RPGRIP1 gene


Gene (OMIM no.)
Function of gene/protein
  • Protein: retinitis pigmentosa GTPases regulator-interacting protein
  • Localised to the connecting cilium of photoreceptors
  • A scaffold protein required for normal photoreceptor outer segment disk morphogenesis and organisation
  • Anchoring the RPGR protein to the connecting cilium
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Signs for LCA
  • Nystagmus
  • Profound visual deficiency
  • Oculodigital sign
  • Photophobia initially
  • Nyctalopia may be reported later on
  • Hypermetropia (<+7.00D)
  • Mild vessel attenuation initially progressing to optic disc pallor, RPE mottling and peripheral pigmentations with retinal degeneration (2nd to 3rd decade of life)
  • Macular atrophy may develop in later stages
  • Keratoconus
  • Cataract
Signs for cone-rod dystrophy
  • Early onset severe photophobia
  • Dyschromatopsia
  • Variable degree of fundus granularity and macular degeneration
  • Bull’s eye maculopathy seen in one patient
Visual functionLCA:
  • Initial rapid decline in visual function followed by lack of progression (VA 6/60 or worse)
Cone-rod dystrophy:
  • Deterioration of central vision and colour blindness from an early age; rapid loss of VA around mid-teens to BCVA 1/60
Systemic features
  • No extraocular features reported
Key investigations
  • Full field ERG: Unrecordable or cone-rod dystrophy
  • Pattern ERG
  • FAF to detect areas of RPE atrophy
  • OCT: Relatively preserved foveal outer retinal lamination including the ellipsoid zone (EZ) but progressive EZ loss and outer nuclear layer thinning in the parafoveal and perifoveal regions
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
Further information

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Additional information

Most of the reported RPGRIP1 variants cause an LCA phenotype, accounting for 5-6% of total LCA cases.[1] LCA variants tend to cause severely reduced or absent RPGRIP1 protein function (null mutations) while CORD is linked to missense variants that likely retain partial protein function.[1] 

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  1.  Li T. Leber congenital amaurosis caused by mutations in RPGRIP1. Cold Spring Harb Perspect Med. 2014;5(4). doi:10.1101/cshperspect.a017384
  2.  Hanein S, Perrault I, Gerber S, et al. Leber congenital amaurosis: Comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. Hum Mutat. 2004;23(4):306-317. doi:10.1002/humu.20010
  3.  McKibbin M, Ali M, Mohamed MD, et al. Genotype-phenotype correlation for leber congenital amaurosis in Northern Pakistan. Arch Ophthalmol. 2010;128(1):107-113
  4.  Khan AO, Abu-Safieh L, Eisenberger T, Bolz HJ, Alkuraya FS. The RPGRIP1-related retinal phenotype in children [published correction appears in Br J Ophthalmol. 2014 Mar;98(3):420]. Br J Ophthalmol. 2013;97(6):760-764
  5.  Jacobson SG, Cideciyan AV, Aleman TS, et al. Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential. Ophthalmology. 2007;114(5):895-898
  6.  Miyamichi D, Nishina S, Hosono K, et al. Retinal structure in Leber’s congenital amaurosis caused by RPGRIP1 mutations. Hum Genome Var. 2019;6:32
  7.  Hameed A, Abid A, Aziz A, Ismail M, Mehdi SQ, Khaliq S. Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy. J Med Genet. 2003;40(8):616-619. doi:10.1136/jmg.40.8.616

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Updated on November 30, 2020
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