Affinage

RPGR

X-linked retinitis pigmentosa GTPase regulator · UniProt Q92834

Length
1020 aa
Mass
113.4 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPGR is a ciliary scaffold protein essential for polarized protein trafficking across the photoreceptor connecting cilium, whose loss causes mislocalization of rhodopsin, cone opsins, and other ciliary proteins, leading to photoreceptor degeneration and X-linked retinitis pigmentosa (RP3) (PMID:8673101, PMID:10725384, PMID:30924157). Its N-terminal RCC1-like β-propeller domain mediates ciliary/centrosomal targeting and serves as a docking platform for PDE6δ, which delivers prenylated cargo to cilia; structural studies show RPGR binds cargo-loaded PDE6δ and exposes its Arl2/Arl3-binding site, facilitating GTPase-triggered release of lipidated proteins into the ciliary compartment (PMID:23559067, PMID:27493202, PMID:30622176). The photoreceptor-predominant RPGR-ORF15 isoform contains a Glu-Gly-rich repetitive region that is specifically glutamylated by TTLL5 via recognition of the C-terminal basic domain; loss of this modification phenocopies RPGR deficiency, and distal ORF15 truncations that disrupt TTLL5 binding shift disease from rod-cone to cone-dominated dystrophy (PMID:27162334, PMID:36445968). RPGR also regulates actin cytoskeletal dynamics through RhoA signaling and selectively controls the composition of soluble proteins within photoreceptor sensory cilia, with its loss increasing RhoA-GTP and F-actin levels prior to degeneration onset (PMID:21933838, PMID:26908598, PMID:26068394).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Positional cloning identified RPGR as the RP3 gene, revealing an RCC1-like domain that suggested GTPase-regulatory function and a C-terminal isoprenylation motif, establishing the molecular identity of a major X-linked retinitis pigmentosa locus.

    Evidence Positional cloning with mutation screening in RP3 families

    PMID:8673101

    Open questions at the time
    • No GTPase partner identified
    • Subcellular localization unknown
    • Function of the RCC1-like domain not demonstrated
  2. 2000 High

    Knockout mouse studies and immunolocalization resolved where RPGR acts — the photoreceptor connecting cilium — and showed that its absence causes cone opsin mislocalization and degeneration, establishing RPGR as a gatekeeper of polarized protein trafficking across this structure.

    Evidence Rpgr knockout mice with immunofluorescence, EM, and ERG

    PMID:10725384

    Open questions at the time
    • Mechanism of opsin mislocalization unknown
    • Direct trafficking versus scaffolding role not distinguished
  3. 2000 High

    Identification of RPGRIP1 as a direct binding partner provided the first evidence of an RPGR protein interaction network at the ciliary transition zone.

    Evidence Yeast two-hybrid screen of bovine retinal library with co-IP confirmation

    PMID:10958647

    Open questions at the time
    • Functional consequence of RPGR–RPGRIP1 interaction not tested
    • In vivo validation pending
  4. 2002 High

    Discovery of extensive alternative splicing and the photoreceptor-predominant ORF15 exon explained why most disease mutations cluster in a single exon and defined the functionally critical isoform.

    Evidence RT-PCR, RACE, minigene splicing assays

    PMID:12407146

    Open questions at the time
    • Functional difference between isoforms not tested in vivo
    • Post-translational modification of ORF15 region unknown
  5. 2004 Medium

    Transgenic expression of truncated RPGR-ORF15 revealed that certain truncation mutants are dominant-negative gain-of-function alleles, more toxic than null, indicating that RPGR misfolded fragments actively poison photoreceptor function.

    Evidence Transgenic mice on WT and Rpgr-null backgrounds with ERG and histology

    PMID:14691151

    Open questions at the time
    • Toxic mechanism not identified
    • Whether this applies to human frameshift mutations unknown
  6. 2005 High

    Proteomic and interaction studies placed RPGR-ORF15 in a complex with axonemal and motor proteins (SMC1/3, IFT88, KIF3A, dynein components), showing that its basal body localization depends on dynein-mediated transport and that the RCC1-like domain mediates key interactions.

    Evidence MS of immunoprecipitated retinal axonemes, pulldown assays, dominant-negative p50-dynamitin in cells

    PMID:15772089 PMID:16043481

    Open questions at the time
    • Whether SMC1/3 interaction is structural or regulatory unclear
    • Direct role of IFT88 association not tested
  7. 2005 High

    In vivo rescue of Rpgr-null mice with a truncated ORF15 transgene demonstrated that the ORF15 isoform is the functionally relevant form in photoreceptors and that the repetitive region tolerates partial deletion.

    Evidence Transgenic rescue in Rpgr-knockout mice with ERG, opsin localization, histology

    PMID:15671266

    Open questions at the time
    • Minimum required length of repetitive region not defined
    • Whether glutamylation is needed for rescue unknown at this point
  8. 2011 Medium

    RPGR knockdown in RPE cells linked RPGR to ciliogenesis and actin cytoskeletal regulation via integrin/FAK/RhoA signaling, extending its role beyond opsin trafficking to broader cellular processes.

    Evidence siRNA knockdown in hTERT-RPE1 cells with adhesion, cilia counting, and signaling assays

    PMID:21933838

    Open questions at the time
    • Direct versus indirect effect on actin not resolved
    • Relevance to photoreceptor-specific pathology uncertain
  9. 2013 High

    Crystal structures of the RPGR propeller domain alone and in complex with PDE6δ provided atomic-level understanding of how RPGR scaffolds cargo-loaded PDE6δ and exposes the Arl2/Arl3 binding site, establishing a mechanism for GTPase-regulated release of lipidated proteins into cilia.

    Evidence X-ray crystallography of RPGR and RPGR–PDE6δ complex, biochemical binding assays

    PMID:23559067

    Open questions at the time
    • In vivo cargo identity not determined
    • Whether Arl3 forms a ternary complex with RPGR–PDE6δ not shown structurally
  10. 2015 Medium

    Proteomic analysis of isolated photoreceptor cilia from Rpgr-knockout mice revealed selective changes in soluble proteins (proteasomal and vesicular trafficking components) rather than structural proteins, indicating RPGR acts as a gatekeeper for specific cargo classes.

    Evidence Tandem MS of purified photoreceptor sensory cilia from KO mouse

    PMID:26068394

    Open questions at the time
    • Direct substrates of RPGR-mediated transport not identified
    • Whether changes are cause or consequence of early dysfunction unclear
  11. 2016 High

    Identification of TTLL5 as the specific glutamylase for RPGR-ORF15 — binding via the C-terminal basic domain — and demonstration that Ttll5 mutant mice phenocopy Rpgr loss established glutamylation as an essential post-translational modification for RPGR function.

    Evidence In vitro glutamylation assays, Ttll5 mutant mouse, domain-binding experiments, human disease variant analysis

    PMID:27162334

    Open questions at the time
    • How glutamylation alters RPGR interactions or function mechanistically unknown
    • Reader proteins for RPGR glutamylation not identified
  12. 2016 Medium

    Transcriptomic and biochemical analyses in Rpgr-knockout retinas showed elevated RhoA-GTP and F-actin prior to degeneration, directly linking RPGR loss to actin cytoskeletal dysregulation in rods, while cone-specific effects involved visual cycle gene dysregulation.

    Evidence Transcriptomics, RhoA-GTP pulldown, F-actin quantification in Rpgr KO and Rpgr KO/Nrl KO mice

    PMID:26908598

    Open questions at the time
    • Direct molecular link between RPGR and RhoA pathway not identified
    • Whether actin dysregulation is a primary cause of degeneration unclear
  13. 2016 Medium

    Demonstration that RPGR1-19 is prenylated and trafficked to cilia by PDE6D, with two independent ciliary targeting signals (RCC1-like domain and C-terminal prenylation site), resolved the mechanism by which RPGR itself reaches its site of action.

    Evidence Prenylation mutant constructs, PDE6D siRNA, ciliary localization in cultured cells

    PMID:27493202

    Open questions at the time
    • Whether ORF15 isoform uses the same trafficking mechanism unclear
    • In vivo validation of dual targeting signals lacking
  14. 2019 Medium

    Mapping of endogenous RPGR interaction network (PDE6D, INPP5E, RPGRIP1L) and showing that pathogenic missense variants disrupt this network unified the molecular basis of diverse RPGR missense mutations as convergent disruption of ciliary protein interactions.

    Evidence Endogenous Co-IP, ciliary localization assays with patient-derived mutants in RPE1 cells

    PMID:30622176

    Open questions at the time
    • Whether all patients' mutations converge on interaction disruption remains untested for frameshifts
    • Quantitative contribution of each interactor to disease not determined
  15. 2022 Medium

    Genotype-phenotype correlation showed that distal ORF15 truncations that disrupt TTLL5 binding and RPGR glutamylation shift disease toward cone-dominated dystrophy, mechanistically linking the C-terminal basic domain, glutamylation status, and cell-type-specific vulnerability.

    Evidence Clinical cohort analysis with Co-IP and glutamylation assays for patient-derived RPGR variants

    PMID:36445968

    Open questions at the time
    • Why cones are preferentially affected by loss of glutamylation unknown
    • Whether glutamylation differentially modulates rod vs. cone interactomes not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identities of lipidated cargo proteins released via RPGR-scaffolded PDE6δ–Arl3 complexes in photoreceptors, the downstream 'readers' of RPGR glutamylation, and the precise mechanism linking RPGR to RhoA-dependent actin regulation remain unknown.
  • In vivo lipidated cargo identity undetermined
  • Glutamylation reader proteins not identified
  • Direct molecular link to RhoA pathway unresolved
  • Whether gene therapy restoring ORF15 fully corrects glutamylation in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005929 cilium 8 GO:0005815 microtubule organizing center 3
Pathway
R-HSA-9709957 Sensory Perception 4 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
CEP290IFT88PDE6DRPGRIP1RPGRIP1LSMC1ASMC3TTLL5

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RPGR was identified as a gene encoding a ~90 kDa protein with an N-terminal RCC1-like tandem repeat domain (homologous to the guanine nucleotide exchange factor for Ran GTPase), suggesting interaction with a small GTPase, and a C-terminal acidic domain ending in a potential isoprenylation site; intragenic deletions and missense mutations within conserved domains establish it as the RP3 disease gene. Positional cloning, genomic sequencing, mutation analysis Nature genetics High 8673101
2000 RPGR localizes to the connecting cilia of rod and cone photoreceptors; RPGR-deficient (knockout) mice exhibit ectopic localization of cone opsins in cell bodies and synapses and reduced rhodopsin levels, followed by photoreceptor degeneration, establishing RPGR's role in maintaining polarized protein distribution across the connecting cilium. Mouse gene knockout, immunofluorescence, light/electron microscopy, electroretinography Proceedings of the National Academy of Sciences of the United States of America High 10725384
2000 RPGRIP1 (RPGR-interacting protein 1) was identified as a novel binding partner of RPGR, discovered by yeast two-hybrid screening of a bovine retinal cDNA library; the interaction was confirmed by co-immunoprecipitation of in vitro translated protein and by RPGR mutant analysis. RPGRIP1 is expressed in retina and testis and contains coiled-coil domains. Yeast two-hybrid, co-immunoprecipitation of in vitro translated proteins, mutant analysis Human molecular genetics High 10958647
2002 RPGR undergoes complex alternative splicing producing multiple isoforms; the photoreceptor-predominant isoform terminates in the purine-rich ORF15 exon. The exceptional transcript heterogeneity results from multiple exonic splicing enhancers (ESEs) in the purine-rich region that interact with SR proteins. RPGR proteins are concentrated in the connecting cilium of photoreceptors. RT-PCR, RACE, minigene transfection, immunoblot, immunocytochemistry Investigative ophthalmology & visual science High 12407146
2005 RPGR-ORF15 localizes to the axoneme, basal bodies of the photoreceptor connecting cilium, and to the tip and axoneme of sperm flagella. Mass spectrometry of immunoprecipitated retinal axoneme fractions identified SMC1 and SMC3 as interacting proteins; pulldown assays demonstrated that this interaction is mediated by the RCC1-like domain of RPGR and requires SMC1 phosphorylation. RPGR-ORF15 also associates with the intraflagellar transport protein IFT88 and microtubule motor proteins KIF3A, p150Glued, and p50-dynamitin; inhibition of dynein by p50-dynamitin overexpression abolished RPGR-ORF15 basal body localization. Immunoprecipitation, mass spectrometry, pulldown assays, overexpression of dominant-negative dynein subunit, immunofluorescence The Journal of biological chemistry High 16043481
2005 The RPGR-ORF15 isoform and RPGRIP1 co-localize at centrioles and basal bodies in cultured mammalian cells throughout the cell cycle, resistant to microtubule depolymerization. Mass spectrometry and yeast two-hybrid identified nucleophosmin (NPM) as an interactor of the conserved C2 domain of RPGR-ORF15; interaction confirmed by binding of recombinant and native NPM to RPGR fusion proteins in vitro and by co-immunoprecipitation from bovine retinal extracts and cultured cells. NPM and RPGR-ORF15 co-localize at metaphase centrosomes. MALDI-TOF mass spectrometry, yeast two-hybrid, in vitro binding assay with recombinant proteins, co-immunoprecipitation from retinal extracts and cultured cells, immunofluorescence, nocodazole treatment Human molecular genetics High 15772089
2005 The RPGR-ORF15 isoform is the functionally relevant variant in photoreceptors; a transgenic mouse expressing an abbreviated ORF15 (shortened repetitive region) in an RPGR-null background showed RPGR localization to connecting cilia and substantial rescue of photoreceptor morphology, opsin localization, and ERG responses, demonstrating the repetitive purine-rich region can be partially deleted without ablating function. Transgenic rescue in RPGR-knockout mice, immunofluorescence, ERG, histology Investigative ophthalmology & visual science High 15671266
2007 RPGR isoforms (RPGR1-19 and RPGRORF15) localize to distinct sub-cellular compartments in mammalian photoreceptors; the RCC1-like domain of RPGR is sufficient to target it to cilia and centrosomes in cultured cells. RPGR isoforms associate with cilia-centrosomal proteins demonstrated by sucrose-gradient centrifugation and co-immunoprecipitation. Isoform-specific antibodies, sucrose-gradient centrifugation, immunofluorescence, co-immunoprecipitation, transfection of domain constructs Vision research Medium 17904189
2011 RPGR knockdown in human retinal pigment epithelium cells (hTERT-RPE1) resulted in reduced cilia number, slower cell cycle progression, impaired fibronectin attachment, stronger actin stress filaments, dysregulated Akt/Erk1/2/FAK/Src signaling, and reduced β1-integrin at the cell surface, establishing a role for RPGR in cilia formation and regulation of actin cytoskeletal dynamics. RNAi knockdown, cilia counting, wound-healing assay, fibronectin adhesion assay, western blot for signaling pathways, flow cytometry Human molecular genetics Medium 21933838
2013 Crystal structure of the RPGR RCC1-like propeller domain revealed the location of patient mutations and how they perturb the structure. The RPGR–PDEδ complex structure showed PDEδ binding to a highly conserved surface patch of RPGR. Biochemical experiments showed RPGR binds with high affinity to cargo-loaded PDEδ and exposes the Arl2/Arl3-binding site on PDEδ, supporting a model where RPGR acts as a scaffold recruiting cargo-loaded PDEδ and Arl3 to release lipidated cargo into cilia. X-ray crystallography of RPGR propeller domain and RPGR–PDEδ complex, biochemical binding assays EMBO reports High 23559067
2016 TTLL5 glutamylates RPGR-ORF15 in its Glu-Gly-rich repetitive region (which contains motifs homologous to the α-tubulin C-terminal tail); the C-terminal basic domain of RPGR-ORF15 binds the noncatalytic cofactor-interaction domain of TTLL5 and targets TTLL5 to glutamylate RPGR. Only TTLL5 (not other TTLL family members) interacts with RPGR-ORF15. A Ttll5 mutant mouse shows complete loss of RPGR glutamylation without marked changes in tubulin glutamylation, and develops cone opsin mislocalization and slow photoreceptor degeneration resembling Rpgr-null mice. TTLL5 disease mutants causing human retinal dystrophy show impaired RPGR-ORF15 glutamylation. In vitro glutamylation assay, co-immunoprecipitation of transiently expressed proteins, Ttll5 mutant mouse model, domain-binding experiments, mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 27162334
2016 Loss of RPGR in a rod-dominant (Rpgr knockout) mouse retina leads to predominant alterations in genes involved in actin cytoskeletal dynamics, with increased activated RhoA-GTP and polymerized F-actin prior to degeneration onset. In Rpgr-knockout::Nrl-null (all-cone) mice, loss of RPGR primarily causes up-regulation of RPE-specific genes associated with the visual cycle, indicating RPGR differentially affects rod versus cone intracellular pathways. Transcriptomic analysis, RhoA activity assay (RhoA-GTP pull-down), F-actin quantification, double-knockout mouse generation Human molecular genetics Medium 26908598
2016 RPGR constitutive isoform (RPGR1-19) is prenylated; its ciliary targeting requires prenylation. Two independent ciliary targeting signals exist in RPGR: one within the N-terminal RCC1-like domain and one near the C-terminal prenylation site. Ablation of PDE6D blocks ciliary targeting of RPGR, demonstrating RPGR is a cargo of PDE6D for ciliary trafficking. Prenylation mutant constructs, PDE6D siRNA knockdown, immunofluorescence for ciliary localization Biology open Medium 27493202
2016 RPGR physically interacts with the C-terminal domain of CEP290, and heterozygous hypomorphic Cep290 allele (but not null allele) accelerates retinal degeneration onset and worsens opsin mislocalization in Rpgr-knockout mice, demonstrating genetic interaction between RPGR and CEP290 in modifying photoreceptor ciliopathy severity. Co-immunoprecipitation (physical interaction), double-mutant mouse models (epistasis/modifier analysis), immunohistochemistry, ERG Human molecular genetics Medium 26936822
2015 Ablation of RPGR in photoreceptors alters the composition of photoreceptor sensory cilia, specifically affecting levels of proteins involved in proteasomal function and vesicular trafficking, as well as high-molecular-weight soluble proteins, prior to degeneration onset; structural and phototransduction proteins are not significantly altered, indicating RPGR selectively regulates entry or retention of soluble proteins in photoreceptor cilia. Tandem mass spectrometry of isolated photoreceptor sensory cilia from Rpgr knockout mouse, followed by immunoblotting validation Scientific reports Medium 26068394
2019 Both RPGR isoforms (RPGR1-19 and RPGRORF15) interact with endogenous PDE6D, INPP5E, and RPGRIP1L. RPGR1-19 contains two PDE6D binding sites, with the C-terminal prenylation site being the predominant one. Only RPGR1-19 localizes to cilia in RPE1 cells. Missense variants found in RPGR patients (including M58K) disrupt these interactions and abolish ciliary localization of RPGR1-19, establishing disruption of the RPGR protein interaction network as the common feature of pathogenic RPGR missense variants. Co-immunoprecipitation of endogenous proteins, ciliary localization assays in RPE1 cells, mutant analysis Proceedings of the National Academy of Sciences of the United States of America Medium 30622176
2019 In Rpgr conditional-knockout mouse retina, rhodopsin, cone opsins, and transducin are mislocalized in photoreceptors, and NPHP4 localization to connecting cilia is absent, demonstrating that RPGR is required for ciliary protein trafficking; microglia are activated prior to the onset of retinal degeneration. Conditional knockout mouse model, immunohistochemistry, immunofluorescence Journal of cellular physiology Medium 30924157
2022 Distal truncating variants in the RPGRORF15 C-terminal basic domain disrupt the interaction with TTLL5 and significantly impair RPGR glutamylation, leading to a cone-dominated (rather than rod-cone) dystrophy phenotype; the rod photoreceptor involvement diminishes as variant location approaches the distal ORF15 region. This mechanistically connects the C-terminal basic domain's role in TTLL5 recruitment to RPGR glutamylation and photoreceptor cell-type specificity of disease. Clinical cohort genotype-phenotype analysis, co-immunoprecipitation of RPGR variants with TTLL5, glutamylation assays Proceedings of the National Academy of Sciences of the United States of America Medium 36445968
2011 Overexpression of the constitutive Rpgr(ex1-19) isoform in transgenic mice causes atypical accumulation of RPGR in photoreceptor outer segments and severe retinal degeneration, worse than Rpgr knockout, establishing a dominant toxic gain-of-function effect for this isoform. The two RPGR isoforms exhibit variability in ciliary localization in adult photoreceptors, and are differentially regulated during retinal development. Transgenic mouse overexpression, immunoblot, immunofluorescence, protein fractionation, ERG, light/electron microscopy Investigative ophthalmology & visual science Medium 21546531
2004 Certain truncated forms of RPGR-ORF15 generated by photoreceptor-specific alternative splicing of a transgene cause more rapid photoreceptor degeneration than RPGR-null mutation, and act dominantly regardless of endogenous RPGR status, demonstrating that some RPGR truncation mutants are dominant gain-of-function alleles. Transgenic mouse (WT and RPGR-null background), RT-PCR, immunoblot, ERG, histology Investigative ophthalmology & visual science Medium 14691151

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nature genetics 426 8673101
2000 A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proceedings of the National Academy of Sciences of the United States of America 225 10725384
2002 A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. American journal of human genetics 216 11992260
2006 CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling. Nature 208 16778892
2002 Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Human molecular genetics 202 11978759
2003 RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. American journal of human genetics 197 14564670
2005 RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. The Journal of biological chemistry 144 16043481
2002 X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15. American journal of human genetics 144 11857109
2007 Disease course of patients with X-linked retinitis pigmentosa due to RPGR gene mutations. Investigative ophthalmology & visual science 135 17325176
2006 A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa. Investigative ophthalmology & visual science 121 16565408
2004 Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells. Experimental cell research 119 15265686
2012 Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 118 23351659
2007 RPGR mutation analysis and disease: an update. Human mutation 118 17195164
2002 Mutations in the RPGR gene cause X-linked cone dystrophy. Human molecular genetics 117 11875055
2015 RPGR: Its role in photoreceptor physiology, human disease, and future therapies. Experimental eye research 115 26093275
2000 Identification of a novel protein interacting with RPGR. Human molecular genetics 115 10958647
2002 X-linked recessive atrophic macular degeneration from RPGR mutation. Genomics 113 12160730
2012 Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Investigative ophthalmology & visual science 108 23150612
1997 Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro. Oncogene 96 9178888
2016 Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. Proceedings of the National Academy of Sciences of the United States of America 95 27162334
2017 Codon-Optimized RPGR Improves Stability and Efficacy of AAV8 Gene Therapy in Two Mouse Models of X-Linked Retinitis Pigmentosa. Molecular therapy : the journal of the American Society of Gene Therapy 93 28549772
2005 RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin. Human molecular genetics 92 15772089
1997 Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa. American journal of human genetics 89 9399904
2016 RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options. The British journal of ophthalmology 82 26843488
1997 Toll, a muscle cell surface molecule, locally inhibits synaptic initiation of the RP3 motoneuron growth cone in Drosophila. Development (Cambridge, England) 82 9108372
2002 Mutations of RPGR in X-linked retinitis pigmentosa (RP3). Human mutation 80 11968081
2005 The vacuolar DHHC-CRD protein Pfa3p is a protein acyltransferase for Vac8p. The Journal of cell biology 70 16186255
2017 Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations. Molecular therapy : the journal of the American Society of Gene Therapy 69 28566226
2005 A single, abbreviated RPGR-ORF15 variant reconstitutes RPGR function in vivo. Investigative ophthalmology & visual science 67 15671266
2018 Identification and Mapping of the Clubroot Resistance Gene CRd in Chinese Cabbage (Brassica rapa ssp. pekinensis). Frontiers in plant science 66 29868100
2015 Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa. Gene therapy 66 26348595
2002 Complex expression pattern of RPGR reveals a role for purine-rich exonic splicing enhancers. Investigative ophthalmology & visual science 65 12407146
2015 A long-term efficacy study of gene replacement therapy for RPGR-associated retinal degeneration. Human molecular genetics 64 25877300
2011 Gene therapeutic approach using mutation-adapted U1 snRNA to correct a RPGR splice defect in patient-derived cells. Molecular therapy : the journal of the American Society of Gene Therapy 63 21326217
2013 The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO reports 62 23559067
2007 CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a mammalian endoribonuclease. Nucleic acids research 60 17264115
2007 Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina: insights into X-linked Retinitis Pigmentosa and associated ciliopathies. Vision research 57 17904189
2004 Dominant, gain-of-function mutant produced by truncation of RPGR. Investigative ophthalmology & visual science 57 14691151
2023 Changes in Retinal Sensitivity Associated With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa With RPGR Gene Variations. JAMA ophthalmology 54 36757689
2011 The role of RPGR in cilia formation and actin stability. Human molecular genetics 53 21933838
2000 Remapping of the RP15 locus for X-linked cone-rod degeneration to Xp11.4-p21.1, and identification of a de novo insertion in the RPGR exon ORF15. American journal of human genetics 53 10970770
2002 Genetic and molecular characterization of the maize rp3 rust resistance locus. Genetics 50 12242248
2018 The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene. Investigative ophthalmology & visual science 49 30105367
2015 The Role of RPGR and Its Interacting Proteins in Ciliopathies. Journal of ophthalmology 49 26124960
1999 Difference between RP2 and RP3 phenotypes in X linked retinitis pigmentosa. The British journal of ophthalmology 49 10502575
2019 X-Chromosome Inactivation Is a Biomarker of Clinical Severity in Female Carriers of RPGR-Associated X-Linked Retinitis Pigmentosa. Ophthalmology. Retina 48 31953110
2015 Stability and Safety of an AAV Vector for Treating RPGR-ORF15 X-Linked Retinitis Pigmentosa. Human gene therapy 47 26076799
2007 Identification and characterization of a novel RPGR isoform in human retina. Human mutation 44 17405150
2018 Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling. Vascular pharmacology 42 29890296
2012 Ciliary transition zone (TZ) proteins RPGR and CEP290: role in photoreceptor cilia and degenerative diseases. Expert opinion on therapeutic targets 42 22563985
2010 Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions. Genes & cancer 39 21779431
2021 Restoration of RPGR expression in vivo using CRISPR/Cas9 gene editing. Gene therapy 37 34257417
2019 Disruption of RPGR protein interaction network is the common feature of RPGR missense variations that cause XLRP. Proceedings of the National Academy of Sciences of the United States of America 37 30622176
2016 Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. Human molecular genetics 37 26936822
2014 Role of CRD-BP in the growth of human basal cell carcinoma cells. The Journal of investigative dermatology 37 24468749
2013 Involvement of a pattern recognition receptor C-type lectin 7 in enhancing cellular encapsulation and melanization due to its carboxyl-terminal CRD domain in the cotton bollworm, Helicoverpa armigera. Developmental and comparative immunology 37 24269901
2019 Molecular Strategies for RPGR Gene Therapy. Genes 36 31487940
2010 RPGR: role in the photoreceptor cilium, human retinal disease, and gene therapy. Ophthalmic genetics 36 21174525
2007 A non-ancestral RPGR missense mutation in families with either recessive or semi-dominant X-linked retinitis pigmentosa. American journal of medical genetics. Part A 35 17480003
2022 Impaired glutamylation of RPGRORF15 underlies the cone-dominated phenotype associated with truncating distal ORF15 variants. Proceedings of the National Academy of Sciences of the United States of America 34 36445968
2000 Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). Human molecular genetics 33 10699176
2014 Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation. PloS one 32 24454928
1994 Clinical diversity and chromosomal localization of X-linked cone dystrophy (COD1). American journal of human genetics 32 7977377
2020 Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa. Investigative ophthalmology & visual science 31 32343782
2009 Mutation- and tissue-specific alterations of RPGR transcripts. Investigative ophthalmology & visual science 31 19834030
1999 Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa. European journal of human genetics : EJHG 31 10482958
2016 Disease mechanisms of X-linked retinitis pigmentosa due to RP2 and RPGR mutations. Biochemical Society transactions 30 27911705
2014 Function of two novel single-CRD containing C-type lectins in innate immunity from Eriocheir sinensis. Fish & shellfish immunology 30 24561128
2010 Multiprotein complexes of Retinitis Pigmentosa GTPase regulator (RPGR), a ciliary protein mutated in X-linked Retinitis Pigmentosa (XLRP). Advances in experimental medicine and biology 30 20238008
1999 The Drosophila SH2-SH3 adapter protein Dock is expressed in embryonic axons and facilitates synapse formation by the RP3 motoneuron. Development (Cambridge, England) 29 10068645
1993 From growth cone to synapse: the life history of the RP3 motor neuron. Development (Cambridge, England) 29 8049478
2024 Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa. American journal of ophthalmology 28 38871269
2003 CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression. Anticancer research 28 12894594
2021 TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction. Journal of cancer research and clinical oncology 27 33792796
2011 Misexpression of the constitutive Rpgr(ex1-19) variant leads to severe photoreceptor degeneration. Investigative ophthalmology & visual science 27 21546531
2015 Ablation of retinal ciliopathy protein RPGR results in altered photoreceptor ciliary composition. Scientific reports 26 26068394
2019 Disease mechanisms and neuroprotection by tauroursodeoxycholic acid in Rpgr knockout mice. Journal of cellular physiology 25 30924157
2009 RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction. Journal of genetics 25 20090203
1995 Identification of a novel gene, ETX1 from Xp21.1, a candidate gene for X-linked retintis pigmentosa (RP3). Human molecular genetics 24 8634709
2016 Loss of human disease protein retinitis pigmentosa GTPase regulator (RPGR) differentially affects rod or cone-enriched retina. Human molecular genetics 23 26908598
2013 The evolutionary analysis reveals domain fusion of proteins with Frizzled-like CRD domain. Gene 23 24135643
1996 Analysis of three deletion breakpoints in Xp21.1 and the further localization of RP3. Genomics 23 8921393
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2018 More Than Meets the Eye: Current Understanding of RPGR Function. Advances in experimental medicine and biology 21 29721984
2003 Phenotype in two families with RP3 associated with RPGR mutations. Ophthalmic genetics 21 12789573
1995 The actinophage RP3 DNA integrates site-specifically into the putative tRNA(Arg)(AGG) gene of Streptomyces rimosus. Nucleic acids research 21 7870591
1994 Modulation of the in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. III. Enhancement by RP-3 treatment of the anti-sheep red blood cell plaque-forming cell response in rats. Journal of immunology (Baltimore, Md. : 1950) 21 8027557
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2014 Gene augmentation for X-linked retinitis pigmentosa caused by mutations in RPGR. Cold Spring Harbor perspectives in medicine 20 25301933
2009 Phenotypic progression in X-linked retinitis pigmentosa secondary to a novel mutation in the RPGR gene. Eye (London, England) 20 19218993
2015 Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes. Animal genetics 19 25644216
2024 AAV-RPGR Gene Therapy Rescues Opsin Mislocalisation in a Human Retinal Organoid Model of RPGR-Associated X-Linked Retinitis Pigmentosa. International journal of molecular sciences 18 38339118
2022 Human iPSC-Derived Retinal Organoids and Retinal Pigment Epithelium for Novel Intronic RPGR Variant Assessment for Therapy Suitability. Journal of personalized medicine 18 35330501
2016 RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a prenylation- and PDE6D-dependent manner. Biology open 18 27493202
1998 Linkage analysis of X-linked cone-rod dystrophy: localization to Xp11.4 and definition of a locus distinct from RP2 and RP3. American journal of human genetics 18 9443860
2021 Clinical applications of microperimetry in RPGR-related retinitis pigmentosa: a review. Acta ophthalmologica 17 33783139
2018 Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. Human gene therapy. Clinical development 17 30280954
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