sucrose gradient sedimentation, snoRNA association assays, genetic depletion","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (IP, gradients, RNA association), mechanistically distinct complexes defined","pmids":["24357410"],"is_preprint":false},{"year":2014,"finding":"Yeast Dbp4 (DDX10 ortholog) is required for SSU processome formation and function: depletion impairs early pre-rRNA cleavage reactions and causes U14 snoRNA to remain abnormally associated with pre-rRNA; Dbp4 associates with U3 snoRNA and the U3-specific protein Mpp10 in the SSU processome; electron microscopy showed depletion compromised cotranscriptional SSU processome formation; the C-terminal extension of Dbp4 is required for release of U14 snoRNA from pre-rRNA.","method":"Immunoprecipitation, electron microscopy, sucrose density gradient, genetic depletion, domain truncation analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including EM structural analysis, domain mutagenesis, and functional assays in single study","pmids":["25535329"],"is_preprint":false},{"year":2021,"finding":"α-Synuclein physically interacts with Dbp4/DDX10 and sequesters it outside the nucleolus in both yeast and human cells; DDX10 overexpression worsens α-synuclein toxicity and promotes α-synuclein oligomerization, while downregulation rescues cells from toxicity, establishing DDX10 as a modulator of α-synuclein aggregation linked to its nucleolar function.","method":"Yeast genetic screen, co-immunoprecipitation, fluorescence microscopy (co-localization), α-synuclein oligomerization assay, genetic overexpression and knockdown","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 — direct protein interaction demonstrated with co-IP and localization, functional consequence shown in two model systems","pmids":["33657088"],"is_preprint":false},{"year":2021,"finding":"DDX10 promotes lung carcinoma cell proliferation through a functional link with IMP4 (U3 small nucleolar ribonucleoprotein component); DDX10 knockdown inhibited proliferation, and IMP4 overexpression reversed the effects of DDX10 knockdown on proliferation and apoptosis.","method":"shRNA knockdown, in vitro and in vivo proliferation assays, IMP4 rescue overexpression","journal":"Thoracic cancer","confidence":"Medium","confidence_rationale":"Tier 3 — genetic epistasis via rescue experiment, single lab study without direct biochemical interaction assay","pmids":["33973712"],"is_preprint":false},{"year":2022,"finding":"DDX10 promotes CRC cell proliferation, migration, and invasion; LC-MS/MS and Co-IP identified RPL35 as a DDX10-interacting protein, and DDX10 was linked to RNA splicing and E2F targets via gene set enrichment analysis.","method":"LC-MS/MS, co-immunoprecipitation, shRNA knockdown, in vitro/in vivo functional assays, GSEA","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 3 — Co-IP binding partner identified with mass spectrometry, but mechanistic link between RPL35 interaction and cancer phenotype not fully resolved","pmids":["35109823"],"is_preprint":false},{"year":2023,"finding":"PRRSV infection promotes DDX10 translocation from the nucleus to the cytoplasm, where it undergoes SQSTM1/p62-mediated selective autophagic degradation; the viral E protein interacts with DDX10 and induces this autophagy-dependent degradation (blocked in ATG5, ATG7, or SQSTM1 KO cells); DDX10 positively regulates type I interferon production and has antiviral activity against PRRSV.","method":"Co-immunoprecipitation, knockout cell lines (ATG5, ATG7, SQSTM1 KO), indirect immunofluorescence, siRNA knockdown, overexpression, ELISA for IFN-β","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 2 — multiple KO cell lines used as genetic validation, direct protein interaction confirmed by Co-IP, multiple orthogonal methods in single study","pmids":["36779599"],"is_preprint":false},{"year":2020,"finding":"DDX10 interacts with the HIN-200 domain of AIM2 and stabilizes AIM2 protein expression, thereby promoting AIM2 inflammasome activation; DDX10 deficiency in THP-1 macrophages inhibited AIM2-driven caspase-1 cleavage and IL-1β release.","method":"Co-immunoprecipitation, immunofluorescence, ELISA, Western blot, DDX10 knockout THP-1 cells, overexpression screen","journal":"Chinese journal of cellular and molecular immunology","confidence":"Medium","confidence_rationale":"Tier 3 — Co-IP interaction confirmed, KO functional phenotype shown, single study","pmids":["32519665"],"is_preprint":false},{"year":2025,"finding":"A 24-amino-acid region within the DDX10 moiety of NUP98::DDX10 is required for cell immortalization and leukemogenesis; NOL10 (nucleolar protein 10) interacts with these 24 amino acids and acts as a critical co-factor for NUP98::DDX10 leukemia; NOL10 cooperates with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA.","method":"Domain deletion/mutagenesis, Co-immunoprecipitation, mouse leukemia model (Nol10 knockout), RT-PCR/mRNA stability assays, metabolic pathway analysis","journal":"Leukemia","confidence":"High","confidence_rationale":"Tier 1-2 — domain mapping with mutagenesis combined with in vivo mouse model and direct binding partner identification, multiple orthogonal methods","pmids":["40263434"],"is_preprint":false},{"year":2025,"finding":"DDX10 undergoes liquid-liquid phase separation with Rab27b in oral squamous cell carcinoma cells; DDX10 knockdown inhibits Rab27b-mediated exosome secretion and reduces PD-L1 content in exosomes, thereby restoring T cell function and infiltration.","method":"Co-immunoprecipitation (physical interaction with Rab27b), phase separation assay, exosome quantification, PD-L1 measurement in exosomes, T cell functional assays, DDX10 knockdown","journal":"Research (Washington, D.C.)","confidence":"Medium","confidence_rationale":"Tier 3 — direct interaction and phase separation shown, functional consequence on exosome secretion established, single lab study","pmids":["40352946"],"is_preprint":false},{"year":2024,"finding":"DDX10 deficiency activates ATG10-dependent autophagy in colorectal cancer cells; ATG10 depletion or autophagy inhibition (3-MA) partially rescues the effects of DDX10 knockdown on proliferation, apoptosis, and stemness, placing DDX10 upstream of ATG10-mediated autophagy.","method":"siRNA/shRNA knockdown, EDU staining, TUNEL assay, sphere formation, Western blot, immunofluorescence, autophagy inhibitor treatment","journal":"Journal of cancer research and clinical oncology","confidence":"Medium","confidence_rationale":"Tier 3 — genetic epistasis via rescue experiment, pathway placement shown, single lab","pmids":["39110225"],"is_preprint":false},{"year":2025,"finding":"DDX10 binds to FBL (fibrillarin) in DLBCL cells as confirmed by RNA immunoprecipitation; silencing either DDX10 or FBL suppresses proliferation, invasion, and Wnt/β-catenin pathway (β-catenin, cyclin D1, c-Myc); overexpression of one partner rescues silencing of the other, indicating a cooperative DDX10-FBL axis.","method":"RNA immunoprecipitation, siRNA knockdown, overexpression rescue, Western blot for pathway markers, viability and invasion assays","journal":"Molecular and cellular probes","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP/RIP interaction with rescue epistasis, single lab, limited mechanistic resolution","pmids":["41338403"],"is_preprint":false},{"year":2015,"finding":"DDX10 is epigenetically silenced by miR-155-5p in ovarian cancer; loss of DDX10 promotes ovarian cancer cell proliferation in vitro and tumor formation in vivo via activation of the Akt/NF-κB pathway.","method":"miRNA overexpression/inhibition, gain- and loss-of-function assays, xenograft tumor model, pathway inhibitor analysis","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 — pathway placement via inhibitor experiments, miRNA regulation shown, single lab without direct biochemical mechanistic validation","pmids":["26713367"],"is_preprint":false}],"current_model":"DDX10 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis by participating in small subunit (SSU) processome assembly, facilitating U14 snoRNA release from pre-rRNA and early 18S rRNA processing steps; it positively regulates type I interferon production and AIM2 inflammasome activation (by stabilizing AIM2 protein), undergoes SQSTM1-mediated selective autophagic degradation upon viral infection, can interact with Rab27b via phase separation to regulate exosomal PD-L1 secretion, and when fused to NUP98 via inv(11)(p15q22), drives myeloid leukemogenesis in a manner partially dependent on its conserved helicase motif and its interaction with the co-factor NOL10."},"narrative":{"teleology":[{"year":1996,"claim":"Identification of DDX10 as a DEAD-box helicase gene at 11q22-q23 established the gene's membership in the RNA helicase family and predicted a role in ribosome biogenesis based on sequence homology.","evidence":"Positional cloning and sequence analysis of human DDX10","pmids":["8660968"],"confidence":"Medium","gaps":["No direct functional data; role inferred solely from sequence similarity","Subcellular localization not experimentally determined"]},{"year":1997,"claim":"Discovery of the NUP98-DDX10 fusion from inv(11)(p15q22) in myeloid leukemia established DDX10 as a partner in a recurrent oncogenic translocation, raising the question of which domains contribute to transformation.","evidence":"Positional cloning and RT-PCR characterization of translocation breakpoints in leukemia patients","pmids":["9166830"],"confidence":"High","gaps":["Transforming activity not yet tested functionally","Contribution of DDX10 helicase activity versus NUP98 FG-repeats unresolved"]},{"year":2009,"claim":"Demonstration that DDX10 (Dbp4) associates with the U3 snoRNP within a novel 50S SSU processome intermediate established it as a bona fide ribosome biogenesis factor rather than merely a predicted helicase.","evidence":"Immunoprecipitation, sucrose gradient sedimentation, and siRNA depletion in human/yeast cells","pmids":["19332556"],"confidence":"High","gaps":["Enzymatic activity on pre-rRNA not directly measured","Human-specific complex composition not fully defined"]},{"year":2010,"claim":"Mutagenesis of the conserved helicase motif in NUP98-DDX10 showed that the DDX10 helicase domain actively contributes to leukemic transformation, resolving whether DDX10 is a passive fusion partner.","evidence":"Site-directed mutagenesis of YIHRAGRTAR motif, retroviral transduction of primary human CD34+ cells, colony assays","pmids":["20339440"],"confidence":"High","gaps":["Specific RNA substrates of the helicase in the oncogenic context unknown","HOX gene deregulation mechanism not fully resolved"]},{"year":2013,"claim":"Resolution of two distinct Dbp4/DDX10-containing complexes—a ~50S complex with U14 snoRNA and an ~80S SSU processome with U3 snoRNA—clarified that DDX10 operates at multiple steps of pre-ribosomal assembly.","evidence":"Immunoprecipitation, sucrose gradient sedimentation, and snoRNA association assays in yeast","pmids":["24357410"],"confidence":"High","gaps":["Order of DDX10 recruitment to the two complexes not established","Whether the two complexes represent sequential maturation intermediates unclear"]},{"year":2014,"claim":"Defining that DDX10's C-terminal extension is required for U14 snoRNA release from pre-rRNA, and that DDX10 depletion blocks cotranscriptional SSU processome formation, established the precise mechanistic step catalyzed by this helicase in ribosome biogenesis.","evidence":"Domain truncation analysis, electron microscopy of rDNA chromatin spreads, genetic depletion in yeast","pmids":["25535329"],"confidence":"High","gaps":["Direct unwinding of U14-pre-rRNA duplex not reconstituted in vitro","No structural model of DDX10 in the SSU processome context"]},{"year":2020,"claim":"Identification of DDX10 as a stabilizer of AIM2 protein and promoter of AIM2 inflammasome activation revealed a role outside ribosome biogenesis, in innate immune sensing of cytosolic DNA.","evidence":"Co-IP with AIM2 HIN-200 domain, DDX10 knockout THP-1 macrophages, caspase-1 cleavage and IL-1β ELISA","pmids":["32519665"],"confidence":"Medium","gaps":["Mechanism of AIM2 protein stabilization (e.g., prevention of degradation) not defined","Not independently replicated","Whether helicase activity is required for AIM2 stabilization unknown"]},{"year":2021,"claim":"Discovery that α-synuclein sequesters DDX10 outside the nucleolus and that DDX10 modulates α-synuclein oligomerization linked its nucleolar function to neurodegeneration-relevant proteotoxicity.","evidence":"Yeast genetic screen, co-IP, fluorescence microscopy in yeast and human cells, α-synuclein oligomerization assay","pmids":["33657088"],"confidence":"Medium","gaps":["Whether DDX10 directly chaperones α-synuclein aggregation or acts indirectly unknown","Relevance to Parkinson's disease pathology in vivo not tested"]},{"year":2023,"claim":"Showing that viral infection triggers SQSTM1/p62-mediated selective autophagic degradation of DDX10 in the cytoplasm, and that DDX10 positively regulates type I interferon production, established DDX10 as an antiviral innate immune effector targeted by pathogen evasion strategies.","evidence":"Co-IP with viral E protein, ATG5/ATG7/SQSTM1 knockout cell lines, IFN-β ELISA, immunofluorescence of DDX10 translocation","pmids":["36779599"],"confidence":"High","gaps":["Molecular mechanism by which DDX10 promotes IFN signaling not defined (RNA target, signaling intermediate)","Whether this antiviral role generalizes beyond PRRSV not established"]},{"year":2025,"claim":"Mapping a 24-amino-acid region in DDX10 that recruits NOL10 as a critical cofactor for NUP98::DDX10-driven leukemia, with downstream regulation of serine biosynthesis and ATF4 mRNA stability, provided the most detailed mechanistic dissection of the fusion oncoprotein to date.","evidence":"Domain deletion/mutagenesis, Co-IP with NOL10, Nol10 knockout mouse leukemia model, mRNA stability assays","pmids":["40263434"],"confidence":"High","gaps":["Whether NOL10 interaction reflects a normal DDX10 function or is neomorphic in the fusion context unclear","Structural basis of the 24-amino-acid–NOL10 interaction not resolved"]},{"year":2025,"claim":"DDX10 was shown to undergo liquid-liquid phase separation with Rab27b, regulating exosomal PD-L1 secretion and thereby modulating anti-tumor immune responses, extending DDX10 function to exosome biology and immune evasion.","evidence":"Phase separation assay, Co-IP, exosome quantification, PD-L1 measurement, T cell functional assays in oral squamous cell carcinoma cells","pmids":["40352946"],"confidence":"Medium","gaps":["Phase separation properties of DDX10 alone not characterized biophysically","Whether RNA helicase activity is required for the Rab27b interaction and phase separation unknown","Single lab study"]},{"year":null,"claim":"Key unresolved questions include the direct RNA substrates of human DDX10 in ribosome biogenesis and immune signaling, the structural basis of DDX10 within the SSU processome, and the mechanism by which DDX10 promotes type I interferon production.","evidence":"","pmids":[],"confidence":"High","gaps":["No in vitro reconstitution of DDX10 helicase activity on physiological RNA substrates","No high-resolution structure of DDX10 in any complex","Mechanism linking DDX10 to IFN-β transcription or signaling pathway unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,3,4,5]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,2,5]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[9,10]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[3,4,5,6]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,4,5]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[3,4,5]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[9,10]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,2,11]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[9,13]}],"complexes":["SSU processome (90S pre-ribosome)","U14 snoRNP-containing 50S complex"],"partners":["NUP98","NOL10","AIM2","SQSTM1","FBL","RAB27B","RPL35","IMP4"],"other_free_text":[]},"mechanistic_narrative":"DDX10 is a nucleolar DEAD-box RNA helicase that functions centrally in small ribosomal subunit (SSU) biogenesis, with additional roles in innate immune signaling and oncogenic transformation when fused to NUP98. Within the nucleolus, DDX10 (yeast ortholog Dbp4) associates with U3 and U14 snoRNPs in distinct pre-ribosomal complexes, facilitates cotranscriptional SSU processome assembly, and is required for U14 snoRNA release from pre-rRNA and early 18S rRNA cleavage steps, with its C-terminal extension essential for U14 release [PMID:19332556, PMID:24357410, PMID:25535329]. DDX10 positively regulates type I interferon production and is targeted for SQSTM1/p62-mediated selective autophagic degradation during viral infection, and it stabilizes the AIM2 inflammasome sensor to promote caspase-1 activation and IL-1β release [PMID:36779599, PMID:32519665]. The inv(11)(p15q22) translocation generates a NUP98-DDX10 fusion oncoprotein that drives myeloid leukemogenesis through its helicase motif and a 24-amino-acid region that recruits the cofactor NOL10 to regulate serine biosynthesis and ATF4 mRNA stability [PMID:9166830, PMID:20339440, PMID:40263434]."},"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":135,"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":"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":"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":49,"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":"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":"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":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":"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},{"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14452,"output_tokens":3857,"usd":0.050605},"stage2":{"model":"claude-opus-4-6","input_tokens":7310,"output_tokens":3070,"usd":0.16995},"total_usd":0.220555,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"DDX10 was identified as a human gene encoding a putative DEAD-box RNA helicase at chromosome 11q22-q23, with predicted amino acid sequence showing high similarity to RNA helicases involved in ribosome biogenesis.\",\n      \"method\": \"Positional cloning, sequence analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — original cloning with sequence similarity to functionally characterized family members, single study\",\n      \"pmids\": [\"8660968\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"inv(11)(p15q22) chromosomal translocation fuses NUP98 (FG-repeat nucleoporin) to DDX10 (putative RNA helicase), producing the NUP98-DDX10 chimeric transcript implicated in myeloid leukemogenesis; only the NUP98-DDX10 (not DDX10-NUP98) fusion appears oncogenic.\",\n      \"method\": \"Positional cloning, RT-PCR, molecular characterization of breakpoints\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — replicated across multiple patients and labs, foundational highly-cited study\",\n      \"pmids\": [\"9166830\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"NUP98-DDX10 fusion protein dramatically increases proliferation and self-renewal of primary human CD34+ cells and disrupts erythroid/myeloid differentiation; it localizes to the nucleus and extensively deregulates gene expression including HOX genes. Mutation of the conserved YIHRAGRTAR helicase motif (required for ATP binding, RNA binding, and helicase function) in the DDX10 portion diminished in vitro transforming ability, demonstrating the helicase domain contributes to leukemogenesis.\",\n      \"method\": \"Retroviral transduction of primary human CD34+ cells, site-directed mutagenesis of helicase motif, colony assays, gene expression profiling\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — mutagenesis of catalytic motif combined with primary cell functional assays\",\n      \"pmids\": [\"20339440\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"DBP4 (human ortholog DDX10) associates with the U3 snoRNP and is recruited to a novel 50S SSU processome assembly intermediate together with nucleolin and RRP5, suggesting DDX10 functions in small subunit ribosome biogenesis at an early assembly step.\",\n      \"method\": \"Immunoprecipitation, sucrose gradient sedimentation, siRNA depletion, native complex analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and gradient sedimentation with depletion experiments, replicated in multiple studies\",\n      \"pmids\": [\"19332556\"],\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 (containing U14 snoRNA but not U3 snoRNA) and an ~80S SSU processome (containing U3 snoRNA); all three proteins are required for early 18S rRNA processing steps.\",\n      \"method\": \"Immunoprecipitation, sucrose gradient sedimentation, snoRNA association assays, genetic depletion\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (IP, gradients, RNA association), mechanistically distinct complexes defined\",\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 function: depletion impairs early pre-rRNA cleavage reactions and causes U14 snoRNA to remain abnormally associated with pre-rRNA; Dbp4 associates with U3 snoRNA and the U3-specific protein Mpp10 in the SSU processome; electron microscopy showed depletion compromised cotranscriptional SSU processome formation; the C-terminal extension of Dbp4 is required for release of U14 snoRNA from pre-rRNA.\",\n      \"method\": \"Immunoprecipitation, electron microscopy, sucrose density gradient, genetic depletion, domain truncation analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including EM structural analysis, domain mutagenesis, and functional assays in single study\",\n      \"pmids\": [\"25535329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"α-Synuclein physically interacts with Dbp4/DDX10 and sequesters it outside the nucleolus in both yeast and human cells; DDX10 overexpression worsens α-synuclein toxicity and promotes α-synuclein oligomerization, while downregulation rescues cells from toxicity, establishing DDX10 as a modulator of α-synuclein aggregation linked to its nucleolar function.\",\n      \"method\": \"Yeast genetic screen, co-immunoprecipitation, fluorescence microscopy (co-localization), α-synuclein oligomerization assay, genetic overexpression and knockdown\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct protein interaction demonstrated with co-IP and localization, functional consequence shown in two model systems\",\n      \"pmids\": [\"33657088\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"DDX10 promotes lung carcinoma cell proliferation through a functional link with IMP4 (U3 small nucleolar ribonucleoprotein component); DDX10 knockdown inhibited proliferation, and IMP4 overexpression reversed the effects of DDX10 knockdown on proliferation and apoptosis.\",\n      \"method\": \"shRNA knockdown, in vitro and in vivo proliferation assays, IMP4 rescue overexpression\",\n      \"journal\": \"Thoracic cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic epistasis via rescue experiment, single lab study without direct biochemical interaction assay\",\n      \"pmids\": [\"33973712\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX10 promotes CRC cell proliferation, migration, and invasion; LC-MS/MS and Co-IP identified RPL35 as a DDX10-interacting protein, and DDX10 was linked to RNA splicing and E2F targets via gene set enrichment analysis.\",\n      \"method\": \"LC-MS/MS, co-immunoprecipitation, shRNA knockdown, in vitro/in vivo functional assays, GSEA\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP binding partner identified with mass spectrometry, but mechanistic link between RPL35 interaction and cancer phenotype not fully resolved\",\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, where it undergoes SQSTM1/p62-mediated selective autophagic degradation; the viral E protein interacts with DDX10 and induces this autophagy-dependent degradation (blocked in ATG5, ATG7, or SQSTM1 KO cells); DDX10 positively regulates type I interferon production and has antiviral activity against PRRSV.\",\n      \"method\": \"Co-immunoprecipitation, knockout cell lines (ATG5, ATG7, SQSTM1 KO), indirect immunofluorescence, siRNA knockdown, overexpression, ELISA for IFN-β\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple KO cell lines used as genetic validation, direct protein interaction confirmed by Co-IP, multiple orthogonal methods in single study\",\n      \"pmids\": [\"36779599\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DDX10 interacts with the HIN-200 domain of AIM2 and stabilizes AIM2 protein expression, thereby promoting AIM2 inflammasome activation; DDX10 deficiency in THP-1 macrophages inhibited AIM2-driven caspase-1 cleavage and IL-1β release.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, ELISA, Western blot, DDX10 knockout THP-1 cells, overexpression screen\",\n      \"journal\": \"Chinese journal of cellular and molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — Co-IP interaction confirmed, KO functional phenotype shown, single study\",\n      \"pmids\": [\"32519665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A 24-amino-acid region within the DDX10 moiety of NUP98::DDX10 is required for cell immortalization and leukemogenesis; NOL10 (nucleolar protein 10) interacts with these 24 amino acids and acts as a critical co-factor for NUP98::DDX10 leukemia; NOL10 cooperates with NUP98::DDX10 to regulate serine biosynthesis pathways and stabilize ATF4 mRNA.\",\n      \"method\": \"Domain deletion/mutagenesis, Co-immunoprecipitation, mouse leukemia model (Nol10 knockout), RT-PCR/mRNA stability assays, metabolic pathway analysis\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — domain mapping with mutagenesis combined with in vivo mouse model and direct binding partner identification, multiple orthogonal methods\",\n      \"pmids\": [\"40263434\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX10 undergoes liquid-liquid phase separation with Rab27b in oral squamous cell carcinoma cells; DDX10 knockdown inhibits Rab27b-mediated exosome secretion and reduces PD-L1 content in exosomes, thereby restoring T cell function and infiltration.\",\n      \"method\": \"Co-immunoprecipitation (physical interaction with Rab27b), phase separation assay, exosome quantification, PD-L1 measurement in exosomes, T cell functional assays, DDX10 knockdown\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct interaction and phase separation shown, functional consequence on exosome secretion established, single lab study\",\n      \"pmids\": [\"40352946\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DDX10 deficiency activates ATG10-dependent autophagy in colorectal cancer cells; ATG10 depletion or autophagy inhibition (3-MA) partially rescues the effects of DDX10 knockdown on proliferation, apoptosis, and stemness, placing DDX10 upstream of ATG10-mediated autophagy.\",\n      \"method\": \"siRNA/shRNA knockdown, EDU staining, TUNEL assay, sphere formation, Western blot, immunofluorescence, autophagy inhibitor treatment\",\n      \"journal\": \"Journal of cancer research and clinical oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic epistasis via rescue experiment, pathway placement shown, single lab\",\n      \"pmids\": [\"39110225\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX10 binds to FBL (fibrillarin) in DLBCL cells as confirmed by RNA immunoprecipitation; silencing either DDX10 or FBL suppresses proliferation, invasion, and Wnt/β-catenin pathway (β-catenin, cyclin D1, c-Myc); overexpression of one partner rescues silencing of the other, indicating a cooperative DDX10-FBL axis.\",\n      \"method\": \"RNA immunoprecipitation, siRNA knockdown, overexpression rescue, Western blot for pathway markers, viability and invasion assays\",\n      \"journal\": \"Molecular and cellular probes\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP/RIP interaction with rescue epistasis, single lab, limited mechanistic resolution\",\n      \"pmids\": [\"41338403\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DDX10 is epigenetically silenced by miR-155-5p in ovarian cancer; loss of DDX10 promotes ovarian cancer cell proliferation in vitro and tumor formation in vivo via activation of the Akt/NF-κB pathway.\",\n      \"method\": \"miRNA overexpression/inhibition, gain- and loss-of-function assays, xenograft tumor model, pathway inhibitor analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — pathway placement via inhibitor experiments, miRNA regulation shown, single lab without direct biochemical mechanistic validation\",\n      \"pmids\": [\"26713367\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX10 is a nucleolar DEAD-box RNA helicase that functions in ribosome biogenesis by participating in small subunit (SSU) processome assembly, facilitating U14 snoRNA release from pre-rRNA and early 18S rRNA processing steps; it positively regulates type I interferon production and AIM2 inflammasome activation (by stabilizing AIM2 protein), undergoes SQSTM1-mediated selective autophagic degradation upon viral infection, can interact with Rab27b via phase separation to regulate exosomal PD-L1 secretion, and when fused to NUP98 via inv(11)(p15q22), drives myeloid leukemogenesis in a manner partially dependent on its conserved helicase motif and its interaction with the co-factor NOL10.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DDX10 is a nucleolar DEAD-box RNA helicase that functions centrally in small ribosomal subunit (SSU) biogenesis, with additional roles in innate immune signaling and oncogenic transformation when fused to NUP98. Within the nucleolus, DDX10 (yeast ortholog Dbp4) associates with U3 and U14 snoRNPs in distinct pre-ribosomal complexes, facilitates cotranscriptional SSU processome assembly, and is required for U14 snoRNA release from pre-rRNA and early 18S rRNA cleavage steps, with its C-terminal extension essential for U14 release [PMID:19332556, PMID:24357410, PMID:25535329]. DDX10 positively regulates type I interferon production and is targeted for SQSTM1/p62-mediated selective autophagic degradation during viral infection, and it stabilizes the AIM2 inflammasome sensor to promote caspase-1 activation and IL-1β release [PMID:36779599, PMID:32519665]. The inv(11)(p15q22) translocation generates a NUP98-DDX10 fusion oncoprotein that drives myeloid leukemogenesis through its helicase motif and a 24-amino-acid region that recruits the cofactor NOL10 to regulate serine biosynthesis and ATF4 mRNA stability [PMID:9166830, PMID:20339440, PMID:40263434].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Identification of DDX10 as a DEAD-box helicase gene at 11q22-q23 established the gene's membership in the RNA helicase family and predicted a role in ribosome biogenesis based on sequence homology.\",\n      \"evidence\": \"Positional cloning and sequence analysis of human DDX10\",\n      \"pmids\": [\"8660968\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct functional data; role inferred solely from sequence similarity\", \"Subcellular localization not experimentally determined\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Discovery of the NUP98-DDX10 fusion from inv(11)(p15q22) in myeloid leukemia established DDX10 as a partner in a recurrent oncogenic translocation, raising the question of which domains contribute to transformation.\",\n      \"evidence\": \"Positional cloning and RT-PCR characterization of translocation breakpoints in leukemia patients\",\n      \"pmids\": [\"9166830\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Transforming activity not yet tested functionally\", \"Contribution of DDX10 helicase activity versus NUP98 FG-repeats unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Demonstration that DDX10 (Dbp4) associates with the U3 snoRNP within a novel 50S SSU processome intermediate established it as a bona fide ribosome biogenesis factor rather than merely a predicted helicase.\",\n      \"evidence\": \"Immunoprecipitation, sucrose gradient sedimentation, and siRNA depletion in human/yeast cells\",\n      \"pmids\": [\"19332556\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Enzymatic activity on pre-rRNA not directly measured\", \"Human-specific complex composition not fully defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mutagenesis of the conserved helicase motif in NUP98-DDX10 showed that the DDX10 helicase domain actively contributes to leukemic transformation, resolving whether DDX10 is a passive fusion partner.\",\n      \"evidence\": \"Site-directed mutagenesis of YIHRAGRTAR motif, retroviral transduction of primary human CD34+ cells, colony assays\",\n      \"pmids\": [\"20339440\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific RNA substrates of the helicase in the oncogenic context unknown\", \"HOX gene deregulation mechanism not fully resolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Resolution of two distinct Dbp4/DDX10-containing complexes—a ~50S complex with U14 snoRNA and an ~80S SSU processome with U3 snoRNA—clarified that DDX10 operates at multiple steps of pre-ribosomal assembly.\",\n      \"evidence\": \"Immunoprecipitation, sucrose gradient sedimentation, and snoRNA association assays in yeast\",\n      \"pmids\": [\"24357410\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Order of DDX10 recruitment to the two complexes not established\", \"Whether the two complexes represent sequential maturation intermediates unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defining that DDX10's C-terminal extension is required for U14 snoRNA release from pre-rRNA, and that DDX10 depletion blocks cotranscriptional SSU processome formation, established the precise mechanistic step catalyzed by this helicase in ribosome biogenesis.\",\n      \"evidence\": \"Domain truncation analysis, electron microscopy of rDNA chromatin spreads, genetic depletion in yeast\",\n      \"pmids\": [\"25535329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct unwinding of U14-pre-rRNA duplex not reconstituted in vitro\", \"No structural model of DDX10 in the SSU processome context\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identification of DDX10 as a stabilizer of AIM2 protein and promoter of AIM2 inflammasome activation revealed a role outside ribosome biogenesis, in innate immune sensing of cytosolic DNA.\",\n      \"evidence\": \"Co-IP with AIM2 HIN-200 domain, DDX10 knockout THP-1 macrophages, caspase-1 cleavage and IL-1β ELISA\",\n      \"pmids\": [\"32519665\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of AIM2 protein stabilization (e.g., prevention of degradation) not defined\", \"Not independently replicated\", \"Whether helicase activity is required for AIM2 stabilization unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Discovery that α-synuclein sequesters DDX10 outside the nucleolus and that DDX10 modulates α-synuclein oligomerization linked its nucleolar function to neurodegeneration-relevant proteotoxicity.\",\n      \"evidence\": \"Yeast genetic screen, co-IP, fluorescence microscopy in yeast and human cells, α-synuclein oligomerization assay\",\n      \"pmids\": [\"33657088\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DDX10 directly chaperones α-synuclein aggregation or acts indirectly unknown\", \"Relevance to Parkinson's disease pathology in vivo not tested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showing that viral infection triggers SQSTM1/p62-mediated selective autophagic degradation of DDX10 in the cytoplasm, and that DDX10 positively regulates type I interferon production, established DDX10 as an antiviral innate immune effector targeted by pathogen evasion strategies.\",\n      \"evidence\": \"Co-IP with viral E protein, ATG5/ATG7/SQSTM1 knockout cell lines, IFN-β ELISA, immunofluorescence of DDX10 translocation\",\n      \"pmids\": [\"36779599\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which DDX10 promotes IFN signaling not defined (RNA target, signaling intermediate)\", \"Whether this antiviral role generalizes beyond PRRSV not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Mapping a 24-amino-acid region in DDX10 that recruits NOL10 as a critical cofactor for NUP98::DDX10-driven leukemia, with downstream regulation of serine biosynthesis and ATF4 mRNA stability, provided the most detailed mechanistic dissection of the fusion oncoprotein to date.\",\n      \"evidence\": \"Domain deletion/mutagenesis, Co-IP with NOL10, Nol10 knockout mouse leukemia model, mRNA stability assays\",\n      \"pmids\": [\"40263434\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NOL10 interaction reflects a normal DDX10 function or is neomorphic in the fusion context unclear\", \"Structural basis of the 24-amino-acid–NOL10 interaction not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"DDX10 was shown to undergo liquid-liquid phase separation with Rab27b, regulating exosomal PD-L1 secretion and thereby modulating anti-tumor immune responses, extending DDX10 function to exosome biology and immune evasion.\",\n      \"evidence\": \"Phase separation assay, Co-IP, exosome quantification, PD-L1 measurement, T cell functional assays in oral squamous cell carcinoma cells\",\n      \"pmids\": [\"40352946\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phase separation properties of DDX10 alone not characterized biophysically\", \"Whether RNA helicase activity is required for the Rab27b interaction and phase separation unknown\", \"Single lab study\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the direct RNA substrates of human DDX10 in ribosome biogenesis and immune signaling, the structural basis of DDX10 within the SSU processome, and the mechanism by which DDX10 promotes type I interferon production.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No in vitro reconstitution of DDX10 helicase activity on physiological RNA substrates\", \"No high-resolution structure of DDX10 in any complex\", \"Mechanism linking DDX10 to IFN-β transcription or signaling pathway unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 3, 4, 5]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 2, 5]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [9, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [3, 4, 5, 6]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [9, 10]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 2, 11]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [9, 13]}\n    ],\n    \"complexes\": [\n      \"SSU processome (90S pre-ribosome)\",\n      \"U14 snoRNP-containing 50S complex\"\n    ],\n    \"partners\": [\n      \"NUP98\",\n      \"NOL10\",\n      \"AIM2\",\n      \"SQSTM1\",\n      \"FBL\",\n      \"RAB27B\",\n      \"RPL35\",\n      \"IMP4\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}