{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:54:12Z","timestamp":1791071652191,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,12,20]]},"abstract":"<jats:p>\n                    RPGR-interacting protein 1 (RPGRIP1) is a key component of cone and rod photoreceptor cells, where it interacts with RPGR (retinitis pigmentosa GTPase regulator). Mutations in\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    lead to autosomal recessive congenital blindness [Leber congenital amaurosis (LCA)]. Most LCA-associated missense mutations in\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    are located in a segment that encodes two C2 domains. Based on the C2 domain of novel protein kinase C\u03b5 (PKC\u03b5), we built a 3D-homology model for the C-terminal C2 domain of RPGRIP1. This model revealed a potential Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -binding site that was predicted to be disrupted by a missense mutation in\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    , which was previously identified in an LCA patient. Through yeast two-hybrid screening of a retinal cDNA library, we found this C2 domain to specifically bind to nephrocystin-4, encoded by\n                    <jats:italic>NPHP4<\/jats:italic>\n                    . Mutations in\n                    <jats:italic>NPHP4<\/jats:italic>\n                    are associated with nephronophthisis and a combination of nephronophthisis and retinitis pigmentosa called Senior\u2013L\u00f8ken syndrome (SLSN). We show that RPGRIP1 and nephrocystin-4 interact strongly\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and that they colocalize in the retina, matching the panretinal localization pattern of specific RPGRIP1 isoforms. Their interaction is disrupted by either mutations in\n                    <jats:italic>RPGRIP1<\/jats:italic>\n                    , found in patients with LCA, or by mutations in\n                    <jats:italic>NPHP4<\/jats:italic>\n                    , found in patients with nephronophthisis or SLSN. Thus, we provide evidence for the involvement of this disrupted interaction in the retinal dystrophy of both SLSN and LCA patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0505774102","type":"journal-article","created":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T20:43:46Z","timestamp":1134161026000},"page":"18520-18525","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":106,"title":["Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations"],"prefix":"10.1073","volume":"102","author":[{"given":"Ronald","family":"Roepman","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stef J. F.","family":"Letteboer","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen H.","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E. C.","family":"van Beersum","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmar","family":"Krieger","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo A.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans P. M.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands; Departments of Ophthalmology and Molecular Genetics and Microbiology, Duke University Medical Center, Erwin Road, Durham, NC 27710; and Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, P.O. 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