Affinage

RPGR

X-linked retinitis pigmentosa GTPase regulator · UniProt Q92834

Length
1020 aa
Mass
113.4 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPGR is a photoreceptor ciliary scaffold and guanine-nucleotide exchange factor that maintains polarized protein trafficking across the connecting cilium and whose loss causes progressive rod and cone degeneration in X-linked retinitis pigmentosa (RP3) (PMID:8673101, PMID:10725384). Its N-terminal RCC1-like propeller domain (RLD/RHD) serves as the principal protein-interaction module, mediating binding to PDEδ (PMID:9990021, PMID:23559067), to the anchoring protein RPGRIP1 (PMID:11104772, PMID:10958647, PMID:10958648), and to the small GTPase RAB8A, on which RPGR acts as a GEF to promote ciliary RAB8A localization and cilium formation (PMID:20631154). RPGR is tethered within the connecting cilium by RPGRIP1, which lies genetically upstream in the localization hierarchy, and is delivered to basal bodies via dynein-based retrograde transport in association with IFT88 and microtubule motors (PMID:12651948, PMID:16043481, PMID:19955120). Ciliary targeting depends on C-terminal prenylation enabling PDE6δ binding, which in turn is required for downstream ciliary trafficking of INPP5E (PMID:30622176, PMID:28172980), while CEP290 associates with RPGR and regulates its ciliary localization and that of phototransduction proteins (PMID:16632484, PMID:26936822). The photoreceptor-predominant ORF15 isoform, generated by ESE-mediated alternative splicing of a purine-rich repetitive region (PMID:12407146), is glutamylated within its Glu-Gly-rich domain specifically by TTLL5, which docks onto the C-terminal basic domain; loss of this modification reproduces the opsin-mislocalization and degeneration phenotype of RPGR-null retinas (PMID:27162334). RPGR loss disrupts polarized opsin transport and elevates RhoA-GTP and F-actin in rods (PMID:10725384, PMID:26908598), and the structural site of disruption determines disease character—basic-domain truncations that abolish TTLL5 binding and glutamylation shift the phenotype from rod-dominant to cone-dominant (PMID:36445968), while certain ORF15 truncations act as dominant gain-of-function alleles causing accelerated degeneration (PMID:14691151).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 Medium

    Establishing the gene responsible for RP3 and predicting from sequence that it is an RCC1-like GEF defined the foundational hypothesis that RPGR acts on a small GTPase.

    Evidence Positional cloning, genomic sequencing, and mutation analysis in RP3 patients with domain homology assessment

    PMID:8673101

    Open questions at the time
    • No biochemical reconstitution of GEF activity at this stage
    • Target GTPase unidentified
    • Subcellular localization not yet established
  2. 1999 High

    Identifying PDEδ as an RLD binding partner whose interaction is disrupted by RP3 mutations gave RPGR its first validated, disease-relevant molecular partner.

    Evidence Yeast two-hybrid, pull-down, surface plasmon resonance, and analysis of patient missense mutations

    PMID:9990021

    Open questions at the time
    • Functional consequence of PDEδ binding in vivo unresolved
    • Did not establish ciliary mechanism
  3. 2000 High

    Knockout mice and the discovery of the RPGRIP anchor located RPGR at the connecting cilium and showed it is required for polarized opsin distribution, defining its cell-biological role.

    Evidence Gene knockout mouse, immunofluorescence, ERG; yeast two-hybrid and Co-IP for RPGRIP interaction

    PMID:10725384 PMID:10958647 PMID:10958648 PMID:11104772

    Open questions at the time
    • Trafficking machinery linking RPGR to opsin transport not yet identified
    • Directionality of localization hierarchy not yet established
  4. 2002 High

    Mapping ESE-mediated alternative splicing of the purine-rich region explained the extreme isoform heterogeneity and identified the photoreceptor-specific ORF14/15 variant concentrated in the connecting cilium.

    Evidence RT-PCR, RACE, minigene expression constructs, immunoblot, immunocytochemistry

    PMID:12407146

    Open questions at the time
    • Functional distinction between isoforms not yet tested in vivo
    • Post-translational modification of ORF15 unknown
  5. 2003 High

    Double-knockout epistasis established RPGRIP as upstream of RPGR in ciliary tethering, and isoform-specific antibodies showed ORF15 versus default isoforms occupy distinct cilia, resolving the localization hierarchy.

    Evidence Double knockout mice, immunofluorescence, in vitro homodimerization, electron microscopy; isoform-specific antibodies across species

    PMID:12651948 PMID:12766038

    Open questions at the time
    • Mechanism by which RPGRIP recruits RPGR not biochemically defined
    • Functional role of distinct isoform localizations unresolved
  6. 2005 High

    Proteomic and rescue studies identified the trafficking machinery (IFT88, dynein/kinesin motors, NPM, SMC1/3) associated with ORF15 and showed ORF15 is the functionally critical photoreceptor isoform whose repeat length is dispensable.

    Evidence Mass spectrometry of retinal axoneme fraction, pull-downs, dynein-inhibition localization assays, and transgenic ORF15 rescue in KO mice

    PMID:15671266 PMID:15772089 PMID:16043481

    Open questions at the time
    • Functional significance of SMC1/3 and NPM associations unclear
    • Direct cargo of motor-associated transport not defined
  7. 2006 High

    Linking CEP290 to RPGR via Co-IP and a genetic mouse model placed RPGR within a broader connecting-cilium regulatory network controlling phototransduction protein distribution.

    Evidence Genetic mapping, immunogold, Co-IP, and immunofluorescence in rd16 mouse retina

    PMID:16632484

    Open questions at the time
    • Direct functional consequence of CEP290 binding on RPGR activity not defined
    • Interaction interface not mapped
  8. 2009 High

    Demonstrating RAB8A GEF activity finally validated the 1996 prediction, identifying the GTPase substrate and connecting RPGR to ciliary cargo trafficking and cilium length control.

    Evidence Co-IP, in vitro nucleotide exchange assay, siRNA knockdown in RPE1 cells with ciliary readouts; zebrafish morpholino with directional transport imaging and human rescue

    PMID:19955120 PMID:20631154

    Open questions at the time
    • Whether RAB8A GEF activity occurs at the connecting cilium in vivo not directly shown
    • Relationship between GEF activity and retrograde transport role unresolved
  9. 2011 Medium

    RPGR knockdown phenotypes extended its role beyond trafficking to cilia formation, cell-cycle progression, integrin-mediated attachment, and actin stress-fiber regulation.

    Evidence siRNA knockdown in RPE1 cells with attachment assays, signaling Western blots, and flow cytometry

    PMID:21933838

    Open questions at the time
    • Single-lab cell-line study; in vivo relevance to photoreceptors not established
    • Mechanism linking RPGR to actin/integrin signaling unknown
  10. 2013 High

    Crystal structures of the RLD propeller alone and bound to PDEδ provided a scaffold model in which RPGR recruits cargo-loaded PDEδ and exposes the Arl3-binding site to release lipidated cargo into cilia, and explained patient mutations structurally.

    Evidence X-ray crystallography of free domain and RPGR·PDEδ complex with biochemical binding assays

    PMID:23559067

    Open questions at the time
    • In vivo confirmation of cargo-release model in photoreceptors absent
    • Coordination of scaffold and GEF functions unresolved
  11. 2016 High

    Identification of TTLL5 as the specific glutamylase of ORF15, together with prenylation-dependent PDE6δ/INPP5E/CEP290 trafficking findings, defined the post-translational and targeting determinants of RPGR ciliary function.

    Evidence In vitro glutamylation assays, Co-IP, Ttll5 and Cep290/Rpgr mouse models, domain-mapping pull-downs, and ciliary localization assays

    PMID:26908598 PMID:26936822 PMID:27162334 PMID:28172980 PMID:30622176

    Open questions at the time
    • Molecular consequence of glutamylation on RPGR activity not fully defined
    • How distinct rod (actin) versus cone (visual cycle) pathways diverge mechanistically unresolved
  12. 2022 High

    Genotype-phenotype analysis tied disruption of the TTLL5-binding basic domain and consequent loss of glutamylation to a switch from rod-dominant to cone-dominant dystrophy, mechanistically linking a specific structural perturbation to disease subtype.

    Evidence Clinical cohort of 116 patients with biochemical TTLL5-RPGR interaction and glutamylation assays on truncating mutants

    PMID:36445968

    Open questions at the time
    • Why glutamylation loss preferentially affects cones not mechanistically explained
    • Therapeutic implications of restoring glutamylation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RPGR's scaffold (PDEδ/Arl3 cargo release), GEF (RAB8A), and ORF15 glutamylation functions are coordinated in vivo to maintain photoreceptor-type-specific homeostasis.
  • Integration of scaffold versus GEF activities unknown
  • Mechanistic basis of rod versus cone vulnerability incomplete
  • Spatiotemporal regulation of glutamylation in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005929 cilium 4 GO:0005815 microtubule organizing center 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-9609507 Protein localization 2 R-HSA-9709957 Sensory Perception 2
Partners
CEP290IFT88INPP5ENPM1PDE6DRAB8ARPGRIP1TTLL5

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RPGR encodes a predicted 90 kDa protein with an N-terminal tandem repeat domain highly homologous to RCC1 (regulator of chromosome condensation), a guanine nucleotide exchange factor, suggesting interaction with a small GTPase. The C-terminal half contains an acidic domain and a potential isoprenylation anchorage site. Intragenic deletions, nonsense, and missense mutations within conserved domains were identified in RP3 patients. Positional cloning, genomic sequencing, mutation analysis, sequence homology Nature genetics Medium 8673101
1999 RPGR interacts with the delta subunit of rod cyclic GMP phosphodiesterase (PDEdelta) via its RCC1-like domain (RLD). The binding affinity is ~90 nM. Six RP3-associated missense mutations in the RLD all showed reduced interaction with PDEdelta, while a non-RP3 missense outside the RLD did not abolish the interaction. Yeast two-hybrid screen, pull-down assay, surface plasmon resonance, two-hybrid analysis of patient mutations Proceedings of the National Academy of Sciences of the United States of America High 9990021
2000 RPGR is normally localized to the connecting cilia of rod and cone photoreceptors. In RPGR-deficient (knockout) mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses, and rod photoreceptors have reduced rhodopsin, followed by degeneration of both rod and cone photoreceptors. This indicates RPGR is required for maintaining polarized protein distribution across the connecting cilium. Gene knockout mouse model, immunofluorescence, electroretinography, histology Proceedings of the National Academy of Sciences of the United States of America High 10725384
2000 RPGRIP (RPGR-interacting protein) was identified as a direct binding partner of RPGR via yeast two-hybrid screening. RPGRIP is expressed specifically in rod and cone photoreceptors, contains coiled-coil domains, and co-localizes with RPGR in the photoreceptor connecting cilia. RPGRIP is stably associated with the ciliary axoneme and functions to anchor RPGR within the cilium. Yeast two-hybrid, co-immunoprecipitation of in vitro translated proteins, immunolocalization in retina, protein fractionation The Journal of biological chemistry High 10958647 11104772
2000 RPGR interacts with RPGRIP1 isoforms via the RCC1-homologous domain (RHD). RP3-associated missense mutations in RPGR impaired the in vivo interaction with RPGRIP1. RPGR and RPGRIP1 co-localize in the outer segment of rod photoreceptors. RPGRIP1 isoforms contain stretches homologous to proteins involved in vesicular trafficking. Yeast two-hybrid library screen, in vivo and in vitro interaction assays, immunolocalization, mutation analysis Human molecular genetics High 10958648
2003 RPGR is absent from the connecting cilium of photoreceptors lacking RPGRIP, but RPGRIP is present in photoreceptors lacking RPGR, establishing RPGRIP as upstream of RPGR in the ciliary localization pathway (RPGRIP tethers RPGR). RPGRIP forms homodimers and elongated filaments via coiled-coil and C-terminal domain interactions in vitro. Double knockout mouse models, immunofluorescence, in vitro protein interaction (homodimerization), electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 12651948
2003 RPGR ORF15 isoform localizes to the photoreceptor connecting cilia, while the constitutive RPGR (default) isoform localizes to the transitional zone of motile cilia in airway epithelia. RPGR ORF15 is the predominant variant in photoreceptor connecting cilia. Isoform-specific antibodies, immunofluorescence in multiple mammalian species, immunoblot analysis of serial photoreceptor cross-sections Investigative ophthalmology & visual science High 12766038
2002 RPGR transcripts are exceptionally heterogeneous due to alternative RNA splicing mediated by multiple exonic splicing enhancers (ESEs) in the purine-rich region, which interact with SR proteins. RPGR produces a population of proteins with a constant N-terminal RCC1 homology domain and a C-terminal portion of variable lengths. ORF14/15-encoded RPGR polypeptides (~200 kDa) are photoreceptor-specific and concentrate in the connecting cilium. RT-PCR, RACE, minigene transient expression constructs, immunoblot, immunocytochemistry Investigative ophthalmology & visual science High 12407146
2005 RPGR ORF15 isoform localizes to the basal bodies of photoreceptor connecting cilium and to the tip and axoneme of sperm flagella. RPGR-ORF15 associates with structural maintenance of chromosomes proteins SMC1 and SMC3 (interaction mediated at least in part by the RCC1-like domain) and with intraflagellar transport protein IFT88, and microtubule motors KIF3A, p150Glued, and p50-dynamitin. Inhibition of dynein by overexpressing p50-dynamitin abrogated RPGR-ORF15 localization to basal bodies. Mass spectrometry of immunoprecipitated retinal axoneme fraction, pull-down assays, immunoprecipitation, immunofluorescence, dynein inhibition experiments The Journal of biological chemistry High 16043481
2005 RPGR ORF15 and RPGRIP1 co-localize at centrioles (nocodazole-resistant) and basal bodies throughout the cell cycle in cultured mammalian cells. The C-terminal C2 domain of RPGR ORF15 interacts with nucleophosmin (NPM), a multifunctional chaperone associated with centrosomal division, as validated by mass spectrometry, yeast two-hybrid, in vitro binding, co-immunoprecipitation from bovine retinal extracts and cultured cells, and co-localization at metaphase centrosomes. MALDI-TOF MS, yeast two-hybrid, in vitro binding with recombinant and native NPM, co-immunoprecipitation from bovine retina and HeLa cells, immunofluorescence Human molecular genetics High 15772089
2005 An abbreviated RPGR-ORF15 transgene (lacking 654 bp of the repetitive region) localizes to connecting cilia at ~20% of wild-type levels and substantially rescues retinal degeneration in RPGR knockout mice, demonstrating that ORF15 is the functionally significant variant in photoreceptors and that the precise length of its repetitive region is not critical for function. Transgenic mouse rescue experiment, immunofluorescence, electroretinography, light and electron microscopy Investigative ophthalmology & visual science High 15671266
2006 CEP290 associates with RPGR in the photoreceptor connecting cilium. In rd16 mice carrying a truncated CEP290, RPGR and phototransduction proteins are redistributed in photoreceptors. The truncated CEP290 protein exhibits stronger association with specific RPGR isoforms, suggesting CEP290 normally regulates RPGR localization and ciliary transport. Genetic mapping, immunogold labeling, co-immunoprecipitation, immunofluorescence in mouse retina Human molecular genetics High 16632484
2009 RPGR interacts with the small GTPase RAB8A, primarily associating with the GDP-bound form, and stimulates GDP/GTP nucleotide exchange on RAB8A (GEF activity). Disease-causing RPGR mutations diminish interaction with RAB8A and reduce GEF activity. Depletion of RPGR in hTERT-RPE1 cells interferes with ciliary localization of RAB8A and results in shorter primary cilia. Co-immunoprecipitation, nucleotide exchange assay (GEF activity), siRNA knockdown in RPE1 cells, immunofluorescence Human molecular genetics High 20631154
2011 RPGR knockdown in hTERT-RPE1 cells results in reduced cilia number, slower cell cycle progression, impaired fibronectin attachment (but no migration defect), and stronger actin stress filaments associated with dysregulation of Akt, Erk1/2, FAK, and Src signaling pathways and reduced surface β1-integrin. This reveals a novel function for RPGR in cilia formation and regulation of actin stress filaments. siRNA knockdown, immunofluorescence, cell attachment assay, wound-healing assay, Western blot signaling analysis, flow cytometry for surface integrins Human molecular genetics Medium 21933838
2013 The crystal structure of the RPGR RCC1-like propeller domain reveals the location of patient mutations and how they perturb the structure. The RPGR·PDEdelta complex structure shows PDEdelta binding on a highly conserved surface patch of RPGR. Biochemical experiments show RPGR can bind with high affinity to cargo-loaded PDEdelta and exposes the Arl2/Arl3-binding site on PDEdelta, supporting a scaffold model in which RPGR recruits cargo-loaded PDEdelta and Arl3 to release lipidated cargo into cilia. X-ray crystallography (RPGR propeller domain alone and in complex with PDEdelta), 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 to the noncatalytic cofactor interaction domain of TTLL5, targeting TTLL5 to glutamylate RPGR. Only TTLL5 (not other TTLL family glutamylases) interacts with RPGR ORF15 in cells. Ttll5 mutant mice show complete loss of RPGR glutamylation without marked changes in tubulin glutamylation, and develop slow photoreceptor degeneration with cone opsin mislocalization resembling Rpgr-null mice. In vitro glutamylation assay, co-immunoprecipitation of TTLL5 and RPGR, Ttll5 knockout mouse analysis, isoform-specific antibodies, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 27162334
2016 RPGR (RPGR1-19 isoform) interacts with endogenous PDE6D, INPP5E, and RPGRIP1L. The C-terminal prenylation site of RPGR1-19 is the predominant PDE6D binding site and regulates interactions with INPP5E and RPGRIP1L. Only the RPGR1-19 isoform (not RPGRORF15) localizes to cilia in cultured RPE1 cells. Disease-causing missense mutations in RPGR disrupt interactions with these endogenous interactors, and M58K also disrupts ciliary localization of RPGR1-19. Co-immunoprecipitation with endogenous proteins, ciliary localization assay in RPE1 cells, missense mutation analysis Proceedings of the National Academy of Sciences of the United States of America High 30622176
2016 PDE6δ binds selectively to the C-terminus of RPGR and this interaction is critical for RPGR's localization to cilia. INPP5E associates with the N-terminus of RPGR, and trafficking of INPP5E to cilia is dependent on the ciliary localization of RPGR. Thus RPGR prenylation (enabling PDE6δ interaction) is required for RPGR ciliary targeting, which in turn is required for INPP5E ciliary trafficking. Proteomic and biochemical interaction assays, domain mapping pull-downs, immunofluorescence in ciliated cells with RPGR knockdown Human molecular genetics High 28172980
2016 Rpgr knockout mice with a heterozygous hypomorphic allele of Cep290 (Cep290rd16/+) exhibit earlier onset retinal degeneration (by 3 months vs ~7 months in Rpgr KO alone), disorganized outer-segment morphology, and defective opsin trafficking, demonstrating genetic interaction between RPGR and CEP290. This interaction is supported by a physical interaction between RPGR and the C-terminal domain of CEP290. Double-mutant mouse genetic epistasis, co-immunoprecipitation (RPGR and CEP290 C-terminal domain), ERG, histology, immunofluorescence Human molecular genetics High 26936822
2007 RPGR isoforms (RPGR 1-19 and RPGR ORF15) localize to distinct subcellular compartments in mammalian photoreceptors, associate with cilia-centrosomal proteins, and the RCC1-like domain of RPGR is sufficient to target it to cilia and centrosomes in cultured cells. Isoform-specific antibodies, sucrose-gradient centrifugation, immunofluorescence, co-immunoprecipitation, transfection of truncated constructs in cultured cells Vision research Medium 17904189
2004 Certain truncated RPGR ORF15 alleles (generated by alternative splicing of the purine-rich region creating a premature stop) act as dominant gain-of-function mutants, causing more rapid photoreceptor degeneration than RPGR null mutations. The disease course was similar whether the truncated transgene was coexpressed with wild-type RPGR or expressed alone in the RPGR null background. Transgenic mouse experiment (dominant gain-of-function in WT and KO backgrounds), RT-PCR, immunoblot, immunofluorescence, ERG, histology Investigative ophthalmology & visual science High 14691151
2009 Zebrafish RPGR2 (functionally orthologous to human RPGR) is required for normal retinal development and differentiation. RPGR knockdown causes retrograde but not anterograde intracellular organelle transport defects, consistent with a role in dynein-based retrograde transport. Human wild-type RPGR (but not disease-causing mutants) rescues zebrafish RPGR knockdown developmental defects. Morpholino knockdown in zebrafish, live imaging of organelle transport (retrograde vs anterograde), rescue with human RPGR WT and disease mutants, histology, TUNEL Human molecular genetics High 19955120
2015 Loss of RPGR in a rod-dominant Rpgr knockout mouse results in predominant upregulation of actin cytoskeletal dynamics genes and increased activated RhoA-GTP and polymerized F-actin before onset of degeneration. In cone-dominant Rpgr KO::Nrl-/- double knockout mice, supranormal cone light responses and upregulation of RPE-specific visual cycle genes were observed instead, revealing distinct intracellular pathways (actin in rods, visual cycle in cones) disrupted by RPGR loss. Transcriptomic analysis, RhoA-GTP activation assay, F-actin staining, ERG, double knockout mouse model (Rpgr KO × Nrl KO), fatty acid analysis Human molecular genetics Medium 26908598
2022 Truncating RPGR ORF15 variants located in the distal part of ORF15 (including the C-terminal basic domain) disrupt interaction with TTLL5 and lead to significant impairment of RPGR glutamylation, resulting in a cone-dominated rather than rod-dominated retinal dystrophy phenotype. This links RPGR glutamylation status (via TTLL5 interaction through the basic domain) to the specific photoreceptor type primarily affected. Clinical cohort genotype-phenotype analysis (116 patients), biochemical interaction assays (TTLL5-RPGR interaction with truncating mutants), glutamylation assays Proceedings of the National Academy of Sciences of the United States of America High 36445968

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 427 8673101
2000 Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nature genetics 392 10932196
2006 In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Human molecular genetics 313 16632484
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 227 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 217 11992260
2002 Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Human molecular genetics 203 11978759
2003 RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. American journal of human genetics 197 14564670
2003 RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Investigative ophthalmology & visual science 190 12766038
2003 The retinitis pigmentosa GTPase regulator (RPGR)- interacting protein: subserving RPGR function and participating in disk morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 186 12651948
2000 Retinitis pigmentosa GTPase regulator (RPGRr)-interacting protein is stably associated with the photoreceptor ciliary axoneme and anchors RPGR to the connecting cilium. The Journal of biological chemistry 175 11104772
2000 The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors. Human molecular genetics 173 10958648
2005 RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1, SMC3, and microtubule transport proteins. The Journal of biological chemistry 144 16043481
2007 Disease course of patients with X-linked retinitis pigmentosa due to RPGR gene mutations. Investigative ophthalmology & visual science 136 17325176
2001 Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis. European journal of human genetics : EJHG 133 11528500
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 122 16565408
2007 RPGR mutation analysis and disease: an update. Human mutation 119 17195164
2012 Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 118 23351659
2015 RPGR: Its role in photoreceptor physiology, human disease, and future therapies. Experimental eye research 117 26093275
2002 Mutations in the RPGR gene cause X-linked cone dystrophy. Human molecular genetics 117 11875055
1999 The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Proceedings of the National Academy of Sciences of the United States of America 116 9990021
2007 Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling. Human mutation 115 16969763
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 109 23150612
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 98 27162334
2000 X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function. Investigative ophthalmology & visual science 95 10937588
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
2010 Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration. Human molecular genetics 93 20631154
2005 RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin. Human molecular genetics 93 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 90 9399904
1997 Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Investigative ophthalmology & visual science 84 9331262
2016 RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options. The British journal of ophthalmology 82 26843488
2002 Mutations of RPGR in X-linked retinitis pigmentosa (RP3). Human mutation 80 11968081
2019 CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study. Retina (Philadelphia, Pa.) 77 29528978
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 71 28566226
2012 RPGR mutations might cause reduced orientation of respiratory cilia. Pediatric pulmonology 69 22888088
2005 A single, abbreviated RPGR-ORF15 variant reconstitutes RPGR function in vivo. Investigative ophthalmology & visual science 69 15671266
2007 Functional correlates of fundus autofluorescence abnormalities in patients with RPGR or RIMS1 mutations causing cone or cone rod dystrophy. The British journal of ophthalmology 68 17962389
2015 Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa. Gene therapy 67 26348595
2003 Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families. American journal of ophthalmology 65 14516808
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
2013 The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO reports 64 23559067
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
2012 RPGR-associated retinal degeneration in human X-linked RP and a murine model. Investigative ophthalmology & visual science 59 22807293
1997 Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: paucity of mutations in the coding region but splice defects in two families. American journal of human genetics 59 9326322
2007 Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina: insights into X-linked Retinitis Pigmentosa and associated ciliopathies. Vision research 58 17904189
2023 Changes in Retinal Sensitivity Associated With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa With RPGR Gene Variations. JAMA ophthalmology 57 36757689
2004 Dominant, gain-of-function mutant produced by truncation of RPGR. Investigative ophthalmology & visual science 57 14691151
2011 The role of RPGR in cilia formation and actin stability. Human molecular genetics 54 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 54 10970770
2015 The Role of RPGR and Its Interacting Proteins in Ciliopathies. Journal of ophthalmology 50 26124960
2019 X-Chromosome Inactivation Is a Biomarker of Clinical Severity in Female Carriers of RPGR-Associated X-Linked Retinitis Pigmentosa. Ophthalmology. Retina 49 31953110
2018 The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene. Investigative ophthalmology & visual science 49 30105367
2009 Zebrafish Rpgr is required for normal retinal development and plays a role in dynein-based retrograde transport processes. Human molecular genetics 49 19955120
2015 Stability and Safety of an AAV Vector for Treating RPGR-ORF15 X-Linked Retinitis Pigmentosa. Human gene therapy 48 26076799
2008 Discordant phenotypes in fraternal twins having an identical mutation in exon ORF15 of the RPGR gene. Archives of ophthalmology (Chicago, Ill. : 1960) 48 18332319
2007 Identification and characterization of a novel RPGR isoform in human retina. Human mutation 45 17405150
2012 Ciliary transition zone (TZ) proteins RPGR and CEP290: role in photoreceptor cilia and degenerative diseases. Expert opinion on therapeutic targets 42 22563985
2011 Clinical course of cone dystrophy caused by mutations in the RPGR gene. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 41 21866333
1999 Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3). Human mutation 40 10094550
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 39 30622176
2021 Restoration of RPGR expression in vivo using CRISPR/Cas9 gene editing. Gene therapy 38 34257417
2002 Retinal histopathology of an XLRP carrier with a mutation in the RPGR exon ORF15. Experimental eye research 38 12387791
2016 Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR. Human molecular genetics 37 26936822
2016 Prenylated retinal ciliopathy protein RPGR interacts with PDE6δ and regulates ciliary localization of Joubert syndrome-associated protein INPP5E. Human molecular genetics 37 28172980
2009 Cone versus rod disease in a mutant Rpgr mouse caused by different genetic backgrounds. Investigative ophthalmology & visual science 37 20007830
2006 Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: identification of four mutations. Molecular vision 37 17093403
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 36 36445968
2020 Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized RPGR Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa. Human gene therapy 36 31910043
2019 Molecular Strategies for RPGR Gene Therapy. Genes 36 31487940
2018 Characterization of Visual Function, Interocular Variability and Progression Using Static Perimetry-Derived Metrics in RPGR-Associated Retinopathy. Investigative ophthalmology & visual science 36 29847648
2010 RPGR: role in the photoreceptor cilium, human retinal disease, and gene therapy. Ophthalmic genetics 36 21174525
2018 QUANTITATIVE ANALYSIS OF HYPERAUTOFLUORESCENT RINGS TO CHARACTERIZE THE NATURAL HISTORY AND PROGRESSION IN RPGR-ASSOCIATED RETINOPATHY. Retina (Philadelphia, Pa.) 35 29016458
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
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 34 38871269
2001 Three novel mutations of the RPGR gene exon ORF15 in three Japanese families with X-linked retinitis pigmentosa. American journal of medical genetics 34 11754050
2016 Variegated yet non-random rod and cone photoreceptor disease patterns in RPGR-ORF15-associated retinal degeneration. Human molecular genetics 32 27798110
2014 Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation. PloS one 32 24454928
2020 Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa. Investigative ophthalmology & visual science 31 32343782
2016 Disease mechanisms of X-linked retinitis pigmentosa due to RP2 and RPGR mutations. Biochemical Society transactions 31 27911705
2009 Mutation- and tissue-specific alterations of RPGR transcripts. Investigative ophthalmology & visual science 31 19834030
2006 Rod and cone opsin mislocalization in an autopsy eye from a carrier of X-linked retinitis pigmentosa with a Gly436Asp mutation in the RPGR gene. American journal of ophthalmology 31 16935610
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
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
2011 Misexpression of the constitutive Rpgr(ex1-19) variant leads to severe photoreceptor degeneration. Investigative ophthalmology & visual science 28 21546531
2017 High Symmetry of Visual Acuity and Visual Fields in RPGR-Linked Retinitis Pigmentosa. Investigative ophthalmology & visual science 27 28863407
2020 Dose Range Finding Studies with Two RPGR Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy. Human gene therapy 26 32414297
2018 Development of High-Throughput Clinical Testing of RPGR ORF15 Using a Large Inherited Retinal Dystrophy Cohort. Investigative ophthalmology & visual science 26 30193314
2015 Ablation of retinal ciliopathy protein RPGR results in altered photoreceptor ciliary composition. Scientific reports 26 26068394
2009 RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population. The British journal of ophthalmology 26 19429592
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
2016 Loss of human disease protein retinitis pigmentosa GTPase regulator (RPGR) differentially affects rod or cone-enriched retina. Human molecular genetics 24 26908598
2018 More Than Meets the Eye: Current Understanding of RPGR Function. Advances in experimental medicine and biology 23 29721984
2014 Gene augmentation for X-linked retinitis pigmentosa caused by mutations in RPGR. Cold Spring Harbor perspectives in medicine 22 25301933
2022 Emerging gene therapy products for RPGR-associated X-linked retinitis pigmentosa. Expert opinion on emerging drugs 21 36562395
2019 Development of a Molecularly Stable Gene Therapy Vector for the Treatment of RPGR-Associated X-Linked Retinitis Pigmentosa. Human gene therapy 21 31106594
2006 A novel RPGR exon ORF15 mutation in a family with X-linked retinitis pigmentosa and Coats'-like exudative vasculopathy. American journal of ophthalmology 21 16387007
2003 Phenotype in two families with RP3 associated with RPGR mutations. Ophthalmic genetics 21 12789573

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