{"gene":"DDX24","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":2000,"finding":"DDX24 was cloned and characterized as a DEAD-box protein containing all conserved DEAD-box motifs; it is ubiquitously expressed across human tissues and localized to human chromosome 14q32.","method":"cDNA cloning, Northern blot analysis, radiation hybrid mapping, genomic sequence analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cloning and characterization with multiple orthogonal methods (sequence, expression, mapping), single lab","pmids":["10936056"],"is_preprint":false},{"year":2008,"finding":"DDX24 knockdown inhibits HIV-1 RNA packaging and viral infectivity specifically in the context of Rev/RRE-dependent (but not CTE-dependent) nuclear export of viral RNA, and DDX24 physically interacts with the HIV-1 Rev protein.","method":"siRNA knockdown, viral infectivity assays, RNA packaging assays, co-immunoprecipitation (DDX24–Rev interaction)","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction shown, functional readout with mechanistic specificity (Rev/RRE vs CTE), single lab","pmids":["18289627"],"is_preprint":false},{"year":2013,"finding":"DDX24 negatively regulates RIG-I-like receptor (RLR)-mediated innate immune signaling by associating with adaptor proteins FADD and RIP1, preferentially impeding IRF7 activity; DDX24 preferentially binds RNA over DNA, and its loss augments cytosolic RNA-mediated innate signaling.","method":"Overexpression and siRNA knockdown assays, co-immunoprecipitation (DDX24–FADD, DDX24–RIP1), IRF7 reporter assays, RNA/DNA binding assays, embryonic lethality phenotype upon DDX24 loss","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, functional reporter assays, loss-of-function phenotype, multiple orthogonal methods, replicated direction of regulation","pmids":["24204270"],"is_preprint":false},{"year":2014,"finding":"MDM2 interacts with DDX24 via its central region and mediates non-proteolytic polyubiquitylation of DDX24 both in vitro and in vivo; this polyubiquitylation promotes DDX24 association with pre-ribosomal ribonucleoprotein (pre-rRNP) processing complexes required for early pre-rRNA processing. Depletion of DDX24 impairs pre-rRNA processing, abrogates MDM2 function, and leads to p53 stabilization.","method":"Co-immunoprecipitation, in vitro and in vivo ubiquitylation assays, siRNA knockdown, pre-rRNA processing assays, p53 stabilization assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of ubiquitylation, reciprocal Co-IP, functional pre-rRNA processing readout, multiple orthogonal methods in one study","pmids":["24980433"],"is_preprint":false},{"year":2015,"finding":"DDX24 interacts with p300 and suppresses p300-mediated acetylation of p53, thereby inhibiting p53 transcriptional targets (p21, PUMA). DDX24 knockdown increases p53 acetylation and promotes p53-dependent cell cycle arrest and senescence.","method":"Co-immunoprecipitation (DDX24–p300), acetylation assays, siRNA knockdown, p53 target gene expression analysis, cell cycle and senescence assays","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, direct acetylation functional assay, loss-of-function with defined p53-dependent phenotype, multiple orthogonal methods","pmids":["25867071"],"is_preprint":false},{"year":2019,"finding":"Point mutations in DDX24 (including ones in the ATP-binding domain) are associated with vascular malformations; DDX24 knockdown in endothelial cells results in elevated migration and tube formation, indicating a role for DDX24 in suppressing endothelial cell function.","method":"Genetic sequencing, structural modeling, siRNA knockdown, endothelial cell migration and tube formation assays, transcriptomic analysis","journal":"Hepatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct knockdown with defined cellular phenotype, structural modeling, but functional mechanism not fully resolved at molecular level","pmids":["30063812"],"is_preprint":false},{"year":2022,"finding":"DDX24 binds the mRNA of LAMB1 (at nucleotides 618–624) and stabilizes it in a manner dependent on interaction between nucleolin and the C-terminal region of DDX24, thereby promoting HCC migration and proliferation.","method":"RNA immunoprecipitation, mRNA stability assays, co-immunoprecipitation (DDX24–nucleolin), overexpression and knockdown, in vivo xenograft","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA-IP with defined binding site, mRNA stability assay, protein interaction confirmed, single lab","pmids":["35763670"],"is_preprint":false},{"year":2022,"finding":"DDX24 interacts with RPL5 and promotes its ubiquitination and degradation, thereby promoting NSCLC metastasis.","method":"Co-immunoprecipitation followed by mass spectrometry, ubiquitination assays, protein stability assays, Transwell/wound-healing assays, in vivo xenograft","journal":"Cancer medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP/MS identification confirmed by follow-up, ubiquitination assay, single lab","pmids":["35864588"],"is_preprint":false},{"year":2022,"finding":"DDX24 and DDX49 bind predominantly immediate-early and early KSHV mRNAs (identified by RNA immunoprecipitation followed by next-generation sequencing) and their overexpression suppresses KSHV lytic reactivation, reducing viral gene transcription and genome replication.","method":"RNA immunoprecipitation sequencing (RIP-seq), overexpression studies, KSHV lytic reactivation assays, interferon induction assays","journal":"Viruses","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP-seq identifies binding targets, functional lytic reactivation readout, single lab","pmids":["36298642"],"is_preprint":false},{"year":2022,"finding":"DDX24 is enriched in planarian muscles; its knockdown disrupts muscle fiber organization, leading to defective pole specification and misregulation of positional control genes during regeneration, and upregulates wound-induced Wnt signaling. Suppressing ectopic Wnt activity rescues the knockdown phenotype.","method":"RNAi knockdown, immunofluorescence, genetic epistasis (Wnt inhibition rescuing DDX24-KD phenotype), in situ hybridization","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with phenotypic rescue, direct localization, single lab using planarian model","pmids":["35523320"],"is_preprint":false},{"year":2022,"finding":"LINC02551 acts as a molecular adaptor that blocks the interaction between DDX24 and the E3 ligase TRIM27, thereby preventing ubiquitination and degradation of DDX24.","method":"Co-immunoprecipitation, ubiquitination assays, RNA pulldown, lincRNA knockdown/overexpression","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP and ubiquitination assays demonstrate mechanism, single lab","pmids":["36335087"],"is_preprint":false},{"year":2022,"finding":"DDX24 mutations K11E and E271K represent loss-of-function for cell proliferation; cells expressing these mutants show decreased nucleoli number, slower proliferation, and lower colony formation rates compared to wild-type DDX24.","method":"Stable cell line construction, immunofluorescence (nucleoli counting), proliferation and colony formation assays, in vivo tumor-bearing mouse model with 18F-FDG PET/CT, transcriptome sequencing","journal":"International journal of medical sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays in vitro and in vivo, two independent mutations tested, single lab","pmids":["35370459"],"is_preprint":false},{"year":2023,"finding":"DDX24 is mainly located in the nucleolus; disease-associated mutant DDX24-E271K partitions less into nucleoli in patient tissues and endothelial cells, altering nucleolar morphology. DDX24 physically associates with NPM1 and regulates its liquid-liquid phase separation behavior as a client in the nucleolar granular component. DDX24 mutation or knockdown disrupts ribosome biogenesis and elevates endothelial cell migration and tube formation.","method":"In vitro condensate assay (LLPS), co-immunoprecipitation (DDX24–NPM1), immunofluorescence in patient tissues and cultured endothelial cells, siRNA knockdown, ribosome biogenesis assay, migration and tube formation assays","journal":"International journal of biological sciences","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of phase separation, Co-IP, patient tissue validation, multiple orthogonal methods in one study","pmids":["37705750"],"is_preprint":false},{"year":2023,"finding":"DDX24 binds FANCA mRNA and stabilizes it, promoting VSMC proliferation and cell cycle progression. VSMC-specific Ddx24 knockout mice die before embryonic day 13.5 with vascular defects; FANCA overexpression rescues cell cycle and DNA repair defects caused by DDX24 deficiency.","method":"Conditional knockout mice (Tagln-Cre), RNA immunoprecipitation with qRT-PCR, RNA pulldown, mRNA stability assays, RNA sequencing, flow cytometry, cell proliferation assays, rescue experiments","journal":"Arteriosclerosis, thrombosis, and vascular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — RNA-IP and RNA pulldown, conditional knockout in vivo, genetic rescue, multiple orthogonal methods","pmids":["37470182"],"is_preprint":false},{"year":2023,"finding":"DDX24 binds HK1 mRNA and positively regulates HK1 expression, promoting glycolysis (glucose uptake and lactate production) in gastric cancer cells.","method":"RNA immunoprecipitation, glucose uptake and lactate production assays, DDX24 overexpression/knockdown, cell proliferation and migration assays","journal":"Cellular signalling","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/RIP, limited mechanistic follow-up, single lab","pmids":["38043669"],"is_preprint":false},{"year":2024,"finding":"Endothelium-targeted Ddx24 conditional knockout mice show no developmental abnormality but exhibit vascular hyperpermeability upon ConA challenge, exacerbating immune-mediated hepatitis via upregulation of TNF-α and IFN-γ and downregulation of vascular integrity-associated proteins.","method":"CRISPR/Cas9-mediated Cre-loxP conditional knockout mice, mass spectrometry of liver proteins, endothelial migration and tube formation assays, in vivo ConA hepatitis model, cytokine measurement","journal":"International immunopharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockout with defined vascular permeability phenotype and proteomic identification, single lab","pmids":["38354508"],"is_preprint":false},{"year":2025,"finding":"DDX24 deficiency in zebrafish enhances VEGFR2 expression by directly binding to its mRNA in non-brain endothelial cells, while suppressing GPR124/RECK-mediated Wnt signaling in brain endothelial cells, causing spatially distinct angiogenesis phenotypes (intersegmental vessel hyperbranching vs. inhibited central artery angiogenesis).","method":"Zebrafish DDX24 knockout, RNA binding assays (mRNA binding), spatial transcriptomics, pharmacological rescue experiments, in vivo imaging","journal":"PNAS","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vivo genetic model, direct mRNA binding, pharmacological epistasis rescue, spatial transcriptomics, multiple orthogonal methods","pmids":["40339127"],"is_preprint":false},{"year":2025,"finding":"DDX24 binds PPFIA4 mRNA and enhances its stability in cerebral microvascular endothelial cells; PPFIA4 knockdown impairs mitochondrial homeostasis and barrier function. Endothelial-specific Ddx24 knockout mice show increased BBB permeability and learning/memory deficits. DDX24 knockdown causes occludin phosphorylation and mitochondrial dysfunction, reversed by NADPH oxidase inhibition.","method":"Endothelial-specific Ddx24 conditional knockout mice, RNA immunoprecipitation (DDX24–PPFIA4 mRNA), mRNA stability assay, occludin phosphorylation assay, BBB permeability assay, behavioral tests, pharmacological NADPH oxidase inhibition","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — conditional KO in vivo with behavioral phenotype, RNA-IP, mRNA stability, pharmacological epistasis, multiple orthogonal methods","pmids":["41105514"],"is_preprint":false},{"year":2025,"finding":"DDX24 functions as a splicing factor that directly binds IKBKG pre-mRNA; DDX24 ablation stimulates generation of the long splicing isoform of IKBKG, which promotes autophagy through NF-κB signaling and BECN1 transcription, thereby suppressing lung cancer growth.","method":"Mass spectrometry, RNA sequencing (alternative splicing analysis), co-immunoprecipitation, luciferase reporter assays, functional rescue experiments, xenograft tumor models","journal":"Theranostics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding and splicing outcome identified, luciferase reporter, functional rescue, single lab","pmids":["39897555"],"is_preprint":false},{"year":2025,"finding":"DDX24 regulates transcription of heme oxygenase-1 (HO-1) at the promoter/enhancer E1 region level (not by mRNA stability), thereby exerting anti-apoptotic and anti-oxidative effects under oxidative stress conditions.","method":"RNA sequencing, DDX24 knockdown and overexpression, HO-1 expression and mRNA stability assays, promoter/enhancer reporter assay, cell viability assays","journal":"FASEB journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — transcriptional regulation inferred from reporter and expression assays, mechanism at promoter level not fully resolved, single lab","pmids":["40847746"],"is_preprint":false},{"year":2026,"finding":"DDX24 promotes mRNA decay of CLEC14A and ERG mRNAs in endothelial cells by directly binding these transcripts and promoting their degradation in a CCR4-NOT deadenylase complex-dependent manner, thereby modulating endothelial cell functions critical for angiogenesis.","method":"Infrared cross-linking immunoprecipitation sequencing (irCLIP-seq), mRNA stability assays, co-immunoprecipitation (DDX24–CCR4-NOT complex), endothelial cell functional assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — irCLIP-seq identifies direct binding sites, Co-IP links DDX24 to CCR4-NOT complex, mRNA stability assays confirm mechanism, multiple orthogonal methods","pmids":["41728947"],"is_preprint":false},{"year":2026,"finding":"SNRPF-mediated splicing controls DDX24 protein abundance: SNRPF depletion induces intron 6 retention in DDX24 pre-mRNA, disrupting the Helicase_C domain and generating premature termination codons that trigger nonsense-mediated decay (NMD), reducing DDX24 protein levels.","method":"Integrated transcriptomic and proteomic analyses, intron retention analysis, antisense oligonucleotide experiments, NMD pathway validation, xenograft models","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — splicing event identified by transcriptomics, functional NMD mechanism proposed and supported, multiple methods, single lab","pmids":["42107058"],"is_preprint":false}],"current_model":"DDX24 is a nucleolar DEAD-box RNA helicase that directly binds specific mRNAs (LAMB1, FANCA, VEGFR2, PPFIA4, HK1, IKBKG pre-mRNA, CLEC14A, ERG) to regulate their stability or splicing; it associates with the CCR4-NOT deadenylase complex to promote mRNA decay, participates in pre-rRNA processing via MDM2-mediated non-proteolytic polyubiquitylation, suppresses RLR innate immune signaling by interacting with FADD and RIP1 to impede IRF7, inhibits p300-mediated p53 acetylation by binding p300, interacts with NPM1 to regulate nucleolar phase separation and ribosome biogenesis, and is subject to proteolytic control via TRIM27-mediated ubiquitination that is blocked by lincRNA LINC02551."},"narrative":{"mechanistic_narrative":"DDX24 is a ubiquitously expressed nucleolar DEAD-box RNA helicase that integrates ribosome biogenesis with post-transcriptional control of specific mRNAs governing cell proliferation, vascular biology, and innate immunity [PMID:10936056, PMID:24980433, PMID:37705750]. In the nucleolus it associates with NPM1 to regulate liquid-liquid phase separation of the granular component and supports ribosome biogenesis, with disease-associated mutations disrupting nucleolar partitioning and morphology [PMID:37705750]; its incorporation into pre-rRNP processing complexes for early pre-rRNA processing requires MDM2-mediated non-proteolytic polyubiquitylation, and DDX24 loss impairs pre-rRNA processing and stabilizes p53 [PMID:24980433]. DDX24 also restrains the p53 pathway directly by binding p300 and suppressing p300-mediated p53 acetylation [PMID:25867071]. As a sequence-specific RNA-binding protein, DDX24 directly binds and stabilizes target transcripts including LAMB1, FANCA, and PPFIA4 [PMID:35763670, PMID:37470182, PMID:41105514], promotes decay of CLEC14A and ERG mRNAs through the CCR4-NOT deadenylase complex [PMID:41728947], and acts as a splicing factor on IKBKG pre-mRNA [PMID:39897555]; through these targets and direct binding of VEGFR2 mRNA it controls endothelial migration, tube formation, angiogenesis, and blood-brain-barrier integrity, and point mutations in DDX24 (including the ATP-binding domain) are associated with vascular malformations [PMID:30063812, PMID:37470182, PMID:40339127, PMID:41105514]. In innate immunity DDX24 negatively regulates RIG-I-like receptor signaling by associating with FADD and RIP1 to impede IRF7 [PMID:24204270]. DDX24 abundance is itself controlled post-translationally by TRIM27-mediated ubiquitination, which is blocked by LINC02551, and by SNRPF-dependent splicing that prevents NMD of its transcript [PMID:36335087, PMID:42107058].","teleology":[{"year":2000,"claim":"Established DDX24 as a bona fide DEAD-box helicase family member, defining the molecular class and chromosomal locus before any function was known.","evidence":"cDNA cloning, Northern blot, and radiation hybrid mapping of the human gene","pmids":["10936056"],"confidence":"Medium","gaps":["No enzymatic helicase activity demonstrated","No cellular function or RNA targets identified","Localization not yet resolved"]},{"year":2008,"claim":"First functional link to RNA metabolism, showing DDX24 acts in Rev/RRE-dependent viral RNA export via direct interaction with HIV-1 Rev.","evidence":"siRNA knockdown, viral packaging/infectivity assays, and Co-IP in human cells","pmids":["18289627"],"confidence":"Medium","gaps":["Endogenous host RNA targets not addressed","Mechanism of export specificity unresolved"]},{"year":2013,"claim":"Defined DDX24 as a negative regulator of RLR innate immune signaling, connecting it to FADD/RIP1 adaptors and IRF7 suppression and demonstrating an essential developmental role.","evidence":"Reciprocal Co-IP, IRF7 reporter assays, RNA/DNA binding, and embryonic lethality on loss","pmids":["24204270"],"confidence":"High","gaps":["Helicase catalytic requirement for immune suppression not tested","Direct RNA substrates in this pathway unknown"]},{"year":2014,"claim":"Placed DDX24 in nucleolar pre-rRNA processing and the MDM2-p53 axis, showing MDM2 non-proteolytically polyubiquitylates DDX24 to enable its recruitment to pre-rRNP complexes.","evidence":"In vitro/in vivo ubiquitylation, Co-IP, pre-rRNA processing and p53 stabilization assays","pmids":["24980433"],"confidence":"High","gaps":["Ubiquitin chain linkage type not fully defined","Which pre-rRNA processing step DDX24 catalyzes unresolved"]},{"year":2015,"claim":"Identified a second, ribosome-independent route by which DDX24 restrains p53: direct p300 binding to block p53 acetylation and dampen p53 target transcription.","evidence":"Reciprocal Co-IP, acetylation assays, knockdown with cell cycle/senescence readouts","pmids":["25867071"],"confidence":"High","gaps":["Whether RNA binding is required for p300 inhibition unknown","Structural basis of DDX24-p300 contact undefined"]},{"year":2019,"claim":"Linked DDX24 point mutations, including ATP-binding-domain residues, to human vascular malformations and to suppression of endothelial migration/tube formation.","evidence":"Genetic sequencing, structural modeling, endothelial knockdown functional assays","pmids":["30063812"],"confidence":"Medium","gaps":["Molecular mechanism connecting mutation to endothelial phenotype not resolved","Causal RNA targets not identified"]},{"year":2022,"claim":"Established DDX24 as a sequence-specific mRNA-stabilizing factor and a regulator of ribosomal protein turnover, with targets driving cancer phenotypes.","evidence":"RNA-IP with defined binding sites, mRNA stability assays, Co-IP with nucleolin and RPL5, ubiquitination/stability assays, xenografts","pmids":["35763670","35864588"],"confidence":"Medium","gaps":["How DDX24 selects target transcripts not defined","Helicase activity contribution to stabilization untested"]},{"year":2022,"claim":"Showed DDX24 protein level is controlled by TRIM27-mediated ubiquitination, antagonized by LINC02551 acting as a decoy adaptor.","evidence":"Co-IP, ubiquitination assays, RNA pulldown, lincRNA gain/loss","pmids":["36335087"],"confidence":"Medium","gaps":["TRIM27 ubiquitination site on DDX24 not mapped","Physiological contexts triggering this control unknown"]},{"year":2022,"claim":"Demonstrated DDX24 binds viral immediate-early/early mRNAs and suppresses KSHV lytic reactivation, and that conserved residues support proliferation, broadening its antiviral and growth roles.","evidence":"RIP-seq, lytic reactivation assays; mutant cell lines with proliferation/nucleoli readouts; planarian RNAi epistasis","pmids":["36298642","35370459","35523320"],"confidence":"Medium","gaps":["Mechanism linking viral mRNA binding to transcription suppression unclear","Conserved-residue mutants' biochemical defects undefined"]},{"year":2023,"claim":"Resolved a nucleolar phase-separation function via NPM1 and a vascular mRNA-stabilization program via FANCA, connecting ribosome biogenesis defects to endothelial/VSMC pathology.","evidence":"In vitro LLPS, Co-IP with NPM1, patient-tissue IF; conditional Ddx24 knockout mice, RNA-IP/pulldown, FANCA rescue","pmids":["37705750","37470182"],"confidence":"High","gaps":["How mutations alter NPM1 client behavior mechanistically unresolved","Relationship between rRNA and mRNA functions not unified"]},{"year":2025,"claim":"Expanded the direct mRNA-target repertoire and tissue contexts, defining VEGFR2-binding-driven angiogenesis, PPFIA4-stabilization-driven BBB integrity, and IKBKG pre-mRNA splicing control of autophagy.","evidence":"Zebrafish and endothelial-specific knockout models, RNA-IP/binding assays, spatial transcriptomics, splicing analysis, pharmacological epistasis","pmids":["40339127","41105514","39897555"],"confidence":"High","gaps":["Determinants of target-specific stabilization vs splicing outcomes unknown","Whether helicase catalysis is required across these targets untested"]},{"year":2026,"claim":"Defined a decay arm of DDX24 function, linking direct binding of CLEC14A/ERG mRNAs to the CCR4-NOT deadenylase complex, and showed DDX24 abundance is gated by SNRPF-dependent splicing/NMD.","evidence":"irCLIP-seq, mRNA stability assays, Co-IP with CCR4-NOT; transcriptomic intron-retention and NMD analyses with ASOs","pmids":["41728947","42107058"],"confidence":"High","gaps":["What switches DDX24 between stabilizing and destabilizing modes is unknown","Recruitment mechanism to CCR4-NOT on specific transcripts undefined"]},{"year":null,"claim":"How a single helicase reconciles opposing post-transcriptional outcomes (mRNA stabilization, decay via CCR4-NOT, and splicing) on different targets, and whether its catalytic ATPase/helicase activity drives these, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct demonstration of ATP-dependent helicase activity on target RNAs","No unifying rule for target selection or outcome","No structural model of DDX24-RNA or DDX24-complex assemblies"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2,6,13,16,17,20]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[18,20]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,2]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[3,12]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,20,18]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[3,12]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[13,16,17]}],"complexes":["CCR4-NOT deadenylase complex","pre-ribosomal ribonucleoprotein (pre-rRNP) processing complex"],"partners":["NPM1","MDM2","EP300","FADD","RIPK1","TRIM27","RPL5","NCL"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9GZR7","full_name":"ATP-dependent RNA helicase DDX24","aliases":["DEAD box protein 24"],"length_aa":859,"mass_kda":96.3,"function":"ATP-dependent RNA helicase that plays a role in various aspects of RNA metabolism including pre-mRNA splicing and is thereby involved in different biological processes such as cell cycle regulation or innate immunity (PubMed:24204270, PubMed:24980433). Plays an inhibitory role in TP53 transcriptional activity and subsequently in TP53 controlled cell growth arrest and senescence by inhibiting its EP300 mediated acetylation (PubMed:25867071). Negatively regulates cytosolic RNA-mediated innate immune signaling at least in part by affecting RIPK1/IRF7 interactions. Alternatively, possesses antiviral activity by recognizing gammaherpesvirus transcripts in the context of lytic reactivation (PubMed:36298642). Plays an essential role in cell cycle regulation in vascular smooth muscle cells by interacting with and regulating FANCA (Fanconi anemia complementation group A) mRNA (By similarity) (Microbial infection) Plays a positive role in HIV-1 infection by promoting Rev-dependent nuclear export of viral RNAs and their packaging into virus particles (PubMed:24204270)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9GZR7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DDX24","classification":"Common Essential","n_dependent_lines":1152,"n_total_lines":1208,"dependency_fraction":0.9536423841059603},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CSNK2B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DDX24","total_profiled":1310},"omim":[{"mim_id":"606181","title":"DEAD-BOX HELICASE 24; DDX24","url":"https://www.omim.org/entry/606181"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DDX24"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9GZR7","domains":[{"cath_id":"3.40.50.300","chopping":"185-263_385-520_528-555","consensus_level":"medium","plddt":83.4409,"start":185,"end":555},{"cath_id":"3.40.50.300","chopping":"564-715","consensus_level":"high","plddt":88.8796,"start":564,"end":715},{"cath_id":"1.20.58","chopping":"727-798","consensus_level":"high","plddt":86.5883,"start":727,"end":798}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZR7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZR7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9GZR7-F1-predicted_aligned_error_v6.png","plddt_mean":64.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DDX24","jax_strain_url":"https://www.jax.org/strain/search?query=DDX24"},"sequence":{"accession":"Q9GZR7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9GZR7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9GZR7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9GZR7"}},"corpus_meta":[{"pmid":"24204270","id":"PMC_24204270","title":"DDX24 negatively regulates cytosolic RNA-mediated innate immune signaling.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/24204270","citation_count":76,"is_preprint":false},{"pmid":"18289627","id":"PMC_18289627","title":"The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA.","date":"2008","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/18289627","citation_count":51,"is_preprint":false},{"pmid":"25867071","id":"PMC_25867071","title":"Negative regulation of the p300-p53 interplay by DDX24.","date":"2015","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/25867071","citation_count":43,"is_preprint":false},{"pmid":"36335087","id":"PMC_36335087","title":"ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/36335087","citation_count":43,"is_preprint":false},{"pmid":"35763670","id":"PMC_35763670","title":"RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression.","date":"2022","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35763670","citation_count":30,"is_preprint":false},{"pmid":"24980433","id":"PMC_24980433","title":"MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24.","date":"2014","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/24980433","citation_count":19,"is_preprint":false},{"pmid":"30063812","id":"PMC_30063812","title":"DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera.","date":"2019","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/30063812","citation_count":17,"is_preprint":false},{"pmid":"35864588","id":"PMC_35864588","title":"DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer.","date":"2022","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35864588","citation_count":15,"is_preprint":false},{"pmid":"10936056","id":"PMC_10936056","title":"Cloning and characterization of human DDX24 and mouse Ddx24, two novel putative DEAD-Box proteins, and mapping DDX24 to human chromosome 14q32.","date":"2000","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10936056","citation_count":14,"is_preprint":false},{"pmid":"37705750","id":"PMC_37705750","title":"DDX24 Mutation Alters NPM1 Phase Behavior and Disrupts Nucleolar Homeostasis in Vascular Malformations.","date":"2023","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37705750","citation_count":10,"is_preprint":false},{"pmid":"37470182","id":"PMC_37470182","title":"DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA.","date":"2023","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/37470182","citation_count":10,"is_preprint":false},{"pmid":"39897555","id":"PMC_39897555","title":"Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy.","date":"2025","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/39897555","citation_count":8,"is_preprint":false},{"pmid":"38043669","id":"PMC_38043669","title":"DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer.","date":"2023","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/38043669","citation_count":8,"is_preprint":false},{"pmid":"36298642","id":"PMC_36298642","title":"DExD/H Box Helicases DDX24 and DDX49 Inhibit Reactivation of Kaposi's Sarcoma Associated Herpesvirus by Interacting with Viral mRNAs.","date":"2022","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/36298642","citation_count":7,"is_preprint":false},{"pmid":"35523320","id":"PMC_35523320","title":"DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration.","date":"2022","source":"Developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35523320","citation_count":6,"is_preprint":false},{"pmid":"40339127","id":"PMC_40339127","title":"DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis.","date":"2025","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/40339127","citation_count":5,"is_preprint":false},{"pmid":"36310384","id":"PMC_36310384","title":"DDX24 regulates the chemosensitivity of hepatocellular carcinoma to sorafenib via mediating the expression of SNORA18.","date":"2022","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/36310384","citation_count":4,"is_preprint":false},{"pmid":"35370459","id":"PMC_35370459","title":"Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity.","date":"2022","source":"International journal of medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35370459","citation_count":3,"is_preprint":false},{"pmid":"38354508","id":"PMC_38354508","title":"Endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice due to vascular hyper-permeability.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38354508","citation_count":1,"is_preprint":false},{"pmid":"40216172","id":"PMC_40216172","title":"DDX24 inhibits clear cell renal cell carcinoma progression by directly regulating AKR1B10.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/40216172","citation_count":0,"is_preprint":false},{"pmid":"41105514","id":"PMC_41105514","title":"DEAD-box helicase DDX24 is essential for endothelial mitochondrial function to maintain the blood-brain barrier.","date":"2025","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/41105514","citation_count":0,"is_preprint":false},{"pmid":"41952180","id":"PMC_41952180","title":"CSTA and DDX24: potential biomarkers regulating ferroptosis in sepsis and their diagnostic value.","date":"2026","source":"BMC medical genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41952180","citation_count":0,"is_preprint":false},{"pmid":"40847746","id":"PMC_40847746","title":"Anti-Apoptotic and Anti-Oxidative Effects of DDX24 Through HO-1 Transcriptional Regulation.","date":"2025","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/40847746","citation_count":0,"is_preprint":false},{"pmid":"42208160","id":"PMC_42208160","title":"DDX24 exacerbates inflammation-induced immunosuppression in oral squamous cell carcinoma progression through IL-17 signaling pathway.","date":"2026","source":"Archives of oral biology","url":"https://pubmed.ncbi.nlm.nih.gov/42208160","citation_count":0,"is_preprint":false},{"pmid":"41728947","id":"PMC_41728947","title":"DDX24 modulates angiogenesis by promoting CCR4-NOT complex-dependent mRNA decay.","date":"2026","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/41728947","citation_count":0,"is_preprint":false},{"pmid":"41948606","id":"PMC_41948606","title":"Immunomodulatory Roles and Clinical Significance of GZMM and DDX24 in Sepsis: A Multiomics Integrative Analysis With Experimental Validation.","date":"2026","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/41948606","citation_count":0,"is_preprint":false},{"pmid":"42107058","id":"PMC_42107058","title":"Disruption of the SNRPF-DDX24-E2F4 Feedback Loop Uncouples Splicing and Transcriptional Regulation to Suppress Ovarian Cancer Progression.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/42107058","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14586,"output_tokens":5200,"usd":0.060879,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13735,"output_tokens":4155,"usd":0.086275,"stage2_stop_reason":"end_turn"},"total_usd":0.147154,"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\": 2000,\n      \"finding\": \"DDX24 was cloned and characterized as a DEAD-box protein containing all conserved DEAD-box motifs; it is ubiquitously expressed across human tissues and localized to human chromosome 14q32.\",\n      \"method\": \"cDNA cloning, Northern blot analysis, radiation hybrid mapping, genomic sequence analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cloning and characterization with multiple orthogonal methods (sequence, expression, mapping), single lab\",\n      \"pmids\": [\"10936056\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"DDX24 knockdown inhibits HIV-1 RNA packaging and viral infectivity specifically in the context of Rev/RRE-dependent (but not CTE-dependent) nuclear export of viral RNA, and DDX24 physically interacts with the HIV-1 Rev protein.\",\n      \"method\": \"siRNA knockdown, viral infectivity assays, RNA packaging assays, co-immunoprecipitation (DDX24–Rev interaction)\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction shown, functional readout with mechanistic specificity (Rev/RRE vs CTE), single lab\",\n      \"pmids\": [\"18289627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"DDX24 negatively regulates RIG-I-like receptor (RLR)-mediated innate immune signaling by associating with adaptor proteins FADD and RIP1, preferentially impeding IRF7 activity; DDX24 preferentially binds RNA over DNA, and its loss augments cytosolic RNA-mediated innate signaling.\",\n      \"method\": \"Overexpression and siRNA knockdown assays, co-immunoprecipitation (DDX24–FADD, DDX24–RIP1), IRF7 reporter assays, RNA/DNA binding assays, embryonic lethality phenotype upon DDX24 loss\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, functional reporter assays, loss-of-function phenotype, multiple orthogonal methods, replicated direction of regulation\",\n      \"pmids\": [\"24204270\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"MDM2 interacts with DDX24 via its central region and mediates non-proteolytic polyubiquitylation of DDX24 both in vitro and in vivo; this polyubiquitylation promotes DDX24 association with pre-ribosomal ribonucleoprotein (pre-rRNP) processing complexes required for early pre-rRNA processing. Depletion of DDX24 impairs pre-rRNA processing, abrogates MDM2 function, and leads to p53 stabilization.\",\n      \"method\": \"Co-immunoprecipitation, in vitro and in vivo ubiquitylation assays, siRNA knockdown, pre-rRNA processing assays, p53 stabilization assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of ubiquitylation, reciprocal Co-IP, functional pre-rRNA processing readout, multiple orthogonal methods in one study\",\n      \"pmids\": [\"24980433\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"DDX24 interacts with p300 and suppresses p300-mediated acetylation of p53, thereby inhibiting p53 transcriptional targets (p21, PUMA). DDX24 knockdown increases p53 acetylation and promotes p53-dependent cell cycle arrest and senescence.\",\n      \"method\": \"Co-immunoprecipitation (DDX24–p300), acetylation assays, siRNA knockdown, p53 target gene expression analysis, cell cycle and senescence assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, direct acetylation functional assay, loss-of-function with defined p53-dependent phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"25867071\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Point mutations in DDX24 (including ones in the ATP-binding domain) are associated with vascular malformations; DDX24 knockdown in endothelial cells results in elevated migration and tube formation, indicating a role for DDX24 in suppressing endothelial cell function.\",\n      \"method\": \"Genetic sequencing, structural modeling, siRNA knockdown, endothelial cell migration and tube formation assays, transcriptomic analysis\",\n      \"journal\": \"Hepatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct knockdown with defined cellular phenotype, structural modeling, but functional mechanism not fully resolved at molecular level\",\n      \"pmids\": [\"30063812\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX24 binds the mRNA of LAMB1 (at nucleotides 618–624) and stabilizes it in a manner dependent on interaction between nucleolin and the C-terminal region of DDX24, thereby promoting HCC migration and proliferation.\",\n      \"method\": \"RNA immunoprecipitation, mRNA stability assays, co-immunoprecipitation (DDX24–nucleolin), overexpression and knockdown, in vivo xenograft\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA-IP with defined binding site, mRNA stability assay, protein interaction confirmed, single lab\",\n      \"pmids\": [\"35763670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX24 interacts with RPL5 and promotes its ubiquitination and degradation, thereby promoting NSCLC metastasis.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry, ubiquitination assays, protein stability assays, Transwell/wound-healing assays, in vivo xenograft\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP/MS identification confirmed by follow-up, ubiquitination assay, single lab\",\n      \"pmids\": [\"35864588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX24 and DDX49 bind predominantly immediate-early and early KSHV mRNAs (identified by RNA immunoprecipitation followed by next-generation sequencing) and their overexpression suppresses KSHV lytic reactivation, reducing viral gene transcription and genome replication.\",\n      \"method\": \"RNA immunoprecipitation sequencing (RIP-seq), overexpression studies, KSHV lytic reactivation assays, interferon induction assays\",\n      \"journal\": \"Viruses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP-seq identifies binding targets, functional lytic reactivation readout, single lab\",\n      \"pmids\": [\"36298642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX24 is enriched in planarian muscles; its knockdown disrupts muscle fiber organization, leading to defective pole specification and misregulation of positional control genes during regeneration, and upregulates wound-induced Wnt signaling. Suppressing ectopic Wnt activity rescues the knockdown phenotype.\",\n      \"method\": \"RNAi knockdown, immunofluorescence, genetic epistasis (Wnt inhibition rescuing DDX24-KD phenotype), in situ hybridization\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with phenotypic rescue, direct localization, single lab using planarian model\",\n      \"pmids\": [\"35523320\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LINC02551 acts as a molecular adaptor that blocks the interaction between DDX24 and the E3 ligase TRIM27, thereby preventing ubiquitination and degradation of DDX24.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, RNA pulldown, lincRNA knockdown/overexpression\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP and ubiquitination assays demonstrate mechanism, single lab\",\n      \"pmids\": [\"36335087\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DDX24 mutations K11E and E271K represent loss-of-function for cell proliferation; cells expressing these mutants show decreased nucleoli number, slower proliferation, and lower colony formation rates compared to wild-type DDX24.\",\n      \"method\": \"Stable cell line construction, immunofluorescence (nucleoli counting), proliferation and colony formation assays, in vivo tumor-bearing mouse model with 18F-FDG PET/CT, transcriptome sequencing\",\n      \"journal\": \"International journal of medical sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays in vitro and in vivo, two independent mutations tested, single lab\",\n      \"pmids\": [\"35370459\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DDX24 is mainly located in the nucleolus; disease-associated mutant DDX24-E271K partitions less into nucleoli in patient tissues and endothelial cells, altering nucleolar morphology. DDX24 physically associates with NPM1 and regulates its liquid-liquid phase separation behavior as a client in the nucleolar granular component. DDX24 mutation or knockdown disrupts ribosome biogenesis and elevates endothelial cell migration and tube formation.\",\n      \"method\": \"In vitro condensate assay (LLPS), co-immunoprecipitation (DDX24–NPM1), immunofluorescence in patient tissues and cultured endothelial cells, siRNA knockdown, ribosome biogenesis assay, migration and tube formation assays\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of phase separation, Co-IP, patient tissue validation, multiple orthogonal methods in one study\",\n      \"pmids\": [\"37705750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DDX24 binds FANCA mRNA and stabilizes it, promoting VSMC proliferation and cell cycle progression. VSMC-specific Ddx24 knockout mice die before embryonic day 13.5 with vascular defects; FANCA overexpression rescues cell cycle and DNA repair defects caused by DDX24 deficiency.\",\n      \"method\": \"Conditional knockout mice (Tagln-Cre), RNA immunoprecipitation with qRT-PCR, RNA pulldown, mRNA stability assays, RNA sequencing, flow cytometry, cell proliferation assays, rescue experiments\",\n      \"journal\": \"Arteriosclerosis, thrombosis, and vascular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — RNA-IP and RNA pulldown, conditional knockout in vivo, genetic rescue, multiple orthogonal methods\",\n      \"pmids\": [\"37470182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DDX24 binds HK1 mRNA and positively regulates HK1 expression, promoting glycolysis (glucose uptake and lactate production) in gastric cancer cells.\",\n      \"method\": \"RNA immunoprecipitation, glucose uptake and lactate production assays, DDX24 overexpression/knockdown, cell proliferation and migration assays\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/RIP, limited mechanistic follow-up, single lab\",\n      \"pmids\": [\"38043669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Endothelium-targeted Ddx24 conditional knockout mice show no developmental abnormality but exhibit vascular hyperpermeability upon ConA challenge, exacerbating immune-mediated hepatitis via upregulation of TNF-α and IFN-γ and downregulation of vascular integrity-associated proteins.\",\n      \"method\": \"CRISPR/Cas9-mediated Cre-loxP conditional knockout mice, mass spectrometry of liver proteins, endothelial migration and tube formation assays, in vivo ConA hepatitis model, cytokine measurement\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockout with defined vascular permeability phenotype and proteomic identification, single lab\",\n      \"pmids\": [\"38354508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX24 deficiency in zebrafish enhances VEGFR2 expression by directly binding to its mRNA in non-brain endothelial cells, while suppressing GPR124/RECK-mediated Wnt signaling in brain endothelial cells, causing spatially distinct angiogenesis phenotypes (intersegmental vessel hyperbranching vs. inhibited central artery angiogenesis).\",\n      \"method\": \"Zebrafish DDX24 knockout, RNA binding assays (mRNA binding), spatial transcriptomics, pharmacological rescue experiments, in vivo imaging\",\n      \"journal\": \"PNAS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vivo genetic model, direct mRNA binding, pharmacological epistasis rescue, spatial transcriptomics, multiple orthogonal methods\",\n      \"pmids\": [\"40339127\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX24 binds PPFIA4 mRNA and enhances its stability in cerebral microvascular endothelial cells; PPFIA4 knockdown impairs mitochondrial homeostasis and barrier function. Endothelial-specific Ddx24 knockout mice show increased BBB permeability and learning/memory deficits. DDX24 knockdown causes occludin phosphorylation and mitochondrial dysfunction, reversed by NADPH oxidase inhibition.\",\n      \"method\": \"Endothelial-specific Ddx24 conditional knockout mice, RNA immunoprecipitation (DDX24–PPFIA4 mRNA), mRNA stability assay, occludin phosphorylation assay, BBB permeability assay, behavioral tests, pharmacological NADPH oxidase inhibition\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — conditional KO in vivo with behavioral phenotype, RNA-IP, mRNA stability, pharmacological epistasis, multiple orthogonal methods\",\n      \"pmids\": [\"41105514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX24 functions as a splicing factor that directly binds IKBKG pre-mRNA; DDX24 ablation stimulates generation of the long splicing isoform of IKBKG, which promotes autophagy through NF-κB signaling and BECN1 transcription, thereby suppressing lung cancer growth.\",\n      \"method\": \"Mass spectrometry, RNA sequencing (alternative splicing analysis), co-immunoprecipitation, luciferase reporter assays, functional rescue experiments, xenograft tumor models\",\n      \"journal\": \"Theranostics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding and splicing outcome identified, luciferase reporter, functional rescue, single lab\",\n      \"pmids\": [\"39897555\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX24 regulates transcription of heme oxygenase-1 (HO-1) at the promoter/enhancer E1 region level (not by mRNA stability), thereby exerting anti-apoptotic and anti-oxidative effects under oxidative stress conditions.\",\n      \"method\": \"RNA sequencing, DDX24 knockdown and overexpression, HO-1 expression and mRNA stability assays, promoter/enhancer reporter assay, cell viability assays\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — transcriptional regulation inferred from reporter and expression assays, mechanism at promoter level not fully resolved, single lab\",\n      \"pmids\": [\"40847746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"DDX24 promotes mRNA decay of CLEC14A and ERG mRNAs in endothelial cells by directly binding these transcripts and promoting their degradation in a CCR4-NOT deadenylase complex-dependent manner, thereby modulating endothelial cell functions critical for angiogenesis.\",\n      \"method\": \"Infrared cross-linking immunoprecipitation sequencing (irCLIP-seq), mRNA stability assays, co-immunoprecipitation (DDX24–CCR4-NOT complex), endothelial cell functional assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — irCLIP-seq identifies direct binding sites, Co-IP links DDX24 to CCR4-NOT complex, mRNA stability assays confirm mechanism, multiple orthogonal methods\",\n      \"pmids\": [\"41728947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"SNRPF-mediated splicing controls DDX24 protein abundance: SNRPF depletion induces intron 6 retention in DDX24 pre-mRNA, disrupting the Helicase_C domain and generating premature termination codons that trigger nonsense-mediated decay (NMD), reducing DDX24 protein levels.\",\n      \"method\": \"Integrated transcriptomic and proteomic analyses, intron retention analysis, antisense oligonucleotide experiments, NMD pathway validation, xenograft models\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — splicing event identified by transcriptomics, functional NMD mechanism proposed and supported, multiple methods, single lab\",\n      \"pmids\": [\"42107058\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DDX24 is a nucleolar DEAD-box RNA helicase that directly binds specific mRNAs (LAMB1, FANCA, VEGFR2, PPFIA4, HK1, IKBKG pre-mRNA, CLEC14A, ERG) to regulate their stability or splicing; it associates with the CCR4-NOT deadenylase complex to promote mRNA decay, participates in pre-rRNA processing via MDM2-mediated non-proteolytic polyubiquitylation, suppresses RLR innate immune signaling by interacting with FADD and RIP1 to impede IRF7, inhibits p300-mediated p53 acetylation by binding p300, interacts with NPM1 to regulate nucleolar phase separation and ribosome biogenesis, and is subject to proteolytic control via TRIM27-mediated ubiquitination that is blocked by lincRNA LINC02551.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DDX24 is a ubiquitously expressed nucleolar DEAD-box RNA helicase that integrates ribosome biogenesis with post-transcriptional control of specific mRNAs governing cell proliferation, vascular biology, and innate immunity [#0, #3, #12]. In the nucleolus it associates with NPM1 to regulate liquid-liquid phase separation of the granular component and supports ribosome biogenesis, with disease-associated mutations disrupting nucleolar partitioning and morphology [#12]; its incorporation into pre-rRNP processing complexes for early pre-rRNA processing requires MDM2-mediated non-proteolytic polyubiquitylation, and DDX24 loss impairs pre-rRNA processing and stabilizes p53 [#3]. DDX24 also restrains the p53 pathway directly by binding p300 and suppressing p300-mediated p53 acetylation [#4]. As a sequence-specific RNA-binding protein, DDX24 directly binds and stabilizes target transcripts including LAMB1, FANCA, and PPFIA4 [#6, #13, #17], promotes decay of CLEC14A and ERG mRNAs through the CCR4-NOT deadenylase complex [#20], and acts as a splicing factor on IKBKG pre-mRNA [#18]; through these targets and direct binding of VEGFR2 mRNA it controls endothelial migration, tube formation, angiogenesis, and blood-brain-barrier integrity, and point mutations in DDX24 (including the ATP-binding domain) are associated with vascular malformations [#5, #13, #16, #17]. In innate immunity DDX24 negatively regulates RIG-I-like receptor signaling by associating with FADD and RIP1 to impede IRF7 [#2]. DDX24 abundance is itself controlled post-translationally by TRIM27-mediated ubiquitination, which is blocked by LINC02551, and by SNRPF-dependent splicing that prevents NMD of its transcript [#10, #21].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established DDX24 as a bona fide DEAD-box helicase family member, defining the molecular class and chromosomal locus before any function was known.\",\n      \"evidence\": \"cDNA cloning, Northern blot, and radiation hybrid mapping of the human gene\",\n      \"pmids\": [\"10936056\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No enzymatic helicase activity demonstrated\", \"No cellular function or RNA targets identified\", \"Localization not yet resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"First functional link to RNA metabolism, showing DDX24 acts in Rev/RRE-dependent viral RNA export via direct interaction with HIV-1 Rev.\",\n      \"evidence\": \"siRNA knockdown, viral packaging/infectivity assays, and Co-IP in human cells\",\n      \"pmids\": [\"18289627\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous host RNA targets not addressed\", \"Mechanism of export specificity unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined DDX24 as a negative regulator of RLR innate immune signaling, connecting it to FADD/RIP1 adaptors and IRF7 suppression and demonstrating an essential developmental role.\",\n      \"evidence\": \"Reciprocal Co-IP, IRF7 reporter assays, RNA/DNA binding, and embryonic lethality on loss\",\n      \"pmids\": [\"24204270\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Helicase catalytic requirement for immune suppression not tested\", \"Direct RNA substrates in this pathway unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Placed DDX24 in nucleolar pre-rRNA processing and the MDM2-p53 axis, showing MDM2 non-proteolytically polyubiquitylates DDX24 to enable its recruitment to pre-rRNP complexes.\",\n      \"evidence\": \"In vitro/in vivo ubiquitylation, Co-IP, pre-rRNA processing and p53 stabilization assays\",\n      \"pmids\": [\"24980433\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ubiquitin chain linkage type not fully defined\", \"Which pre-rRNA processing step DDX24 catalyzes unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identified a second, ribosome-independent route by which DDX24 restrains p53: direct p300 binding to block p53 acetylation and dampen p53 target transcription.\",\n      \"evidence\": \"Reciprocal Co-IP, acetylation assays, knockdown with cell cycle/senescence readouts\",\n      \"pmids\": [\"25867071\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RNA binding is required for p300 inhibition unknown\", \"Structural basis of DDX24-p300 contact undefined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked DDX24 point mutations, including ATP-binding-domain residues, to human vascular malformations and to suppression of endothelial migration/tube formation.\",\n      \"evidence\": \"Genetic sequencing, structural modeling, endothelial knockdown functional assays\",\n      \"pmids\": [\"30063812\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism connecting mutation to endothelial phenotype not resolved\", \"Causal RNA targets not identified\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established DDX24 as a sequence-specific mRNA-stabilizing factor and a regulator of ribosomal protein turnover, with targets driving cancer phenotypes.\",\n      \"evidence\": \"RNA-IP with defined binding sites, mRNA stability assays, Co-IP with nucleolin and RPL5, ubiquitination/stability assays, xenografts\",\n      \"pmids\": [\"35763670\", \"35864588\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How DDX24 selects target transcripts not defined\", \"Helicase activity contribution to stabilization untested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed DDX24 protein level is controlled by TRIM27-mediated ubiquitination, antagonized by LINC02551 acting as a decoy adaptor.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, RNA pulldown, lincRNA gain/loss\",\n      \"pmids\": [\"36335087\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"TRIM27 ubiquitination site on DDX24 not mapped\", \"Physiological contexts triggering this control unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrated DDX24 binds viral immediate-early/early mRNAs and suppresses KSHV lytic reactivation, and that conserved residues support proliferation, broadening its antiviral and growth roles.\",\n      \"evidence\": \"RIP-seq, lytic reactivation assays; mutant cell lines with proliferation/nucleoli readouts; planarian RNAi epistasis\",\n      \"pmids\": [\"36298642\", \"35370459\", \"35523320\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking viral mRNA binding to transcription suppression unclear\", \"Conserved-residue mutants' biochemical defects undefined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Resolved a nucleolar phase-separation function via NPM1 and a vascular mRNA-stabilization program via FANCA, connecting ribosome biogenesis defects to endothelial/VSMC pathology.\",\n      \"evidence\": \"In vitro LLPS, Co-IP with NPM1, patient-tissue IF; conditional Ddx24 knockout mice, RNA-IP/pulldown, FANCA rescue\",\n      \"pmids\": [\"37705750\", \"37470182\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How mutations alter NPM1 client behavior mechanistically unresolved\", \"Relationship between rRNA and mRNA functions not unified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Expanded the direct mRNA-target repertoire and tissue contexts, defining VEGFR2-binding-driven angiogenesis, PPFIA4-stabilization-driven BBB integrity, and IKBKG pre-mRNA splicing control of autophagy.\",\n      \"evidence\": \"Zebrafish and endothelial-specific knockout models, RNA-IP/binding assays, spatial transcriptomics, splicing analysis, pharmacological epistasis\",\n      \"pmids\": [\"40339127\", \"41105514\", \"39897555\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Determinants of target-specific stabilization vs splicing outcomes unknown\", \"Whether helicase catalysis is required across these targets untested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined a decay arm of DDX24 function, linking direct binding of CLEC14A/ERG mRNAs to the CCR4-NOT deadenylase complex, and showed DDX24 abundance is gated by SNRPF-dependent splicing/NMD.\",\n      \"evidence\": \"irCLIP-seq, mRNA stability assays, Co-IP with CCR4-NOT; transcriptomic intron-retention and NMD analyses with ASOs\",\n      \"pmids\": [\"41728947\", \"42107058\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"What switches DDX24 between stabilizing and destabilizing modes is unknown\", \"Recruitment mechanism to CCR4-NOT on specific transcripts undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single helicase reconciles opposing post-transcriptional outcomes (mRNA stabilization, decay via CCR4-NOT, and splicing) on different targets, and whether its catalytic ATPase/helicase activity drives these, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct demonstration of ATP-dependent helicase activity on target RNAs\", \"No unifying rule for target selection or outcome\", \"No structural model of DDX24-RNA or DDX24-complex assemblies\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2, 6, 13, 16, 17, 20]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [18, 20]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [3, 12]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 20, 18]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [3, 12]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [13, 16, 17]}\n    ],\n    \"complexes\": [\n      \"CCR4-NOT deadenylase complex\",\n      \"pre-ribosomal ribonucleoprotein (pre-rRNP) processing complex\"\n    ],\n    \"partners\": [\n      \"NPM1\",\n      \"MDM2\",\n      \"EP300\",\n      \"FADD\",\n      \"RIPK1\",\n      \"TRIM27\",\n      \"RPL5\",\n      \"NCL\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}