{"gene":"RDX","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2007,"finding":"Loss-of-function mutations in RDX (radixin) — including p.D578N affecting the actin-binding motif, p.A469fsX487 (frameshift), and p.Q155X truncating the FERM domain — segregate with autosomal recessive nonsyndromic sensorineural hearing loss (DFNB24) in consanguineous Pakistani families. High-resolution confocal microscopy in mouse inner ear demonstrated that radixin is expressed along the length of stereocilia of hair cells in the organ of Corti and vestibular system, establishing a direct role in stereocilia maintenance.","method":"Sanger sequencing of consanguineous families, domain-level mutation analysis predicting disruption of actin-binding motif and FERM domain, high-resolution confocal microscopy of mouse inner ear","journal":"Human mutation","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple independent disease-segregating mutations with domain-level mechanistic interpretation, replicated across two families plus original DFNB24 family, with direct localization by confocal microscopy in hair cells","pmids":["17226784"],"is_preprint":false},{"year":2014,"finding":"In Drosophila, the CUL3 adaptor RDX (Roadkill/HIB) directly interacts with the CENP-A loading factor CAL1. CAL1 is not itself a substrate but acts as an additional substrate-specifying factor for CUL3/RDX-mediated ubiquitylation of CENP-A. Crucially, CUL3/RDX-mediated ubiquitylation stabilizes rather than degrades CENP-A and CAL1; loss of RDX causes rapid degradation of both proteins and massive chromosome segregation defects.","method":"Co-immunoprecipitation, in vivo ubiquitylation assays, RNAi/genetic loss-of-function in Drosophila, immunofluorescence, epistasis analysis","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vivo ubiquitylation, genetic KD with clear cellular phenotype (chromosome segregation defects), multiple orthogonal methods in one study","pmids":["24636256"],"is_preprint":false},{"year":2015,"finding":"PKCη/Rdx (a parvovirus-induced kinase complex) phosphorylates mouse PDK1 at Ser138 (corresponding to human PDK1-pSer135), activating PDK1 independently of PI3-kinase signaling. This represents a novel intracellular loop-back mechanism whereby parvovirus-activated PKCη uses Rdx to sustain PDK1 activity and cancer cell survival.","method":"In vitro kinase assay, phospho-specific antibody detection, expression of constitutively active PDK1 mutant mimicking the phosphorylation, cell-based viral DNA amplification assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro kinase assay plus cell-based functional rescue with constitutively active PDK1 mimetic, single lab but two orthogonal approaches","pmids":["25742010"],"is_preprint":false},{"year":2012,"finding":"In Drosophila wing discs, Suppressor of fused (Su(fu)) controls a switch in Rdx (Roadkill) mechanism: in the absence of Su(fu) (strong Hh signal), Rdx blocks nuclear entry of Ci-155; in the presence of Su(fu) (moderate Hh), Rdx induces nuclear degradation of Ci-155. Strong Hh induces rdx and suppresses su(fu) expression; moderate Hh induces moderate rdx and high su(fu). This dual-mode action of Rdx fine-tunes Hh signaling output.","method":"Genetic epistasis in Drosophila wing discs, immunofluorescence for Ci-155 localization, in vivo expression analysis, loss-of-function and overexpression of rdx and su(fu)","journal":"Genes to cells : devoted to molecular & cellular mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with multiple allele combinations and direct protein localization readout, single lab","pmids":["23216924"],"is_preprint":false},{"year":2019,"finding":"Novel compound heterozygous variants in RDX (c.129_130del, p.His43Glnfs*28 and c.76_79del, p.Lys26*) were identified in a Chinese family with autosomal recessive nonsyndromic hearing loss, extending the mutational spectrum of DFNB24 and confirming the essential role of the radixin FERM domain N-terminus in auditory function.","method":"Next-generation sequencing of 227 known deafness genes, Sanger sequencing validation in family members","journal":"Molecular genetics & genomic medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — NGS with Sanger validation in a family, segregation confirmed, but mechanistic inference is by domain disruption prediction rather than direct functional assay","pmids":["31250571"],"is_preprint":false},{"year":2021,"finding":"miR-196b-5p directly targets RDX (radixin) mRNA, as confirmed by dual-luciferase reporter assay. Downregulation of miR-196b-5p increased RDX protein levels in ovarian granulosa cells, promoted apoptosis, inhibited proliferation, increased ROS production, and reduced estrogen synthesis (CYP19A1) and glucose uptake (GLUT4). Transfection with miR-196b-5p mimics reduced RDX levels and reversed these effects.","method":"Dual-luciferase reporter assay (direct target validation), RT-qPCR, Western blot, CCK8 proliferation assay, flow cytometry for apoptosis and ROS","journal":"Annals of translational medicine","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct miRNA-target validation by luciferase assay plus multiple cellular phenotype readouts, single lab","pmids":["35071469"],"is_preprint":false},{"year":2018,"finding":"miR-409-3p directly targets RDX (radixin) mRNA in tongue squamous cell carcinoma (TSCC), validated by dual-luciferase reporter assay. miR-409-3p mimic reduced RDX expression and suppressed proliferation, migration, and invasion of Tca8113 cells; miR-409-3p inhibitor increased RDX and enhanced these activities. si-RDX phenocopied miR-409-3p mimic and reversed the inhibitor effect, placing RDX downstream of miR-409-3p in regulating TSCC cell behavior. Tumor xenograft experiments confirmed that miR-409-3p mimic inhibited tumor growth and lymph node metastasis.","method":"Dual-luciferase reporter assay, RT-qPCR, Western blot, CCK-8, wound-healing, Transwell invasion assays, si-RNA knockdown, nude mouse xenograft","journal":"Oncology letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct target validation by luciferase plus multiple orthogonal cellular/in vivo assays, genetic epistasis via si-RDX rescue, single lab","pmids":["29928443"],"is_preprint":false}],"current_model":"Radixin (RDX/DFNB24) is an ERM-family protein that cross-links membrane proteins to the actin cytoskeleton via its FERM domain and C-terminal actin-binding motif; loss-of-function mutations in either domain cause autosomal recessive sensorineural hearing loss (DFNB24) through degeneration of inner ear hair cell stereocilia. In Drosophila, the orthologous Rdx/Roadkill serves as a CUL3 E3 ubiquitin ligase adaptor that stabilizes (rather than degrades) the centromeric histone CENP-A in a CAL1-dependent manner and, in the Hedgehog pathway, switches between blocking Ci-155 nuclear entry and promoting its nuclear degradation depending on Su(fu) levels. Additionally, PKCη/Rdx has been shown to directly phosphorylate PDK1-Ser138, activating it independently of PI3K, and RDX protein levels are post-translationally regulated by miR-196b-5p and miR-409-3p in granulosa cells and tongue squamous carcinoma cells, respectively."},"narrative":{"mechanistic_narrative":"RDX (radixin) is an actin-cytoskeleton-linking ERM-family protein whose integrity is essential for sensory hair cell function: loss-of-function mutations disrupting either its FERM domain or its C-terminal actin-binding motif segregate with autosomal recessive nonsyndromic sensorineural hearing loss (DFNB24), and radixin localizes along the length of hair cell stereocilia in the organ of Corti and vestibular system, indicating a direct structural role in stereocilia maintenance [PMID:17226784, PMID:31250571]. Studies of the Drosophila ortholog (Roadkill/HIB) reveal an independent function as a CUL3 E3 ubiquitin ligase substrate-specifying adaptor: in complex with CAL1 it ubiquitylates the centromeric histone CENP-A in a manner that stabilizes rather than degrades it, so that RDX loss triggers CENP-A/CAL1 degradation and chromosome segregation defects [PMID:24636256], and within Hedgehog signaling it acts in a Su(fu)-dependent dual mode, either blocking nuclear entry of Ci-155 or promoting its nuclear degradation to tune pathway output [PMID:23216924]. RDX has also been placed in a parvovirus-induced PKCη/Rdx kinase complex that phosphorylates PDK1 at Ser138 to activate it independently of PI3-kinase [PMID:25742010], and its protein abundance is post-transcriptionally controlled by direct miRNA targeting (miR-196b-5p in ovarian granulosa cells, miR-409-3p in tongue squamous carcinoma), where reducing RDX alters proliferation, apoptosis, migration, and invasion [PMID:35071469, PMID:29928443].","teleology":[{"year":2007,"claim":"Established that RDX is a human deafness gene and tied its function to stereocilia, answering whether radixin has a non-redundant physiological role in the inner ear.","evidence":"Sanger sequencing of consanguineous families identifying FERM-domain and actin-binding-motif mutations, with confocal localization in mouse inner ear","pmids":["17226784"],"confidence":"High","gaps":["Mechanism by which radixin loss leads to stereocilia degeneration not resolved at the molecular level","No direct biochemical assay of the disease mutations' effect on membrane-actin cross-linking"]},{"year":2012,"claim":"Resolved how the Drosophila ortholog can produce opposite effects on Hedgehog signaling, showing Su(fu) levels switch Rdx between blocking Ci-155 nuclear entry and promoting its nuclear degradation.","evidence":"Genetic epistasis and Ci-155 immunofluorescence localization in Drosophila wing discs with rdx/su(fu) loss- and gain-of-function","pmids":["23216924"],"confidence":"Medium","gaps":["Conducted in Drosophila; relevance to mammalian RDX not addressed","Biochemical basis of the Su(fu)-dependent switch not defined"]},{"year":2014,"claim":"Defined a CUL3-adaptor role for the ortholog in which ubiquitylation stabilizes rather than degrades its target, explaining how RDX maintains centromeric CENP-A.","evidence":"Reciprocal Co-IP, in vivo ubiquitylation assays, and RNAi/genetic loss-of-function with chromosome-segregation phenotyping in Drosophila","pmids":["24636256"],"confidence":"High","gaps":["Demonstrated in Drosophila; whether human RDX functions as a CUL3 adaptor is untested","Molecular basis for non-degradative ubiquitylation not defined"]},{"year":2015,"claim":"Implicated an Rdx-containing kinase complex in direct activation of PDK1, identifying a PI3K-independent route to PDK1 activity.","evidence":"In vitro kinase assay with phospho-specific detection plus cell-based rescue using a constitutively active PDK1 phosphomimetic","pmids":["25742010"],"confidence":"Medium","gaps":["Single lab; reciprocal validation and structural basis lacking","Direct kinase role attributed to PKCη/Rdx complex rather than RDX alone"]},{"year":2018,"claim":"Showed RDX abundance is directly controlled by miR-409-3p and that RDX acts downstream to drive tumor cell proliferation, migration, and invasion in tongue squamous carcinoma.","evidence":"Dual-luciferase target validation, si-RDX rescue/epistasis, migration/invasion assays, and nude-mouse xenograft","pmids":["29928443"],"confidence":"Medium","gaps":["Molecular pathway linking RDX to invasive behavior not defined","Single tumor type and cell line"]},{"year":2019,"claim":"Extended the DFNB24 mutational spectrum with new frameshift/nonsense variants, confirming the FERM-domain N-terminus is required for auditory function.","evidence":"NGS deafness-gene panel with Sanger segregation validation in a Chinese family","pmids":["31250571"],"confidence":"Medium","gaps":["Pathogenicity inferred from domain disruption rather than functional assay","No direct measurement of protein loss in patient tissue"]},{"year":2021,"claim":"Identified miR-196b-5p as a direct regulator of RDX in ovarian granulosa cells, linking RDX levels to proliferation, apoptosis, ROS, and steroidogenesis.","evidence":"Dual-luciferase target validation with RT-qPCR/Western and proliferation, apoptosis, and ROS readouts","pmids":["35071469"],"confidence":"Medium","gaps":["Mechanism connecting RDX to estrogen synthesis and glucose uptake not established","Single cell system"]},{"year":null,"claim":"Whether the CUL3-adaptor, Hedgehog-modulating, and PDK1-activating activities defined in Drosophila or in kinase-complex contexts are exercised by mammalian RDX, and how these reconcile with its stereocilia structural role, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct test of CUL3-adaptor or Hedgehog roles for human RDX","No unifying biochemical link between the cytoskeletal and ubiquitylation/signaling functions"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0,4]}],"complexes":["CUL3 E3 ubiquitin ligase (RDX/CAL1 adaptor module)"],"partners":["CAL1","CENP-A","SU(FU)","PDK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P35241","full_name":"Radixin","aliases":[],"length_aa":583,"mass_kda":68.6,"function":"Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane","subcellular_location":"Cell membrane; Cytoplasm, cytoskeleton; Cleavage furrow; Cell projection, microvillus; Cell projection, stereocilium","url":"https://www.uniprot.org/uniprotkb/P35241/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RDX","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"EZR","stoichiometry":0.2},{"gene":"MSN","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/RDX","total_profiled":1310},"omim":[{"mim_id":"618843","title":"LAYILIN; LAYN","url":"https://www.omim.org/entry/618843"},{"mim_id":"618003","title":"DEAFNESS, AUTOSOMAL RECESSIVE 57; DFNB57","url":"https://www.omim.org/entry/618003"},{"mim_id":"616042","title":"DEAFNESS, AUTOSOMAL RECESSIVE 103; DFNB103","url":"https://www.omim.org/entry/616042"},{"mim_id":"614555","title":"FERM DOMAIN-CONTAINING PROTEIN 6; FRMD6","url":"https://www.omim.org/entry/614555"},{"mim_id":"612971","title":"PDZ DOMAIN-CONTAINING 7; PDZD7","url":"https://www.omim.org/entry/612971"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"adrenal gland","ntpm":146.4}],"url":"https://www.proteinatlas.org/search/RDX"},"hgnc":{"alias_symbol":[],"prev_symbol":["DFNB24"]},"alphafold":{"accession":"P35241","domains":[{"cath_id":"3.10.20.90","chopping":"4-81","consensus_level":"high","plddt":95.5215,"start":4,"end":81},{"cath_id":"1.20.5","chopping":"303-356","consensus_level":"medium","plddt":92.683,"start":303,"end":356}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P35241","model_url":"https://alphafold.ebi.ac.uk/files/AF-P35241-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P35241-F1-predicted_aligned_error_v6.png","plddt_mean":86.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RDX","jax_strain_url":"https://www.jax.org/strain/search?query=RDX"},"sequence":{"accession":"P35241","fasta_url":"https://rest.uniprot.org/uniprotkb/P35241.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P35241/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P35241"}},"corpus_meta":[{"pmid":"7747953","id":"PMC_7747953","title":"Degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Stenotrophomonas maltophilia PB1.","date":"1995","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/7747953","citation_count":129,"is_preprint":false},{"pmid":"23725551","id":"PMC_23725551","title":"Role of black carbon electrical conductivity in mediating hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) transformation on carbon surfaces by sulfides.","date":"2013","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/23725551","citation_count":117,"is_preprint":false},{"pmid":"19270793","id":"PMC_19270793","title":"RDX induces aberrant expression of microRNAs in mouse brain and liver.","date":"2008","source":"Environmental health perspectives","url":"https://pubmed.ncbi.nlm.nih.gov/19270793","citation_count":108,"is_preprint":false},{"pmid":"16429147","id":"PMC_16429147","title":"An explosive-degrading cytochrome P450 activity and its targeted application for the phytoremediation of RDX.","date":"2006","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/16429147","citation_count":90,"is_preprint":false},{"pmid":"10749541","id":"PMC_10749541","title":"Type I nitroreductases in soil enterobacteria reduce TNT (2,4,6,-trinitrotoluene) and RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine).","date":"2000","source":"Canadian journal of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/10749541","citation_count":78,"is_preprint":false},{"pmid":"17058075","id":"PMC_17058075","title":"Biodegradation of the cyclic nitramine explosives RDX, HMX, and CL-20.","date":"2006","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/17058075","citation_count":71,"is_preprint":false},{"pmid":"12620815","id":"PMC_12620815","title":"Biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by a rabbit liver cytochrome P450: insight into the mechanism of RDX biodegradation by Rhodococcus sp. strain DN22.","date":"2003","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12620815","citation_count":69,"is_preprint":false},{"pmid":"17226784","id":"PMC_17226784","title":"Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus.","date":"2007","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/17226784","citation_count":66,"is_preprint":false},{"pmid":"25072885","id":"PMC_25072885","title":"Ag nanocluster/DNA hybrids: functional modules for the detection of nitroaromatic and RDX explosives.","date":"2014","source":"Nano letters","url":"https://pubmed.ncbi.nlm.nih.gov/25072885","citation_count":66,"is_preprint":false},{"pmid":"20704242","id":"PMC_20704242","title":"Black carbon-mediated destruction of nitroglycerin and RDX by hydrogen sulfide.","date":"2010","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/20704242","citation_count":65,"is_preprint":false},{"pmid":"18634047","id":"PMC_18634047","title":"Biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by a prospective consortium and its most effective isolate Serratia marcescens.","date":"1997","source":"Biotechnology and bioengineering","url":"https://pubmed.ncbi.nlm.nih.gov/18634047","citation_count":57,"is_preprint":false},{"pmid":"15060728","id":"PMC_15060728","title":"Anaerobic biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Acetobacterium malicum strain HAAP-1 isolated from a methanogenic mixed culture.","date":"2004","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/15060728","citation_count":56,"is_preprint":false},{"pmid":"19455327","id":"PMC_19455327","title":"Transformation of RDX and other energetic compounds by xenobiotic reductases XenA and XenB.","date":"2009","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/19455327","citation_count":51,"is_preprint":false},{"pmid":"34087636","id":"PMC_34087636","title":"Microbial community structure and metabolome profiling characteristics of soil contaminated by TNT, RDX, and HMX.","date":"2021","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/34087636","citation_count":42,"is_preprint":false},{"pmid":"16035760","id":"PMC_16035760","title":"Decomposition of nitramine energetic materials in excited electronic states: RDX and HMX.","date":"2005","source":"The Journal of chemical physics","url":"https://pubmed.ncbi.nlm.nih.gov/16035760","citation_count":39,"is_preprint":false},{"pmid":"17611801","id":"PMC_17611801","title":"Effect of organic and inorganic nitrogenous compounds on RDX degradation and cytochrome P-450 expression in Rhodococcus strain YH1.","date":"2007","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/17611801","citation_count":38,"is_preprint":false},{"pmid":"12174045","id":"PMC_12174045","title":"Evidence that RDX biodegradation by Rhodococcus strain DN22 is plasmid-borne and involves a cytochrome p-450.","date":"2002","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12174045","citation_count":36,"is_preprint":false},{"pmid":"24636256","id":"PMC_24636256","title":"The E3 ligase CUL3/RDX controls centromere maintenance by ubiquitylating and stabilizing CENP-A in a CAL1-dependent manner.","date":"2014","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/24636256","citation_count":36,"is_preprint":false},{"pmid":"12685743","id":"PMC_12685743","title":"Biodegradation pathways of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Clostridium acetobutylicum cell-free extract.","date":"2003","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/12685743","citation_count":35,"is_preprint":false},{"pmid":"19551222","id":"PMC_19551222","title":"Crystal structure prediction for cyclotrimethylene trinitramine (RDX) from first principles.","date":"2009","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/19551222","citation_count":34,"is_preprint":false},{"pmid":"21362589","id":"PMC_21362589","title":"RDX binds to the GABA(A) receptor-convulsant site and blocks GABA(A) receptor-mediated currents in the amygdala: a mechanism for RDX-induced seizures.","date":"2011","source":"Environmental health perspectives","url":"https://pubmed.ncbi.nlm.nih.gov/21362589","citation_count":33,"is_preprint":false},{"pmid":"18366604","id":"PMC_18366604","title":"Transcriptomic analysis of RDX and TNT interactive sublethal effects in the earthworm Eisenia fetida.","date":"2008","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18366604","citation_count":32,"is_preprint":false},{"pmid":"18239998","id":"PMC_18239998","title":"Biotransformation products and mineralization potential for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in abiotic versus biological degradation pathways with anthraquinone-2,6-disulfonate (AQDS) and Geobacter metallireducens.","date":"2008","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/18239998","citation_count":31,"is_preprint":false},{"pmid":"21327803","id":"PMC_21327803","title":"Isolation and characterization of RDX-degrading Rhodococcus species from a contaminated aquifer.","date":"2011","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/21327803","citation_count":30,"is_preprint":false},{"pmid":"19417177","id":"PMC_19417177","title":"Neurotoxicogenomic investigations to assess mechanisms of action of the munitions constituents RDX and 2,6-DNT in Northern bobwhite (Colinus virginianus).","date":"2009","source":"Toxicological sciences : an official journal of the Society of Toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/19417177","citation_count":30,"is_preprint":false},{"pmid":"34023765","id":"PMC_34023765","title":"Analysis of the biodegradation and phytotoxicity mechanism of TNT, RDX, HMX in alfalfa (Medicago sativa).","date":"2021","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/34023765","citation_count":29,"is_preprint":false},{"pmid":"15344514","id":"PMC_15344514","title":"The responses of selected terrestrial plants to short (<12 days) and long term (2, 4 and 6 weeks) hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) exposure. Part I: Growth and developmental effects.","date":"2004","source":"Ecotoxicology (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/15344514","citation_count":29,"is_preprint":false},{"pmid":"18774159","id":"PMC_18774159","title":"Metabolism of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in a contaminated vadose zone.","date":"2008","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/18774159","citation_count":28,"is_preprint":false},{"pmid":"17010461","id":"PMC_17010461","title":"A TaqMan polymerase chain reaction method for monitoring RDX-degrading bacteria based on the xplA functional gene.","date":"2006","source":"Journal of microbiological methods","url":"https://pubmed.ncbi.nlm.nih.gov/17010461","citation_count":27,"is_preprint":false},{"pmid":"21516383","id":"PMC_21516383","title":"Conserved toxic responses across divergent phylogenetic lineages: a meta-analysis of the neurotoxic effects of RDX among multiple species using toxicogenomics.","date":"2011","source":"Ecotoxicology (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21516383","citation_count":26,"is_preprint":false},{"pmid":"25559034","id":"PMC_25559034","title":"MicroRNA and messenger RNA profiling reveals new biomarkers and mechanisms for RDX induced neurotoxicity.","date":"2014","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/25559034","citation_count":24,"is_preprint":false},{"pmid":"18642890","id":"PMC_18642890","title":"Shock wave induced decomposition of RDX: quantum chemistry calculations.","date":"2008","source":"The journal of physical chemistry. A","url":"https://pubmed.ncbi.nlm.nih.gov/18642890","citation_count":24,"is_preprint":false},{"pmid":"23781876","id":"PMC_23781876","title":"Microbial community dynamics during acetate biostimulation of RDX-contaminated groundwater.","date":"2013","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/23781876","citation_count":24,"is_preprint":false},{"pmid":"18636641","id":"PMC_18636641","title":"Biological breakdown of RDX in slurry reactors proceeds with multiple kinetically distinguishable paths.","date":"1997","source":"Biotechnology and bioengineering","url":"https://pubmed.ncbi.nlm.nih.gov/18636641","citation_count":24,"is_preprint":false},{"pmid":"23603473","id":"PMC_23603473","title":"Application of (13)C-stable isotope probing to identify RDX-degrading microorganisms in groundwater.","date":"2013","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/23603473","citation_count":23,"is_preprint":false},{"pmid":"30488285","id":"PMC_30488285","title":"Genetic modification of western wheatgrass (Pascopyrum smithii) for the phytoremediation of RDX and TNT.","date":"2018","source":"Planta","url":"https://pubmed.ncbi.nlm.nih.gov/30488285","citation_count":21,"is_preprint":false},{"pmid":"21395947","id":"PMC_21395947","title":"Horizontal gene transfer (HGT) as a mechanism of disseminating RDX-degrading activity among Actinomycete bacteria.","date":"2011","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/21395947","citation_count":21,"is_preprint":false},{"pmid":"23275513","id":"PMC_23275513","title":"Role of nitrogen limitation in transformation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) by Gordonia sp. strain KTR9.","date":"2012","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23275513","citation_count":21,"is_preprint":false},{"pmid":"18459059","id":"PMC_18459059","title":"Cosubstrate independent mineralization of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by a Desulfovibrio species under anaerobic conditions.","date":"2008","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/18459059","citation_count":20,"is_preprint":false},{"pmid":"19926161","id":"PMC_19926161","title":"Quantifying RDX biodegradation in groundwater using delta15N isotope analysis.","date":"2009","source":"Journal of contaminant hydrology","url":"https://pubmed.ncbi.nlm.nih.gov/19926161","citation_count":20,"is_preprint":false},{"pmid":"35071469","id":"PMC_35071469","title":"Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17.","date":"2021","source":"Annals of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35071469","citation_count":19,"is_preprint":false},{"pmid":"29928443","id":"PMC_29928443","title":"miR-409-3p suppresses the proliferation, invasion and migration of tongue squamous cell carcinoma via targeting RDX.","date":"2018","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/29928443","citation_count":19,"is_preprint":false},{"pmid":"10852880","id":"PMC_10852880","title":"Genetic and phenotypic analyses of the rdx locus of Rhodobacter sphaeroides 2.4.1.","date":"2000","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/10852880","citation_count":18,"is_preprint":false},{"pmid":"23909596","id":"PMC_23909596","title":"Identification of microbial populations assimilating nitrogen from RDX in munitions contaminated military training range soils by high sensitivity stable isotope probing.","date":"2013","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/23909596","citation_count":18,"is_preprint":false},{"pmid":"25935409","id":"PMC_25935409","title":"Application of (13)C and (15)N stable isotope probing to characterize RDX degrading microbial communities under different electron-accepting conditions.","date":"2015","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/25935409","citation_count":18,"is_preprint":false},{"pmid":"22697906","id":"PMC_22697906","title":"A systems toxicology approach to elucidate the mechanisms involved in RDX species-specific sensitivity.","date":"2012","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/22697906","citation_count":17,"is_preprint":false},{"pmid":"20965580","id":"PMC_20965580","title":"Investigations of transcript expression in fathead minnow (Pimephales promelas) brain tissue reveal toxicological impacts of RDX exposure.","date":"2010","source":"Aquatic toxicology (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/20965580","citation_count":17,"is_preprint":false},{"pmid":"21105645","id":"PMC_21105645","title":"Biodegradation of RDX and MNX with Rhodococcus sp. strain DN22: new insights into the degradation pathway.","date":"2010","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/21105645","citation_count":16,"is_preprint":false},{"pmid":"25661171","id":"PMC_25661171","title":"Improved RDX detoxification with starch addition using a novel nitrogen-fixing aerobic microbial consortium from soil contaminated with explosives.","date":"2015","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/25661171","citation_count":16,"is_preprint":false},{"pmid":"15309341","id":"PMC_15309341","title":"Characterization of Pseudomonas sp. HK-6 cells responding to explosive RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine).","date":"2004","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/15309341","citation_count":16,"is_preprint":false},{"pmid":"22688904","id":"PMC_22688904","title":"Anaerobic bioremediation of RDX by ovine whole rumen fluid and pure culture isolates.","date":"2012","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/22688904","citation_count":15,"is_preprint":false},{"pmid":"12413787","id":"PMC_12413787","title":"The use of Enterobacter cloacae ATCC 43560 in the development of a two-phase partitioning bioreactor for the destruction of hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX).","date":"2003","source":"Journal of biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/12413787","citation_count":15,"is_preprint":false},{"pmid":"26637031","id":"PMC_26637031","title":"Reaction Mechanism of 1,3,5-Trinitro-s-triazine (RDX) Deciphered by Density Functional Theory.","date":"2007","source":"Journal of chemical theory and computation","url":"https://pubmed.ncbi.nlm.nih.gov/26637031","citation_count":15,"is_preprint":false},{"pmid":"17125323","id":"PMC_17125323","title":"Crystal structure of the high-pressure phase of hexahydro-1,3,5-trinitro-1,3,5-triazine (gamma-RDX).","date":"2006","source":"The journal of physical chemistry. B","url":"https://pubmed.ncbi.nlm.nih.gov/17125323","citation_count":15,"is_preprint":false},{"pmid":"28432960","id":"PMC_28432960","title":"Molecular dynamic simulations on TKX-50/RDX cocrystal.","date":"2017","source":"Journal of molecular graphics & modelling","url":"https://pubmed.ncbi.nlm.nih.gov/28432960","citation_count":14,"is_preprint":false},{"pmid":"25383623","id":"PMC_25383623","title":"Metagenomic insights into the RDX-degrading potential of the ovine rumen microbiome.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25383623","citation_count":14,"is_preprint":false},{"pmid":"27118012","id":"PMC_27118012","title":"Microbial community characterization and functional gene quantification in RDX-degrading microcosms derived from sediment and groundwater at two naval sites.","date":"2016","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/27118012","citation_count":14,"is_preprint":false},{"pmid":"31250571","id":"PMC_31250571","title":"Identification of novel variants in MYO15A, OTOF, and RDX with hearing loss by next-generation sequencing.","date":"2019","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31250571","citation_count":14,"is_preprint":false},{"pmid":"26438043","id":"PMC_26438043","title":"Evaluation of microbial transport during aerobic bioaugmentation of an RDX-contaminated aquifer.","date":"2015","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/26438043","citation_count":14,"is_preprint":false},{"pmid":"22873636","id":"PMC_22873636","title":"Decomposition of γ-cyclotrimethylene trinitramine (γ-RDX): relevance for shock wave initiation.","date":"2012","source":"The journal of physical chemistry. A","url":"https://pubmed.ncbi.nlm.nih.gov/22873636","citation_count":14,"is_preprint":false},{"pmid":"36259743","id":"PMC_36259743","title":"Revealing the thermal decomposition mechanism of RDX crystals by a neural network potential.","date":"2022","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/36259743","citation_count":13,"is_preprint":false},{"pmid":"27016566","id":"PMC_27016566","title":"Relating Carbon and Nitrogen Isotope Effects to Reaction Mechanisms during Aerobic or Anaerobic Degradation of RDX (Hexahydro-1,3,5-Trinitro-1,3,5-Triazine) by Pure Bacterial Cultures.","date":"2016","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27016566","citation_count":13,"is_preprint":false},{"pmid":"35077733","id":"PMC_35077733","title":"A sketch of microbiological remediation of explosives-contaminated soil focused on state of art and the impact of technological advancement on hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation.","date":"2022","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/35077733","citation_count":12,"is_preprint":false},{"pmid":"21340737","id":"PMC_21340737","title":"Ovine ruminal microbes are capable of biotransforming hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).","date":"2011","source":"Microbial ecology","url":"https://pubmed.ncbi.nlm.nih.gov/21340737","citation_count":12,"is_preprint":false},{"pmid":"25594316","id":"PMC_25594316","title":"Mineralization of RDX-derived nitrogen to N2 via denitrification in coastal marine sediments.","date":"2015","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/25594316","citation_count":12,"is_preprint":false},{"pmid":"21538488","id":"PMC_21538488","title":"Genomic investigation of year-long and multigenerational exposures of fathead minnow to the munitions compound RDX.","date":"2011","source":"Environmental toxicology and chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21538488","citation_count":12,"is_preprint":false},{"pmid":"21452829","id":"PMC_21452829","title":"Transformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by permanganate.","date":"2011","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/21452829","citation_count":12,"is_preprint":false},{"pmid":"25503243","id":"PMC_25503243","title":"Laboratory evaluation of bioaugmentation for aerobic treatment of RDX in groundwater.","date":"2014","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/25503243","citation_count":12,"is_preprint":false},{"pmid":"31347632","id":"PMC_31347632","title":"The solid phase thermal decomposition and nanocrystal effect of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) via ReaxFF large-scale molecular dynamics simulation.","date":"2019","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/31347632","citation_count":12,"is_preprint":false},{"pmid":"25742010","id":"PMC_25742010","title":"PKCη/Rdx-driven phosphorylation of PDK1: a novel mechanism promoting cancer cell survival and permissiveness for parvovirus-induced lysis.","date":"2015","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/25742010","citation_count":11,"is_preprint":false},{"pmid":"25142696","id":"PMC_25142696","title":"The essential role of nitrogen limitation in expression of xplA and degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in Gordonia sp. strain KTR9.","date":"2014","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/25142696","citation_count":11,"is_preprint":false},{"pmid":"24687782","id":"PMC_24687782","title":"Physiological and transcriptional responses of Baccharis halimifolia to the explosive \"composition B\" (RDX/TNT) in amended soil.","date":"2014","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/24687782","citation_count":11,"is_preprint":false},{"pmid":"25721530","id":"PMC_25721530","title":"Stable isotope probing reveals the importance of Comamonas and Pseudomonadaceae in RDX degradation in samples from a Navy detonation site.","date":"2015","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/25721530","citation_count":11,"is_preprint":false},{"pmid":"28900455","id":"PMC_28900455","title":"Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran.","date":"2017","source":"Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/28900455","citation_count":10,"is_preprint":false},{"pmid":"34998745","id":"PMC_34998745","title":"Reshaping the microenvironment and bacterial community of TNT- and RDX-contaminated soil by combined remediation with vetiver grass (Vetiveria ziznioides) and effective microorganism (EM) flora.","date":"2022","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/34998745","citation_count":10,"is_preprint":false},{"pmid":"27387802","id":"PMC_27387802","title":"Identification of groundwater microorganisms capable of assimilating RDX-derived nitrogen during in-situ bioremediation.","date":"2016","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/27387802","citation_count":10,"is_preprint":false},{"pmid":"17360228","id":"PMC_17360228","title":"Examination of the mutagenicity of RDX and its N-nitroso metabolites using the Salmonella reverse mutation assay.","date":"2007","source":"Mutation research","url":"https://pubmed.ncbi.nlm.nih.gov/17360228","citation_count":10,"is_preprint":false},{"pmid":"31911385","id":"PMC_31911385","title":"Spatially-distinct redox conditions and degradation rates following field-scale bioaugmentation for RDX-contaminated groundwater remediation.","date":"2019","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/31911385","citation_count":10,"is_preprint":false},{"pmid":"22260206","id":"PMC_22260206","title":"Involvement of cytochrome c CymA in the anaerobic metabolism of RDX by Shewanella oneidensis MR-1.","date":"2012","source":"Canadian journal of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22260206","citation_count":10,"is_preprint":false},{"pmid":"16393935","id":"PMC_16393935","title":"Genotoxicity assessment of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).","date":"2005","source":"International journal of toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/16393935","citation_count":10,"is_preprint":false},{"pmid":"32659577","id":"PMC_32659577","title":"A novel egg shell-based bio formulation for remediation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) contaminated soil.","date":"2020","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/32659577","citation_count":10,"is_preprint":false},{"pmid":"38477375","id":"PMC_38477375","title":"Determining the mechanical and decomposition properties of high energetic materials (α-RDX, β-HMX, and ε-CL-20) using a neural network potential.","date":"2024","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/38477375","citation_count":9,"is_preprint":false},{"pmid":"34051563","id":"PMC_34051563","title":"In-vessel composting of HMX and RDX contaminated sludge using microbes isolated from contaminated site.","date":"2021","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/34051563","citation_count":9,"is_preprint":false},{"pmid":"36002099","id":"PMC_36002099","title":"Inhibition effect of 2,4,6-trinitrotoluene (TNT) on RDX degradation by rhodococcus strains isolated from contaminated soil and water.","date":"2022","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/36002099","citation_count":9,"is_preprint":false},{"pmid":"28417168","id":"PMC_28417168","title":"RDX degradation in bioaugmented model aquifer columns under aerobic and low oxygen conditions.","date":"2017","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/28417168","citation_count":9,"is_preprint":false},{"pmid":"32109698","id":"PMC_32109698","title":"Application of a multiple lines of evidence approach to document natural attenuation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in groundwater.","date":"2020","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/32109698","citation_count":9,"is_preprint":false},{"pmid":"25913213","id":"PMC_25913213","title":"A comparative study of microbial communities in four soil slurries capable of RDX degradation using illumina sequencing.","date":"2015","source":"Biodegradation","url":"https://pubmed.ncbi.nlm.nih.gov/25913213","citation_count":9,"is_preprint":false},{"pmid":"31783711","id":"PMC_31783711","title":"Improving the Chemical Selectivity of an Electronic Nose to TNT, DNT and RDX Using Machine Learning.","date":"2019","source":"Sensors (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31783711","citation_count":9,"is_preprint":false},{"pmid":"16802206","id":"PMC_16802206","title":"Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) serves as a carbon and energy source for a mixed culture under anaerobic conditions.","date":"2006","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16802206","citation_count":9,"is_preprint":false},{"pmid":"34357428","id":"PMC_34357428","title":"Diversity and abundance of the functional genes and bacteria associated with RDX degradation at a contaminated site pre- and post-biostimulation.","date":"2021","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/34357428","citation_count":8,"is_preprint":false},{"pmid":"15030142","id":"PMC_15030142","title":"Biodegradation of 1,3,5-trinitro-1,3,5-triazine (RDX).","date":"2004","source":"Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering","url":"https://pubmed.ncbi.nlm.nih.gov/15030142","citation_count":8,"is_preprint":false},{"pmid":"28004139","id":"PMC_28004139","title":"Genome Shuffling of Stenotrophomonas maltophilia OK-5 for Improving the Degradation of Explosive RDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine).","date":"2016","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28004139","citation_count":8,"is_preprint":false},{"pmid":"35539229","id":"PMC_35539229","title":"Shock response of condensed-phase RDX: molecular dynamics simulations in conjunction with the MSST method.","date":"2018","source":"RSC advances","url":"https://pubmed.ncbi.nlm.nih.gov/35539229","citation_count":8,"is_preprint":false},{"pmid":"37257349","id":"PMC_37257349","title":"Multi-generation reproductive toxicity of RDX and the involved signal pathways in Caenorhabditis elegans.","date":"2023","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/37257349","citation_count":7,"is_preprint":false},{"pmid":"24522483","id":"PMC_24522483","title":"Clostridium geopurificans strain MJ1 sp. nov., a strictly anaerobic bacterium that grows via fermentation and reduces the cyclic nitramine explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).","date":"2014","source":"Current microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/24522483","citation_count":7,"is_preprint":false},{"pmid":"31048167","id":"PMC_31048167","title":"Manipulating redox conditions to enhance in situ bioremediation of RDX in groundwater at a contaminated site.","date":"2019","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/31048167","citation_count":7,"is_preprint":false},{"pmid":"35324073","id":"PMC_35324073","title":"The seizure-inducing plastic explosive RDX inhibits the α1β2γ2 GABAA receptor.","date":"2022","source":"Annals of clinical and translational neurology","url":"https://pubmed.ncbi.nlm.nih.gov/35324073","citation_count":6,"is_preprint":false},{"pmid":"31352507","id":"PMC_31352507","title":"High throughput quantification of the functional genes associated with RDX biodegradation using the SmartChip real-time PCR system.","date":"2019","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/31352507","citation_count":6,"is_preprint":false},{"pmid":"35336238","id":"PMC_35336238","title":"Effects of Perchlorate and Other Groundwater Inorganic Co-Contaminants on Aerobic RDX Degradation.","date":"2022","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/35336238","citation_count":5,"is_preprint":false},{"pmid":"23216924","id":"PMC_23216924","title":"Su(fu) switches Rdx functions to fine-tune hedgehog signaling in the Drosophila wing disk.","date":"2012","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/23216924","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":51485,"output_tokens":2665,"usd":0.097215,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9422,"output_tokens":2670,"usd":0.05693,"stage2_stop_reason":"end_turn"},"total_usd":0.154145,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the human/mammalian gene RDX (radixin, DFNB24) vs. papers about the explosive compound RDX or other unrelated uses of the symbol.\n\n**Canonical gene papers:** \n- PMID 17226784: RDX gene mutations → radixin → DFNB24 hearing loss\n- PMID 24636256: CUL3/RDX E3 ligase in Drosophila (Rdx/HIB adaptor)\n- PMID 25742010: PKCη/Rdx phosphorylates PDK1\n- PMID 35071469: miR-196b-5p targets RDX (radixin) in granulosa cells\n- PMID 29928443: miR-409-3p targets RDX in TSCC\n- PMID 23216924: Drosophila Rdx (Roadkill/HIB) in Hh signaling\n- PMID 31250571: RDX gene variants in hearing loss (next-gen sequencing)\n- PMID 28900455: DFNB24 locus linkage study — no linkage found (negative result)\n\nAll others are about the explosive compound or unrelated symbols.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"Loss-of-function mutations in RDX (radixin) — including p.D578N affecting the actin-binding motif, p.A469fsX487 (frameshift), and p.Q155X truncating the FERM domain — segregate with autosomal recessive nonsyndromic sensorineural hearing loss (DFNB24) in consanguineous Pakistani families. High-resolution confocal microscopy in mouse inner ear demonstrated that radixin is expressed along the length of stereocilia of hair cells in the organ of Corti and vestibular system, establishing a direct role in stereocilia maintenance.\",\n      \"method\": \"Sanger sequencing of consanguineous families, domain-level mutation analysis predicting disruption of actin-binding motif and FERM domain, high-resolution confocal microscopy of mouse inner ear\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple independent disease-segregating mutations with domain-level mechanistic interpretation, replicated across two families plus original DFNB24 family, with direct localization by confocal microscopy in hair cells\",\n      \"pmids\": [\"17226784\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Drosophila, the CUL3 adaptor RDX (Roadkill/HIB) directly interacts with the CENP-A loading factor CAL1. CAL1 is not itself a substrate but acts as an additional substrate-specifying factor for CUL3/RDX-mediated ubiquitylation of CENP-A. Crucially, CUL3/RDX-mediated ubiquitylation stabilizes rather than degrades CENP-A and CAL1; loss of RDX causes rapid degradation of both proteins and massive chromosome segregation defects.\",\n      \"method\": \"Co-immunoprecipitation, in vivo ubiquitylation assays, RNAi/genetic loss-of-function in Drosophila, immunofluorescence, epistasis analysis\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vivo ubiquitylation, genetic KD with clear cellular phenotype (chromosome segregation defects), multiple orthogonal methods in one study\",\n      \"pmids\": [\"24636256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PKCη/Rdx (a parvovirus-induced kinase complex) phosphorylates mouse PDK1 at Ser138 (corresponding to human PDK1-pSer135), activating PDK1 independently of PI3-kinase signaling. This represents a novel intracellular loop-back mechanism whereby parvovirus-activated PKCη uses Rdx to sustain PDK1 activity and cancer cell survival.\",\n      \"method\": \"In vitro kinase assay, phospho-specific antibody detection, expression of constitutively active PDK1 mutant mimicking the phosphorylation, cell-based viral DNA amplification assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro kinase assay plus cell-based functional rescue with constitutively active PDK1 mimetic, single lab but two orthogonal approaches\",\n      \"pmids\": [\"25742010\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In Drosophila wing discs, Suppressor of fused (Su(fu)) controls a switch in Rdx (Roadkill) mechanism: in the absence of Su(fu) (strong Hh signal), Rdx blocks nuclear entry of Ci-155; in the presence of Su(fu) (moderate Hh), Rdx induces nuclear degradation of Ci-155. Strong Hh induces rdx and suppresses su(fu) expression; moderate Hh induces moderate rdx and high su(fu). This dual-mode action of Rdx fine-tunes Hh signaling output.\",\n      \"method\": \"Genetic epistasis in Drosophila wing discs, immunofluorescence for Ci-155 localization, in vivo expression analysis, loss-of-function and overexpression of rdx and su(fu)\",\n      \"journal\": \"Genes to cells : devoted to molecular & cellular mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with multiple allele combinations and direct protein localization readout, single lab\",\n      \"pmids\": [\"23216924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Novel compound heterozygous variants in RDX (c.129_130del, p.His43Glnfs*28 and c.76_79del, p.Lys26*) were identified in a Chinese family with autosomal recessive nonsyndromic hearing loss, extending the mutational spectrum of DFNB24 and confirming the essential role of the radixin FERM domain N-terminus in auditory function.\",\n      \"method\": \"Next-generation sequencing of 227 known deafness genes, Sanger sequencing validation in family members\",\n      \"journal\": \"Molecular genetics & genomic medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — NGS with Sanger validation in a family, segregation confirmed, but mechanistic inference is by domain disruption prediction rather than direct functional assay\",\n      \"pmids\": [\"31250571\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"miR-196b-5p directly targets RDX (radixin) mRNA, as confirmed by dual-luciferase reporter assay. Downregulation of miR-196b-5p increased RDX protein levels in ovarian granulosa cells, promoted apoptosis, inhibited proliferation, increased ROS production, and reduced estrogen synthesis (CYP19A1) and glucose uptake (GLUT4). Transfection with miR-196b-5p mimics reduced RDX levels and reversed these effects.\",\n      \"method\": \"Dual-luciferase reporter assay (direct target validation), RT-qPCR, Western blot, CCK8 proliferation assay, flow cytometry for apoptosis and ROS\",\n      \"journal\": \"Annals of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct miRNA-target validation by luciferase assay plus multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"35071469\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"miR-409-3p directly targets RDX (radixin) mRNA in tongue squamous cell carcinoma (TSCC), validated by dual-luciferase reporter assay. miR-409-3p mimic reduced RDX expression and suppressed proliferation, migration, and invasion of Tca8113 cells; miR-409-3p inhibitor increased RDX and enhanced these activities. si-RDX phenocopied miR-409-3p mimic and reversed the inhibitor effect, placing RDX downstream of miR-409-3p in regulating TSCC cell behavior. Tumor xenograft experiments confirmed that miR-409-3p mimic inhibited tumor growth and lymph node metastasis.\",\n      \"method\": \"Dual-luciferase reporter assay, RT-qPCR, Western blot, CCK-8, wound-healing, Transwell invasion assays, si-RNA knockdown, nude mouse xenograft\",\n      \"journal\": \"Oncology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct target validation by luciferase plus multiple orthogonal cellular/in vivo assays, genetic epistasis via si-RDX rescue, single lab\",\n      \"pmids\": [\"29928443\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Radixin (RDX/DFNB24) is an ERM-family protein that cross-links membrane proteins to the actin cytoskeleton via its FERM domain and C-terminal actin-binding motif; loss-of-function mutations in either domain cause autosomal recessive sensorineural hearing loss (DFNB24) through degeneration of inner ear hair cell stereocilia. In Drosophila, the orthologous Rdx/Roadkill serves as a CUL3 E3 ubiquitin ligase adaptor that stabilizes (rather than degrades) the centromeric histone CENP-A in a CAL1-dependent manner and, in the Hedgehog pathway, switches between blocking Ci-155 nuclear entry and promoting its nuclear degradation depending on Su(fu) levels. Additionally, PKCη/Rdx has been shown to directly phosphorylate PDK1-Ser138, activating it independently of PI3K, and RDX protein levels are post-translationally regulated by miR-196b-5p and miR-409-3p in granulosa cells and tongue squamous carcinoma cells, respectively.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RDX (radixin) is an actin-cytoskeleton-linking ERM-family protein whose integrity is essential for sensory hair cell function: loss-of-function mutations disrupting either its FERM domain or its C-terminal actin-binding motif segregate with autosomal recessive nonsyndromic sensorineural hearing loss (DFNB24), and radixin localizes along the length of hair cell stereocilia in the organ of Corti and vestibular system, indicating a direct structural role in stereocilia maintenance [#0, #4]. Studies of the Drosophila ortholog (Roadkill/HIB) reveal an independent function as a CUL3 E3 ubiquitin ligase substrate-specifying adaptor: in complex with CAL1 it ubiquitylates the centromeric histone CENP-A in a manner that stabilizes rather than degrades it, so that RDX loss triggers CENP-A/CAL1 degradation and chromosome segregation defects [#1], and within Hedgehog signaling it acts in a Su(fu)-dependent dual mode, either blocking nuclear entry of Ci-155 or promoting its nuclear degradation to tune pathway output [#3]. RDX has also been placed in a parvovirus-induced PKCη/Rdx kinase complex that phosphorylates PDK1 at Ser138 to activate it independently of PI3-kinase [#2], and its protein abundance is post-transcriptionally controlled by direct miRNA targeting (miR-196b-5p in ovarian granulosa cells, miR-409-3p in tongue squamous carcinoma), where reducing RDX alters proliferation, apoptosis, migration, and invasion [#5, #6].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established that RDX is a human deafness gene and tied its function to stereocilia, answering whether radixin has a non-redundant physiological role in the inner ear.\",\n      \"evidence\": \"Sanger sequencing of consanguineous families identifying FERM-domain and actin-binding-motif mutations, with confocal localization in mouse inner ear\",\n      \"pmids\": [\"17226784\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which radixin loss leads to stereocilia degeneration not resolved at the molecular level\", \"No direct biochemical assay of the disease mutations' effect on membrane-actin cross-linking\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved how the Drosophila ortholog can produce opposite effects on Hedgehog signaling, showing Su(fu) levels switch Rdx between blocking Ci-155 nuclear entry and promoting its nuclear degradation.\",\n      \"evidence\": \"Genetic epistasis and Ci-155 immunofluorescence localization in Drosophila wing discs with rdx/su(fu) loss- and gain-of-function\",\n      \"pmids\": [\"23216924\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Conducted in Drosophila; relevance to mammalian RDX not addressed\", \"Biochemical basis of the Su(fu)-dependent switch not defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined a CUL3-adaptor role for the ortholog in which ubiquitylation stabilizes rather than degrades its target, explaining how RDX maintains centromeric CENP-A.\",\n      \"evidence\": \"Reciprocal Co-IP, in vivo ubiquitylation assays, and RNAi/genetic loss-of-function with chromosome-segregation phenotyping in Drosophila\",\n      \"pmids\": [\"24636256\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Demonstrated in Drosophila; whether human RDX functions as a CUL3 adaptor is untested\", \"Molecular basis for non-degradative ubiquitylation not defined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Implicated an Rdx-containing kinase complex in direct activation of PDK1, identifying a PI3K-independent route to PDK1 activity.\",\n      \"evidence\": \"In vitro kinase assay with phospho-specific detection plus cell-based rescue using a constitutively active PDK1 phosphomimetic\",\n      \"pmids\": [\"25742010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; reciprocal validation and structural basis lacking\", \"Direct kinase role attributed to PKCη/Rdx complex rather than RDX alone\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed RDX abundance is directly controlled by miR-409-3p and that RDX acts downstream to drive tumor cell proliferation, migration, and invasion in tongue squamous carcinoma.\",\n      \"evidence\": \"Dual-luciferase target validation, si-RDX rescue/epistasis, migration/invasion assays, and nude-mouse xenograft\",\n      \"pmids\": [\"29928443\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway linking RDX to invasive behavior not defined\", \"Single tumor type and cell line\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended the DFNB24 mutational spectrum with new frameshift/nonsense variants, confirming the FERM-domain N-terminus is required for auditory function.\",\n      \"evidence\": \"NGS deafness-gene panel with Sanger segregation validation in a Chinese family\",\n      \"pmids\": [\"31250571\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Pathogenicity inferred from domain disruption rather than functional assay\", \"No direct measurement of protein loss in patient tissue\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified miR-196b-5p as a direct regulator of RDX in ovarian granulosa cells, linking RDX levels to proliferation, apoptosis, ROS, and steroidogenesis.\",\n      \"evidence\": \"Dual-luciferase target validation with RT-qPCR/Western and proliferation, apoptosis, and ROS readouts\",\n      \"pmids\": [\"35071469\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting RDX to estrogen synthesis and glucose uptake not established\", \"Single cell system\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the CUL3-adaptor, Hedgehog-modulating, and PDK1-activating activities defined in Drosophila or in kinase-complex contexts are exercised by mammalian RDX, and how these reconcile with its stereocilia structural role, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct test of CUL3-adaptor or Hedgehog roles for human RDX\", \"No unifying biochemical link between the cytoskeletal and ubiquitylation/signaling functions\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"complexes\": [\"CUL3 E3 ubiquitin ligase (RDX/CAL1 adaptor module)\"],\n    \"partners\": [\"CAL1\", \"CENP-A\", \"Su(fu)\", \"PDK1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}