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Gene Review

RPGR  -  retinitis pigmentosa GTPase regulator

Homo sapiens

Synonyms: COD1, CORDX1, CRD, PCDX, RP15, ...
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Disease relevance of RPGR


Psychiatry related information on RPGR


High impact information on RPGR

  • Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin [8].
  • Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa [9].
  • Because the mutations in the remainder of the XLRP patients may reside in undiscovered exons of RPGR, we sequenced a 172-kb region containing the entire gene [9].
  • The gene RPGR was previously identified in the RP3 region of Xp21.1 and shown to be mutated in 10-20% of patients with the progressive retinal degeneration X-linked retinitis pigmentosa (XLRP) [9].
  • The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval [10].

Chemical compound and disease context of RPGR


Biological context of RPGR

  • The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene [14].
  • 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 [15].
  • Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase) [16].
  • Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations [1].
  • However, mouse models null for RPGR had, surprisingly, a very mild phenotype compared with those observed in XlRP3-affected humans and dogs [17].

Anatomical context of RPGR

  • We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells [8].
  • Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors [18].
  • Consistent with expression of RPGR in rods and cones, our results show that mutations in RPGR, in addition to X-linked RP, can also cause cone-specific degeneration [19].
  • These data suggest that RPGRIP is a structural component of the ciliary axoneme, and one of its functions is to anchor RPGR within the cilium [20].
  • Leukocyte genomic DNA samples were obtained and screened for RPGR (RP3) mutations by direct polymerase chain reaction sequencing [21].

Associations of RPGR with chemical compounds

  • In a yeast two-hybrid screen we identified the delta subunit of rod cyclic GMP phosphodiesterase (PDEdelta) as interacting with the RCC1-like domain (RLD) of RPGR (RPGR392) [2].
  • Complex expression pattern of RPGR reveals a role for purine-rich exonic splicing enhancers [22].
  • Sequence analysis of the RPGR gene identified a single base pair change, a G-->T transversion, that converts codon 52 GGA (Gly) to TGA (stop codon); the mutation segregates with the disease [23].
  • CONCLUSIONS: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females [11].
  • In contrast, the much narrower binding specificity of selectin cell adhesion molecules results from an extended binding site within a single CRD [24].

Physical interactions of RPGR


Other interactions of RPGR

  • The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus [27].
  • RESULTS: Screening of 58 xlRP families revealed RP2 mutations in 8% and RPGR mutations in 71% of families with definite X-linked inheritance [28].
  • Six of these mutations were detected in the conserved amino-terminal region of RPGR protein, containing tandem repeats homologous to the RCC1 protein, a guanine nucleotide-exchange factor for Ran-GTPase [29].
  • Because mutations in the RPGR gene to date account for disease in only a small proportion of RP3 families, the possibility that this new locus (CSNB4) also segregates with an as yet unidentified XLRP locus cannot be excluded [30].
  • X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15 [28].

Analytical, diagnostic and therapeutic context of RPGR

  • The specificity of the interaction was confirmed by co-immunoprecipitation of in vitro translated protein and using RPGR mutants [31].
  • PCR amplification and Southern blot analysis revealed the absence of the 5' half of the RPGR gene [32].
  • Reverse transcription-polymerase chain reaction (RT-PCR) was performed by using the primers flanking exon 2 of RPGR transcript, followed by gel purification and direct sequencing [33].
  • Comparative northern blot hybridization of ubiquitous and tissue-specific RPGR probes identified high molecular weight transcripts with similar expression patterns in both human and mouse [34].
  • Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies [35].


  1. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Sharon, D., Sandberg, M.A., Rabe, V.W., Stillberger, M., Dryja, T.P., Berson, E.L. Am. J. Hum. Genet. (2003) [Pubmed]
  2. The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase. Linari, M., Ueffing, M., Manson, F., Wright, A., Meitinger, T., Becker, J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes. Andréasson, S., Breuer, D.K., Eksandh, L., Ponjavic, V., Frennesson, C., Hiriyanna, S., Filippova, E., Yashar, B.M., Swaroop, A. Ophthalmic Genet. (2003) [Pubmed]
  4. Fine mapping of canine XLPRA establishes homology of the human and canine RP3 intervals. Zhang, Q., Acland, G.M., Zangerl, B., Johnson, J.L., Mao, Z., Zeiss, C.J., Ostrander, E.A., Aguirre, G.D. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  5. Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Sullivan, L.S., Bowne, S.J., Birch, D.G., Hughbanks-Wheaton, D., Heckenlively, J.R., Lewis, R.A., Garcia, C.A., Ruiz, R.S., Blanton, S.H., Northrup, H., Gire, A.I., Seaman, R., Duzkale, H., Spellicy, C.J., Zhu, J., Shankar, S.P., Daiger, S.P. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  6. A recombination outside the BB deletion refines the location of the X linked retinitis pigmentosa locus RP3. Fujita, R., Bingham, E., Forsythe, P., McHenry, C., Aita, V., Navia, B.A., Dry, K., Segal, M., Devoto, M., Bruns, G., Wright, A.F., Ott, J., Sieving, P.A., Swaroop, A. Am. J. Hum. Genet. (1996) [Pubmed]
  7. A new clinical scale for the staging of dementia. Hughes, C.P., Berg, L., Danziger, W.L., Coben, L.A., Martin, R.L. The British journal of psychiatry : the journal of mental science. (1982) [Pubmed]
  8. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Otto, E.A., Loeys, B., Khanna, H., Hellemans, J., Sudbrak, R., Fan, S., Muerb, U., O'Toole, J.F., Helou, J., Attanasio, M., Utsch, B., Sayer, J.A., Lillo, C., Jimeno, D., Coucke, P., De Paepe, A., Reinhardt, R., Klages, S., Tsuda, M., Kawakami, I., Kusakabe, T., Omran, H., Imm, A., Tippens, M., Raymond, P.A., Hill, J., Beales, P., He, S., Kispert, A., Margolis, B., Williams, D.S., Swaroop, A., Hildebrandt, F. Nat. Genet. (2005) [Pubmed]
  9. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Vervoort, R., Lennon, A., Bird, A.C., Tulloch, B., Axton, R., Miano, M.G., Meindl, A., Meitinger, T., Ciccodicola, A., Wright, A.F. Nat. Genet. (2000) [Pubmed]
  10. Positional cloning of the gene for X-linked retinitis pigmentosa 2. Schwahn, U., Lenzner, S., Dong, J., Feil, S., Hinzmann, B., van Duijnhoven, G., Kirschner, R., Hemberger, M., Bergen, A.A., Rosenberg, T., Pinckers, A.J., Fundele, R., Rosenthal, A., Cremers, F.P., Ropers, H.H., Berger, W. Nat. Genet. (1998) [Pubmed]
  11. X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60. Fishman, G.A., Grover, S., Jacobson, S.G., Alexander, K.R., Derlacki, D.J., Wu, W., Buraczynska, M., Swaroop, A. Ophthalmology (1998) [Pubmed]
  12. RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia. Hong, D.H., Pawlyk, B., Sokolov, M., Strissel, K.J., Yang, J., Tulloch, B., Wright, A.F., Arshavsky, V.Y., Li, T. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  13. Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Velidedeoglu, E., Bloom, R.D., Crawford, M.D., Desai, N.M., Campos, L., Abt, P.L., Markmann, J.W., Mange, K.C., Olthoff, K.M., Shaked, A., Markmann, J.F. Transplantation (2004) [Pubmed]
  14. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Meindl, A., Dry, K., Herrmann, K., Manson, F., Ciccodicola, A., Edgar, A., Carvalho, M.R., Achatz, H., Hellebrand, H., Lennon, A., Migliaccio, C., Porter, K., Zrenner, E., Bird, A., Jay, M., Lorenz, B., Wittwer, B., D'Urso, M., Meitinger, T., Wright, A. Nat. Genet. (1996) [Pubmed]
  15. 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. Fujita, R., Buraczynska, M., Gieser, L., Wu, W., Forsythe, P., Abrahamson, M., Jacobson, S.G., Sieving, P.A., Andréasson, S., Swaroop, A. Am. J. Hum. Genet. (1997) [Pubmed]
  16. Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa. Buraczynska, M., Wu, W., Fujita, R., Buraczynska, K., Phelps, E., Andréasson, S., Bennett, J., Birch, D.G., Fishman, G.A., Hoffman, D.R., Inana, G., Jacobson, S.G., Musarella, M.A., Sieving, P.A., Swaroop, A. Am. J. Hum. Genet. (1997) [Pubmed]
  17. Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species. Mavlyutov, T.A., Zhao, H., Ferreira, P.A. Hum. Mol. Genet. (2002) [Pubmed]
  18. Null RPGRIP1 alleles in patients with Leber congenital amaurosis. Dryja, T.P., Adams, S.M., Grimsby, J.L., McGee, T.L., Hong, D.H., Li, T., Andréasson, S., Berson, E.L. Am. J. Hum. Genet. (2001) [Pubmed]
  19. Mutations in the RPGR gene cause X-linked cone dystrophy. Yang, Z., Peachey, N.S., Moshfeghi, D.M., Thirumalaichary, S., Chorich, L., Shugart, Y.Y., Fan, K., Zhang, K. Hum. Mol. Genet. (2002) [Pubmed]
  20. Retinitis pigmentosa GTPase regulator (RPGRr)-interacting protein is stably associated with the photoreceptor ciliary axoneme and anchors RPGR to the connecting cilium. Hong, D.H., Yue, G., Adamian, M., Li, T. J. Biol. Chem. (2001) [Pubmed]
  21. A novel RPGR exon ORF15 mutation in a family with X-linked retinitis pigmentosa and Coats'-like exudative vasculopathy. Demirci, F.Y., Rigatti, B.W., Mah, T.S., Gorin, M.B. Am. J. Ophthalmol. (2006) [Pubmed]
  22. Complex expression pattern of RPGR reveals a role for purine-rich exonic splicing enhancers. Hong, D.H., Li, T. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  23. Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Jacobson, S.G., Buraczynska, M., Milam, A.H., Chen, C., Järvaläinen, M., Fujita, R., Wu, W., Huang, Y., Cideciyan, A.V., Swaroop, A. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  24. The C-type lectin superfamily in the immune system. Weis, W.I., Taylor, M.E., Drickamer, K. Immunol. Rev. (1998) [Pubmed]
  25. Insights into X-linked retinitis pigmentosa type 3, allied diseases and underlying pathomechanisms. Ferreira, P.A. Hum. Mol. Genet. (2005) [Pubmed]
  26. RPGRIP1 is mutated in Leber congenital amaurosis: a mini-review. Koenekoop, R.K. Ophthalmic Genet. (2005) [Pubmed]
  27. Linkage analysis of X-linked cone-rod dystrophy: localization to Xp11.4 and definition of a locus distinct from RP2 and RP3. Seymour, A.B., Dash-Modi, A., O'Connell, J.R., Shaffer-Gordon, M., Mah, T.S., Stefko, S.T., Nagaraja, R., Brown, J., Kimura, A.E., Ferrell, R.E., Gorin, M.B. Am. J. Hum. Genet. (1998) [Pubmed]
  28. X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15. Bader, I., Brandau, O., Achatz, H., Apfelstedt-Sylla, E., Hergersberg, M., Lorenz, B., Wissinger, B., Wittwer, B., Rudolph, G., Meindl, A., Meitinger, T. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  29. Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa. Miano, M.G., Testa, F., Strazzullo, M., Trujillo, M., De Bernardo, C., Grammatico, B., Simonelli, F., Mangino, M., Torrente, I., Ruberto, G., Beneyto, M., Antinolo, G., Rinaldi, E., Danesino, C., Ventruto, V., D'Urso, M., Ayuso, C., Baiget, M., Ciccodicola, A. Eur. J. Hum. Genet. (1999) [Pubmed]
  30. Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp. Hardcastle, A.J., David-Gray, Z.K., Jay, M., Bird, A.C., Bhattacharya, S.S. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  31. Identification of a novel protein interacting with RPGR. Boylan, J.P., Wright, A.F. Hum. Mol. Genet. (2000) [Pubmed]
  32. Novel deletion spanning RCC1-like domain of RPGR in Japanese X-linked retinitis pigmentosa family. Jin, Z.B., Liu, X.Q., Uchida, A., Vervoort, R., Morishita, K., Hayakawa, M., Murakami, A., Matsumoto, N., Niikawa, N., Nao-i, N. Mol. Vis. (2005) [Pubmed]
  33. A presumed missense mutation of RPGR causes abnormal RNA splicing with exon skipping. Demirci, F.Y., Radak, A.L., Rigatti, B.W., Mah, T.S., Gorin, M.B. Am. J. Ophthalmol. (2004) [Pubmed]
  34. DNA sequence comparison of human and mouse retinitis pigmentosa GTPase regulator (RPGR) identifies tissue-specific exons and putative regulatory elements. Kirschner, R., Erturk, D., Zeitz, C., Sahin, S., Ramser, J., Cremers, F.P., Ropers, H.H., Berger, W. Hum. Genet. (2001) [Pubmed]
  35. X-linked recessive atrophic macular degeneration from RPGR mutation. Ayyagari, R., Demirci, F.Y., Liu, J., Bingham, E.L., Stringham, H., Kakuk, L.E., Boehnke, M., Gorin, M.B., Richards, J.E., Sieving, P.A. Genomics (2002) [Pubmed]
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