{"gene":"PRX","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2018,"finding":"Periaxin (PRX) is expressed in human cerebral endothelial cells (but not in brain endothelium of other mammalian species), where it localizes predominantly to the nucleus. Overexpression of PRX in mouse endothelial cells strengthens barrier function, significantly increases transendothelial electrical resistance (~35%), and reduces permeability of a wide range of molecules. The PDZ domain of PRX is necessary and sufficient for these barrier-enhancing properties, as a splice variant (S-PRX) containing only the PDZ domain also increases barrier function. PRX expression also suppresses a panel of inflammatory markers (predominantly Type I interferon response genes) by at least 50%.","method":"Transcriptome analysis, transendothelial electrical resistance measurement, permeability assays, overexpression of full-length PRX and PDZ-only splice variant (S-PRX) in mouse endothelial cells, immunofluorescence localization","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal functional assays (TER, permeability, transcriptomics, domain dissection) in a single lab; no independent replication","pmids":["29968755"],"is_preprint":false},{"year":2025,"finding":"Splicing defects in the final intron of PRX (intron 6 of PRXb/L-PRX) cause dominant congenital cataract. Variants within the splice region cause aberrant splicing confirmed by RNA sequencing, including intron 6 retention (switching expression to the S-PRX isoform) and/or use of alternate donor/acceptor sites yielding small in-frame deletions in L-PRX. Loss-of-function variants affecting L-PRX (or both isoforms) cause recessive neurological phenotypes without cataract, whereas dominant cataract results specifically from disruption of L-PRX splicing, possibly through a gain-of-function or dominant-negative mechanism. PRX is thus necessary for proper organization of the lens cortex adherens junction.","method":"Exome and genome sequencing, RNA sequencing to confirm aberrant splicing in affected individuals from four families, isoform analysis","journal":"Investigative ophthalmology & visual science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA-seq confirmation of aberrant splicing in multiple families with orthogonal sequencing methods; single study, no functional reconstitution","pmids":["41230902"],"is_preprint":false},{"year":2006,"finding":"A novel frameshift mutation (S399fsX410) in the PRX gene produces a truncated periaxin protein lacking the C-terminal domain, causing early-onset Charcot-Marie-Tooth type 4F (CMT4F) demyelinating neuropathy. This establishes that the C-terminal region of periaxin is required for normal peripheral nerve myelin maintenance.","method":"Genetic sequencing of PRX gene in CMT4F patient, protein-level analysis of truncation effect","journal":"Neurology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single patient genetic identification with protein-level characterization; no functional reconstitution or mechanistic dissection beyond mutation identification","pmids":["16534116"],"is_preprint":false},{"year":2011,"finding":"Novel homozygous nonsense mutation in PRX (c.1090C>T, p.Arg364X) causes CMT4F with a late-onset and relatively benign clinical course, broadening the genotype-phenotype spectrum. PRX mutations cause severe demyelination of peripheral nerves with focally folded myelin on nerve biopsy, establishing PRX as required for normal myelin architecture.","method":"Genetic sequencing, nerve biopsy histopathology","journal":"Neuromuscular disorders : NMD","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic identification with histopathological phenotype; no molecular mechanistic experiment","pmids":["21741241"],"is_preprint":false},{"year":2008,"finding":"A novel homozygous PRX mutation (A700PfsX17) causes early-onset demyelinating autosomal recessive CMT with severe sensory loss and sensory ataxia, establishing that PRX function is required for sensory as well as motor peripheral nerve myelin maintenance.","method":"Genetic sequencing of PRX gene in a consanguineous family with early-onset CMT","journal":"Neuropediatrics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic identification; no molecular mechanistic experiment beyond mutation-phenotype linkage","pmids":["18504680"],"is_preprint":false},{"year":2014,"finding":"Compound heterozygous nonsense mutations in PRX (p.R392X and p.R679X) cause Dejerine-Sottas neuropathy (DSN) with early-onset slowly progressive demyelinating neuropathy and prominent sensory involvement, demonstrating that biallelic loss-of-function of periaxin is sufficient to cause severe demyelinating peripheral neuropathy.","method":"Whole-exome sequencing, capillary sequencing, co-segregation analysis","journal":"Journal of clinical neurology (Seoul, Korea)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic identification with clinical phenotyping; no biochemical or cell biological mechanistic experiment","pmids":["25628743"],"is_preprint":false}],"current_model":"Periaxin (PRX), a PDZ-domain-containing protein encoded by the PRX/KIAA1620 gene, is required for maintenance of peripheral nerve myelin (loss-of-function mutations cause autosomal recessive CMT4F/Dejerine-Sottas demyelinating neuropathy); in human cerebral endothelial cells PRX localizes predominantly to the nucleus and its PDZ domain is necessary and sufficient to strengthen endothelial barrier function and suppress interferon-response inflammatory gene expression; isoform-specific splicing defects that replace L-PRX with S-PRX disrupt lens cortex adherens junction organization and cause dominant congenital cataract through a mechanism distinct from the recessive neurological phenotype."},"narrative":{"mechanistic_narrative":"Periaxin (PRX) is a PDZ-domain-containing protein required for the maintenance of peripheral nerve myelin, where biallelic loss-of-function mutations cause early-onset demyelinating Charcot-Marie-Tooth type 4F and Dejerine-Sottas neuropathy with prominent sensory and motor involvement and focally folded myelin on nerve biopsy [PMID:21741241, PMID:25628743]. Truncations that remove the C-terminal region of the long isoform (L-PRX) abolish normal myelin architecture, establishing that this domain is essential for peripheral nerve function [PMID:16534116, PMID:18504680]. The PRX locus produces distinct isoforms with separable functions: in human cerebral endothelial cells PRX localizes predominantly to the nucleus, where its PDZ domain is necessary and sufficient to strengthen endothelial barrier integrity and suppress Type I interferon-response inflammatory genes [PMID:29968755]. Isoform-specific splicing defects in the final intron of L-PRX—causing intron retention that switches expression to the PDZ-only S-PRX isoform or small in-frame deletions—disrupt lens cortex adherens junction organization and cause dominant congenital cataract through a mechanism distinct from the recessive neurological phenotype [PMID:41230902]. Beyond these genetic and barrier-function findings, the molecular partners and biochemical activity of periaxin have not been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Established that the C-terminal region of periaxin is required for peripheral nerve myelin maintenance by linking a frameshift truncation to demyelinating neuropathy.","evidence":"Genetic sequencing and protein-level truncation analysis in a CMT4F patient","pmids":["16534116"],"confidence":"Low","gaps":["Single patient without functional reconstitution","No mechanistic dissection of how C-terminal loss disrupts myelin","Molecular partners of the C-terminal domain unidentified"]},{"year":2008,"claim":"Extended periaxin's required role to sensory as well as motor peripheral nerve myelin, showing the deficit is not motor-restricted.","evidence":"Genetic sequencing of a homozygous frameshift variant in a consanguineous early-onset CMT family","pmids":["18504680"],"confidence":"Low","gaps":["Genotype-phenotype linkage only, no molecular experiment","Mechanism of sensory fiber vulnerability unknown"]},{"year":2011,"claim":"Broadened the clinical spectrum of PRX loss to late-onset benign neuropathy and tied PRX deficiency to focally folded myelin architecture on biopsy.","evidence":"Genetic sequencing and nerve biopsy histopathology of a homozygous nonsense variant","pmids":["21741241"],"confidence":"Low","gaps":["No molecular mechanistic experiment","Basis for variable onset/severity unexplained"]},{"year":2014,"claim":"Demonstrated that biallelic loss-of-function of periaxin is sufficient to cause severe Dejerine-Sottas demyelinating neuropathy, consolidating the recessive loss-of-function model.","evidence":"Whole-exome and capillary sequencing with co-segregation analysis of compound heterozygous nonsense variants","pmids":["25628743"],"confidence":"Low","gaps":["No biochemical or cell-biological mechanism","Downstream effectors in Schwann cell myelination unidentified"]},{"year":2018,"claim":"Revealed a non-neural function for PRX: nuclear localization in human cerebral endothelial cells where its PDZ domain enhances barrier integrity and suppresses interferon-response inflammation.","evidence":"Transcriptomics, transendothelial resistance and permeability assays, and PDZ-only (S-PRX) domain dissection by overexpression in mouse endothelial cells","pmids":["29968755"],"confidence":"Medium","gaps":["Single lab, no independent replication","Nuclear mechanism by which a PDZ domain strengthens barrier function unresolved","Direct interaction partners and target transcription circuit unidentified"]},{"year":2025,"claim":"Distinguished isoform-specific pathology: disruption of L-PRX splicing (intron retention favoring S-PRX or in-frame deletions) causes dominant congenital cataract via lens adherens junction disorganization, mechanistically separate from recessive neuropathy.","evidence":"Exome/genome and RNA sequencing confirming aberrant splicing across four cataract families","pmids":["41230902"],"confidence":"Medium","gaps":["No functional reconstitution of the dominant-negative/gain-of-function mechanism","Molecular basis of L-PRX's role at lens adherens junctions undefined","Single study"]},{"year":null,"claim":"The direct molecular partners, biochemical activity, and the structural basis by which the PDZ and C-terminal domains organize junctions and myelin remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identified direct physical interactors","No structural model linking domain function to junction or myelin organization","Mechanism reconciling nuclear endothelial role with junctional/myelin roles unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BXM0","full_name":"Periaxin","aliases":[],"length_aa":1461,"mass_kda":154.9,"function":"Scaffolding protein that functions as part of a dystroglycan complex in Schwann cells, and as part of EZR and AHNAK-containing complexes in eye lens fiber cells. Required for the maintenance of the peripheral myelin sheath that is essential for normal transmission of nerve impulses and normal perception of sensory stimuli. Required for normal transport of MBP mRNA from the perinuclear to the paranodal regions. Required for normal remyelination after nerve injury. Required for normal elongation of Schwann cells and normal length of the internodes between the nodes of Ranvier. The demyelinated nodes of Ranvier permit saltatory transmission of nerve impulses; shorter internodes cause slower transmission of nerve impulses. Required for the formation of appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane; the Schwann cell cytoplasm is restricted to regions between these appositions. Required for the formation of Cajal bands and of Schmidt-Lanterman incisures that correspond to short, cytoplasm-filled regions on myelinated nerves. Recruits DRP2 to the Schwann cell plasma membrane. Required for normal protein composition of the eye lens fiber cell plasma membrane and normal eye lens fiber cell morphology","subcellular_location":"Cell membrane; Cell junction","url":"https://www.uniprot.org/uniprotkb/Q9BXM0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PRX","classification":"Not Classified","n_dependent_lines":13,"n_total_lines":1208,"dependency_fraction":0.01076158940397351},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PRX","total_profiled":1310},"omim":[{"mim_id":"619862","title":"SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 32; SCAR32","url":"https://www.omim.org/entry/619862"},{"mim_id":"617583","title":"SULFIREDOXIN 1; SRXN1","url":"https://www.omim.org/entry/617583"},{"mim_id":"614895","title":"CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4F; CMT4F","url":"https://www.omim.org/entry/614895"},{"mim_id":"605725","title":"PERIAXIN; PRX","url":"https://www.omim.org/entry/605725"},{"mim_id":"604769","title":"PEROXIREDOXIN 3; PRDX3","url":"https://www.omim.org/entry/604769"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Vesicles","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lung","ntpm":33.7}],"url":"https://www.proteinatlas.org/search/PRX"},"hgnc":{"alias_symbol":["KIAA1620"],"prev_symbol":[]},"alphafold":{"accession":"Q9BXM0","domains":[{"cath_id":"2.30.42.10","chopping":"17-103","consensus_level":"medium","plddt":77.761,"start":17,"end":103}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXM0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXM0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXM0-F1-predicted_aligned_error_v6.png","plddt_mean":35.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PRX","jax_strain_url":"https://www.jax.org/strain/search?query=PRX"},"sequence":{"accession":"Q9BXM0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BXM0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BXM0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXM0"}},"corpus_meta":[{"pmid":"18501712","id":"PMC_18501712","title":"A novel 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Identification of a novel thiol peroxidase (Prx/Grx) fueled by glutathione amide redox cycling.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11399772","citation_count":47,"is_preprint":false},{"pmid":"16290204","id":"PMC_16290204","title":"T lymphocytes and dendritic cells are activated by the deletion of peroxiredoxin II (Prx II) gene.","date":"2005","source":"Immunology letters","url":"https://pubmed.ncbi.nlm.nih.gov/16290204","citation_count":43,"is_preprint":false},{"pmid":"15694490","id":"PMC_15694490","title":"Biochemical characterization of Toxoplasma gondii 1-Cys peroxiredoxin 2 with mechanistic similarities to typical 2-Cys Prx.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15694490","citation_count":39,"is_preprint":false},{"pmid":"21989804","id":"PMC_21989804","title":"The effects of PRX-07034, a novel 5-HT6 antagonist, on cognitive flexibility and working memory 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sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32329817","citation_count":10,"is_preprint":false},{"pmid":"14745159","id":"PMC_14745159","title":"Distribution of Prx-linked hydroperoxide reductase activity among microorganisms.","date":"2004","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14745159","citation_count":9,"is_preprint":false},{"pmid":"31545198","id":"PMC_31545198","title":"Peroxiredoxin (2-cys-prx) and catalase (katA) cyanobacterial-based bioluminescent bioreporters to detect oxidative stress in the aquatic environment.","date":"2019","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/31545198","citation_count":9,"is_preprint":false},{"pmid":"37468052","id":"PMC_37468052","title":"The PRX-1/TLR4 axis promotes hypoxia-induced radiotherapy resistance in non-small cell lung cancer by targeting the NF-κB/p65 pathway.","date":"2023","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/37468052","citation_count":8,"is_preprint":false},{"pmid":"39366472","id":"PMC_39366472","title":"Cisplatin induces kidney damage through the down-regulation of Prx I by autophagic degradation.","date":"2024","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/39366472","citation_count":8,"is_preprint":false},{"pmid":"36290675","id":"PMC_36290675","title":"Grass Carp Prx 3 Elevates Host Antioxidant Activity and Induces Autophagy to Inhibit Grass Carp Reovirus (GCRV) Replication.","date":"2022","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36290675","citation_count":8,"is_preprint":false},{"pmid":"25628743","id":"PMC_25628743","title":"Novel Compound Heterozygous Nonsense PRX Mutations in a Korean Dejerine-Sottas Neuropathy Family.","date":"2014","source":"Journal of clinical neurology (Seoul, Korea)","url":"https://pubmed.ncbi.nlm.nih.gov/25628743","citation_count":8,"is_preprint":false},{"pmid":"19556853","id":"PMC_19556853","title":"Production and radioimmunoimaging of novel fully human phage display recombinant antibodies and growth inhibition of lung adenocarcinoma cell line overexpressing Prx I.","date":"2009","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/19556853","citation_count":8,"is_preprint":false},{"pmid":"37127188","id":"PMC_37127188","title":"Molecular cloning and functional characterization of peroxiredoxin 4 (prx 4) in freshwater crayfish, Procambarus clarkii.","date":"2023","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/37127188","citation_count":7,"is_preprint":false},{"pmid":"21458419","id":"PMC_21458419","title":"Proteomic identification of an embryo-specific 1Cys-Prx promoter and analysis of its activity in transgenic rice.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21458419","citation_count":7,"is_preprint":false},{"pmid":"39457369","id":"PMC_39457369","title":"Molecular Characterization of Peroxidase (PRX) Gene Family in Cucumber.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/39457369","citation_count":6,"is_preprint":false},{"pmid":"33669127","id":"PMC_33669127","title":"Maturation of Mitochondrially Targeted Prx V Involves a Second Cleavage by Mitochondrial Intermediate Peptidase That Is Sensitive to Inhibition by H2O2.","date":"2021","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/33669127","citation_count":6,"is_preprint":false},{"pmid":"25429515","id":"PMC_25429515","title":"Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects.","date":"2015","source":"Canadian journal of physiology and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25429515","citation_count":6,"is_preprint":false},{"pmid":"35855475","id":"PMC_35855475","title":"Comprehensive identification, evolutionary patterns and the divergent response of PRX genes in Phaseolus vulgaris under biotic and abiotic interactions.","date":"2022","source":"3 Biotech","url":"https://pubmed.ncbi.nlm.nih.gov/35855475","citation_count":5,"is_preprint":false},{"pmid":"37470010","id":"PMC_37470010","title":"Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review.","date":"2023","source":"Frontiers in neurology","url":"https://pubmed.ncbi.nlm.nih.gov/37470010","citation_count":4,"is_preprint":false},{"pmid":"39761879","id":"PMC_39761879","title":"Genome-wide analysis of Class III peroxidase (PRX) family core genes and functional mechanism of GhPRXR1-A for seed development in Gossypium hirsutum.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39761879","citation_count":4,"is_preprint":false},{"pmid":"20222976","id":"PMC_20222976","title":"The influence of a pre-exercise sports drink (PRX) on factors related to maximal aerobic performance.","date":"2010","source":"Journal of the International Society of Sports Nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/20222976","citation_count":4,"is_preprint":false},{"pmid":"39776216","id":"PMC_39776216","title":"The Trx-Prx redox pathway and PGR5/PGRL1-dependent cyclic electron transfer play key regulatory roles in poplar drought stress.","date":"2025","source":"Tree physiology","url":"https://pubmed.ncbi.nlm.nih.gov/39776216","citation_count":3,"is_preprint":false},{"pmid":"35696080","id":"PMC_35696080","title":"Bioinformatic Analyses of Peroxiredoxins and RF-Prx: A Random Forest-Based Predictor and Classifier for Prxs.","date":"2022","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/35696080","citation_count":3,"is_preprint":false},{"pmid":"38637880","id":"PMC_38637880","title":"Exploring the role of Prx II in mitigating endoplasmic reticulum stress and mitochondrial dysfunction in neurodegeneration.","date":"2024","source":"Cell communication and signaling : CCS","url":"https://pubmed.ncbi.nlm.nih.gov/38637880","citation_count":3,"is_preprint":false},{"pmid":"40705350","id":"PMC_40705350","title":"Intravenous Delivery of Long-Acting Dnase I (PRX-119) In a Murine Model of Polymicrobial Abdominal Sepsis.","date":"2025","source":"Shock (Augusta, Ga.)","url":"https://pubmed.ncbi.nlm.nih.gov/40705350","citation_count":2,"is_preprint":false},{"pmid":"34749598","id":"PMC_34749598","title":"Oxidative Stress Induced Cell Cycle Arrest: Potential Role of PRX-2 and GSTP-1 as Therapeutic Targets in Hepatocellular Carcinoma.","date":"2021","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/34749598","citation_count":2,"is_preprint":false},{"pmid":"40588199","id":"PMC_40588199","title":"Evaluation of intracellularly targeted engineered antioxidant fusion proteins SOD-LCA2 and Prx-LCA2 as promising therapeutic combinations for alleviating and restoring pulmonary oxidative damage.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40588199","citation_count":2,"is_preprint":false},{"pmid":"31571930","id":"PMC_31571930","title":"Erratum: β-elemene inhibits radiation and hypoxia-induced macrophages infiltration via Prx-1/NF-κB/HIF-1α signaling pathway [Corrigendum].","date":"2019","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/31571930","citation_count":2,"is_preprint":false},{"pmid":"40501931","id":"PMC_40501931","title":"Inhibition of peroxisomal protein PRX-11 promotes longevity in Caenorhabditis elegans via enhancements to mitochondria.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40501931","citation_count":1,"is_preprint":false},{"pmid":"40722921","id":"PMC_40722921","title":"Identification of Peroxiredoxin (PRX) Genes from Pepper Fruits: Involvement in Ripening and Modulation by Nitric Oxide (NO).","date":"2025","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/40722921","citation_count":1,"is_preprint":false},{"pmid":"29574296","id":"PMC_29574296","title":"Novel prodrug PRX-P4-003, selectively activated by gut enzymes, may reduce the risk of iatrogenic addiction and abuse.","date":"2018","source":"Drug and alcohol dependence","url":"https://pubmed.ncbi.nlm.nih.gov/29574296","citation_count":1,"is_preprint":false},{"pmid":"30070795","id":"PMC_30070795","title":"[Effects of PRX-2 gene on the phenotype changes of epidermal stem cells differentiating into sweat gland cells].","date":"2017","source":"Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery","url":"https://pubmed.ncbi.nlm.nih.gov/30070795","citation_count":1,"is_preprint":false},{"pmid":"37991495","id":"PMC_37991495","title":"Systematic analysis of Prx genes in the Brachypodium genus and their expression pattern under abiotic constraints.","date":"2023","source":"Plant biology (Stuttgart, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/37991495","citation_count":0,"is_preprint":false},{"pmid":"42188596","id":"PMC_42188596","title":"Thermostable Oxidoreductases CotA and Prx Enable Synergistic and Peroxide-Enhanced Degradation of Aflatoxin B1.","date":"2026","source":"Toxins","url":"https://pubmed.ncbi.nlm.nih.gov/42188596","citation_count":0,"is_preprint":false},{"pmid":"29227081","id":"PMC_29227081","title":"Prx II and CKBB proteins interaction under physiologic al and thermal stress conditions in A549 and HeLa cells.","date":"2016","source":"Ukrainian biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/29227081","citation_count":0,"is_preprint":false},{"pmid":"40531438","id":"PMC_40531438","title":"Engineered Prx-LCA2 fusion protein restores oxidative skin damage via enhanced intracellular peroxidase delivery.","date":"2025","source":"AMB Express","url":"https://pubmed.ncbi.nlm.nih.gov/40531438","citation_count":0,"is_preprint":false},{"pmid":"40763090","id":"PMC_40763090","title":"Inflammatory Mediators Related to Vascular Dysfunction are Linked to ICP, PRx, and CPP Following Human Severe Traumatic Brain Injury.","date":"2025","source":"Journal of neurotrauma","url":"https://pubmed.ncbi.nlm.nih.gov/40763090","citation_count":0,"is_preprint":false},{"pmid":"35810435","id":"PMC_35810435","title":"[Analysis of PRX gene variants in a child with Charcot-Marie-Tooth disease type 4F].","date":"2022","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35810435","citation_count":0,"is_preprint":false},{"pmid":"23269909","id":"PMC_23269909","title":"Effect of PRX-1 Downregulation in the Type 1 Diabetes Microenvironment.","date":"2012","source":"The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/23269909","citation_count":0,"is_preprint":false},{"pmid":"40885294","id":"PMC_40885294","title":"Pc-prx 6 plays an important role in the regulation of antibacterial innate immune in the hepatopancreas of Procambarus clarkii due to its potential antioxidant capacity.","date":"2025","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40885294","citation_count":0,"is_preprint":false},{"pmid":"42045832","id":"PMC_42045832","title":"Genome-wide identification and alkaline stress response analysis of the class III peroxidase (PRX) gene family in Castanea mollissima.","date":"2026","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/42045832","citation_count":0,"is_preprint":false},{"pmid":"41230902","id":"PMC_41230902","title":"Abnormal Splicing in the Final Intron of PRX Results in Dominant Congenital Cataract Without Neurological Phenotype.","date":"2025","source":"Investigative ophthalmology & visual science","url":"https://pubmed.ncbi.nlm.nih.gov/41230902","citation_count":0,"is_preprint":false},{"pmid":"22321921","id":"PMC_22321921","title":"[Effect of PRX-2 gene transferred by lipofectamine on the proliferation of human skin fibroblasts].","date":"2011","source":"Zhonghua yi xue za zhi","url":"https://pubmed.ncbi.nlm.nih.gov/22321921","citation_count":0,"is_preprint":false},{"pmid":"41151426","id":"PMC_41151426","title":"Development of peroxidase-modified zeolite carbon paste electrodes (Prx-Zeo/CPE) for the biosensing of hydroquinone in pharmaceutical skin cream.","date":"2025","source":"Bioelectrochemistry (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/41151426","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.25.25334410","title":"Genomic insights into population stratification, biological adaptation, and archaic introgression at the crossroads of the Himalayas and lowland East Asia","date":"2025-08-28","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.25.25334410","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.28.656437","title":"Inhibition of peroxisomal protein PRX-11 promotes longevity in  <i>Caenorhabditis elegans</i>  via enhancements to mitochondria","date":"2025-05-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.28.656437","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.04.24318244","title":"PRX-3140, a 5-HT4 Partial Agonist and Sigma-1 Agonist/Antagonist, Modulates Glucocorticoid Insulin Suppression and Cortisol Levels","date":"2024-12-05","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.04.24318244","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.02.605684","title":"The phage protein paratox is a multifunctional metabolic regulator of  <i>Streptococcus</i>","date":"2024-08-02","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.02.605684","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.30.620562","title":"Screening of potential biomarkers using activity-based protein profiling in a rat model of chemotherapy-induced peripheral neuropathy","date":"2024-11-01","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.30.620562","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.17.633690","title":"Differential regulation of brain-specific molecular pathways is the reason for curcumin’s adult life-phase specific DAergic neuroprotection: Insights from ALSS Drosophila model of Parkinson’s disease","date":"2025-01-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.17.633690","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48112,"output_tokens":2047,"usd":0.087521,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8572,"output_tokens":2126,"usd":0.048005,"stage2_stop_reason":"end_turn"},"total_usd":0.135526,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the corpus, I need to identify which papers are about the human gene PRX (HGNC: PRX, also known as KIAA1620), which encodes **periaxin** — a PDZ-domain-containing protein involved in peripheral nerve myelin maintenance.\n\nMany papers in this corpus use \"PRX\" or \"Prx\" as abbreviations for **peroxiredoxin** (a completely different protein family), or for pharmaceutical compounds (PRX-00023, PRX-07034, etc.), or for plant/bacterial class III peroxidases. I must exclude all of these.\n\nPapers about **periaxin (PRX/KIAA1620)**:\n- PMID:29968755 — PRX (periaxin) in cerebrovascular endothelial cells, PDZ domain function\n- PMID:27081207 — PRX variant in congenital cataract\n- PMID:21741241 — PRX mutations in CMT4F\n- PMID:16534116 — PRX mutations in CMT4F\n- PMID:18504680 — PRX mutations in CMT4F\n- PMID:25628743 — PRX mutations in DSN\n- PMID:36833258 — PRX mutations in CMT4F\n- PMID:37470010 — PRX mutations and CMT4F review\n- PMID:35810435 — PRX variants in CMT4F\n- PMID:41230902 — PRX splicing variants and congenital cataract\n\nNow extracting mechanistic discoveries:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Periaxin (PRX) is expressed in human cerebral endothelial cells (but not in brain endothelium of other mammalian species), where it localizes predominantly to the nucleus. Overexpression of PRX in mouse endothelial cells strengthens barrier function, significantly increases transendothelial electrical resistance (~35%), and reduces permeability of a wide range of molecules. The PDZ domain of PRX is necessary and sufficient for these barrier-enhancing properties, as a splice variant (S-PRX) containing only the PDZ domain also increases barrier function. PRX expression also suppresses a panel of inflammatory markers (predominantly Type I interferon response genes) by at least 50%.\",\n      \"method\": \"Transcriptome analysis, transendothelial electrical resistance measurement, permeability assays, overexpression of full-length PRX and PDZ-only splice variant (S-PRX) in mouse endothelial cells, immunofluorescence localization\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal functional assays (TER, permeability, transcriptomics, domain dissection) in a single lab; no independent replication\",\n      \"pmids\": [\"29968755\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Splicing defects in the final intron of PRX (intron 6 of PRXb/L-PRX) cause dominant congenital cataract. Variants within the splice region cause aberrant splicing confirmed by RNA sequencing, including intron 6 retention (switching expression to the S-PRX isoform) and/or use of alternate donor/acceptor sites yielding small in-frame deletions in L-PRX. Loss-of-function variants affecting L-PRX (or both isoforms) cause recessive neurological phenotypes without cataract, whereas dominant cataract results specifically from disruption of L-PRX splicing, possibly through a gain-of-function or dominant-negative mechanism. PRX is thus necessary for proper organization of the lens cortex adherens junction.\",\n      \"method\": \"Exome and genome sequencing, RNA sequencing to confirm aberrant splicing in affected individuals from four families, isoform analysis\",\n      \"journal\": \"Investigative ophthalmology & visual science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA-seq confirmation of aberrant splicing in multiple families with orthogonal sequencing methods; single study, no functional reconstitution\",\n      \"pmids\": [\"41230902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"A novel frameshift mutation (S399fsX410) in the PRX gene produces a truncated periaxin protein lacking the C-terminal domain, causing early-onset Charcot-Marie-Tooth type 4F (CMT4F) demyelinating neuropathy. This establishes that the C-terminal region of periaxin is required for normal peripheral nerve myelin maintenance.\",\n      \"method\": \"Genetic sequencing of PRX gene in CMT4F patient, protein-level analysis of truncation effect\",\n      \"journal\": \"Neurology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single patient genetic identification with protein-level characterization; no functional reconstitution or mechanistic dissection beyond mutation identification\",\n      \"pmids\": [\"16534116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Novel homozygous nonsense mutation in PRX (c.1090C>T, p.Arg364X) causes CMT4F with a late-onset and relatively benign clinical course, broadening the genotype-phenotype spectrum. PRX mutations cause severe demyelination of peripheral nerves with focally folded myelin on nerve biopsy, establishing PRX as required for normal myelin architecture.\",\n      \"method\": \"Genetic sequencing, nerve biopsy histopathology\",\n      \"journal\": \"Neuromuscular disorders : NMD\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic identification with histopathological phenotype; no molecular mechanistic experiment\",\n      \"pmids\": [\"21741241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"A novel homozygous PRX mutation (A700PfsX17) causes early-onset demyelinating autosomal recessive CMT with severe sensory loss and sensory ataxia, establishing that PRX function is required for sensory as well as motor peripheral nerve myelin maintenance.\",\n      \"method\": \"Genetic sequencing of PRX gene in a consanguineous family with early-onset CMT\",\n      \"journal\": \"Neuropediatrics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic identification; no molecular mechanistic experiment beyond mutation-phenotype linkage\",\n      \"pmids\": [\"18504680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Compound heterozygous nonsense mutations in PRX (p.R392X and p.R679X) cause Dejerine-Sottas neuropathy (DSN) with early-onset slowly progressive demyelinating neuropathy and prominent sensory involvement, demonstrating that biallelic loss-of-function of periaxin is sufficient to cause severe demyelinating peripheral neuropathy.\",\n      \"method\": \"Whole-exome sequencing, capillary sequencing, co-segregation analysis\",\n      \"journal\": \"Journal of clinical neurology (Seoul, Korea)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic identification with clinical phenotyping; no biochemical or cell biological mechanistic experiment\",\n      \"pmids\": [\"25628743\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Periaxin (PRX), a PDZ-domain-containing protein encoded by the PRX/KIAA1620 gene, is required for maintenance of peripheral nerve myelin (loss-of-function mutations cause autosomal recessive CMT4F/Dejerine-Sottas demyelinating neuropathy); in human cerebral endothelial cells PRX localizes predominantly to the nucleus and its PDZ domain is necessary and sufficient to strengthen endothelial barrier function and suppress interferon-response inflammatory gene expression; isoform-specific splicing defects that replace L-PRX with S-PRX disrupt lens cortex adherens junction organization and cause dominant congenital cataract through a mechanism distinct from the recessive neurological phenotype.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Periaxin (PRX) is a PDZ-domain-containing protein required for the maintenance of peripheral nerve myelin, where biallelic loss-of-function mutations cause early-onset demyelinating Charcot-Marie-Tooth type 4F and Dejerine-Sottas neuropathy with prominent sensory and motor involvement and focally folded myelin on nerve biopsy [#3, #5]. Truncations that remove the C-terminal region of the long isoform (L-PRX) abolish normal myelin architecture, establishing that this domain is essential for peripheral nerve function [#2, #4]. The PRX locus produces distinct isoforms with separable functions: in human cerebral endothelial cells PRX localizes predominantly to the nucleus, where its PDZ domain is necessary and sufficient to strengthen endothelial barrier integrity and suppress Type I interferon-response inflammatory genes [#0]. Isoform-specific splicing defects in the final intron of L-PRX—causing intron retention that switches expression to the PDZ-only S-PRX isoform or small in-frame deletions—disrupt lens cortex adherens junction organization and cause dominant congenital cataract through a mechanism distinct from the recessive neurological phenotype [#1]. Beyond these genetic and barrier-function findings, the molecular partners and biochemical activity of periaxin have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that the C-terminal region of periaxin is required for peripheral nerve myelin maintenance by linking a frameshift truncation to demyelinating neuropathy.\",\n      \"evidence\": \"Genetic sequencing and protein-level truncation analysis in a CMT4F patient\",\n      \"pmids\": [\"16534116\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single patient without functional reconstitution\", \"No mechanistic dissection of how C-terminal loss disrupts myelin\", \"Molecular partners of the C-terminal domain unidentified\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Extended periaxin's required role to sensory as well as motor peripheral nerve myelin, showing the deficit is not motor-restricted.\",\n      \"evidence\": \"Genetic sequencing of a homozygous frameshift variant in a consanguineous early-onset CMT family\",\n      \"pmids\": [\"18504680\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Genotype-phenotype linkage only, no molecular experiment\", \"Mechanism of sensory fiber vulnerability unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Broadened the clinical spectrum of PRX loss to late-onset benign neuropathy and tied PRX deficiency to focally folded myelin architecture on biopsy.\",\n      \"evidence\": \"Genetic sequencing and nerve biopsy histopathology of a homozygous nonsense variant\",\n      \"pmids\": [\"21741241\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No molecular mechanistic experiment\", \"Basis for variable onset/severity unexplained\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated that biallelic loss-of-function of periaxin is sufficient to cause severe Dejerine-Sottas demyelinating neuropathy, consolidating the recessive loss-of-function model.\",\n      \"evidence\": \"Whole-exome and capillary sequencing with co-segregation analysis of compound heterozygous nonsense variants\",\n      \"pmids\": [\"25628743\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No biochemical or cell-biological mechanism\", \"Downstream effectors in Schwann cell myelination unidentified\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed a non-neural function for PRX: nuclear localization in human cerebral endothelial cells where its PDZ domain enhances barrier integrity and suppresses interferon-response inflammation.\",\n      \"evidence\": \"Transcriptomics, transendothelial resistance and permeability assays, and PDZ-only (S-PRX) domain dissection by overexpression in mouse endothelial cells\",\n      \"pmids\": [\"29968755\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, no independent replication\", \"Nuclear mechanism by which a PDZ domain strengthens barrier function unresolved\", \"Direct interaction partners and target transcription circuit unidentified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Distinguished isoform-specific pathology: disruption of L-PRX splicing (intron retention favoring S-PRX or in-frame deletions) causes dominant congenital cataract via lens adherens junction disorganization, mechanistically separate from recessive neuropathy.\",\n      \"evidence\": \"Exome/genome and RNA sequencing confirming aberrant splicing across four cataract families\",\n      \"pmids\": [\"41230902\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional reconstitution of the dominant-negative/gain-of-function mechanism\", \"Molecular basis of L-PRX's role at lens adherens junctions undefined\", \"Single study\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular partners, biochemical activity, and the structural basis by which the PDZ and C-terminal domains organize junctions and myelin remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No identified direct physical interactors\", \"No structural model linking domain function to junction or myelin organization\", \"Mechanism reconciling nuclear endothelial role with junctional/myelin roles unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":4,"faith_total":4,"faith_pct":100.0}}