Alternative titles; symbols
HGNC Approved Gene Symbol: RGR
Cytogenetic location: 10q23.1 Genomic coordinates (GRCh38): 10:84,245,053-84,259,960 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q23.1 | Retinitis pigmentosa 44 | 613769 | 3 |
RPE-retinal G protein-coupled receptor (RGR) is a rhodopsin homolog found exclusively in cells adjacent to the retinal photoreceptor cells (i.e., the retinal pigment epithelium and Muller cells). It preferentially binds all-trans retinal rather than 11-cis retinal, which is normally found in rhodopsin. In mammals, photons of light convert all-trans retinal within RGR to 11-cis retinal, whereas the reverse isomerization reaction occurs in rhodopsin in photoreceptor cells (summary by Morimura et al., 1999).
The retinal pigment epithelium (RPE) is a specialized cell monolayer that lies adjacent to the photoreceptors and performs functions that are essential to the visual process. One function of the RPE is to restore the chromophore 11-cis-retinal from its all-trans configuration and allow synthesis and regeneration of the visual pigments. Jiang et al. (1993) identified an opsin-related gene that is preferentially expressed at high levels in the RPE and Muller cells of the neural retina. The gene encodes a putative RPE-retinal G protein-coupled receptor (RGR) with 7 transmembrane segments. The putative receptor most closely resembled the subfamily of visual pigments and retinochromes.
Shen et al. (1994) found that the amino acid sequence of RGR in humans is 86% identical to that of bovine RGR and that a lysine residue, analogous to the retinaldehyde attachment site of rhodopsin (180380), is conserved in the seventh transmembrane domain of RGR in both species.
During visual excitation, rhodopsin (180380) undergoes photoactivation and bleaches to opsin and all-trans-retinal. To regenerate rhodopsin and maintain normal visual sensitivity, the all-trans isomer must be metabolized and reisomerized to produce the chromophore 11-cis-retinal. Chen et al. (2001) showed that RGR is involved in the formation of 11-cis-retinal in mice and functions in a light-dependent pathway of the rod visual cycle.
Bailey and Cassone (2004) characterized the Rgr and Rrh (605224) genes in the chick. Northern blot and in situ analyses revealed expression of both opsins in the pineal gland, retina, and brain tissue. The mRNA for both genes within the pineal gland and retina were regulated on a circadian basis and were highest late in the subjective day.
Shen et al. (1994) determined that the human RGR gene spans 14.8 kb and is split into 7 exons. The structure of the gene is distinct from that of the visual pigment genes. Shen et al. (1994) suggested that the RGR gene represents the earliest independent branch of the vertebrate opsin gene family. A second form of human RGR in retina was predicted by alternative splicing of its precursor mRNA. This RGR variant resulted from the alternative use of an internal acceptor splice site in the second intron of the human gene, and it contained an insertion of 4 amino acids in the connecting loop between the second and third transmembrane domains.
Chen et al. (1996) localized the human RGR gene to chromosome 10q23 by FISH, using both cDNA and genomic DNA probes.
In a screen of the RGR gene in 747 patients with various forms of retinitis pigmentosa (RP), 95 patients with other retinal degenerative disorders, and approximately 95 controls, Morimura et al. (1999) identified 2 probands with RP and mutation in the RGR gene. One index patient with recessive RP was homozygous for a ser66-to-arg missense mutation (600342.0001). A second patient, originally diagnosed with choroidal sclerosis (see 303100), was heterozygous for a 1-bp insertion in codon gly275 (GGA-to-GGGA) near the 3-prime end of the coding region (600342.0002). Both affected sibs were heterozygotes and an unaffected sib was homozygous wildtype. The deceased father was said to have been affected, making it likely that the retinal degeneration in this family is dominantly inherited. Morimura et al. (1999) detected no alteration of the other allele in the 2 affected individuals or in unaffected members of this family.
Using D-HPLC and direct sequencing, Ksantini et al. (2010) analyzed the RGR gene in 134 patients with autosomal recessive or sporadic RP, 79 cases with autosomal dominant RP, 36 RP cases with undetermined inheritance, and 113 patients with other retinal dystrophies, but did not find any pathogenic mutations. The authors concluded that mutations in RGR occur rarely in inherited retinal dystrophies.
In 5 sibs with retinitis pigmentosa (RP44; 613769), Morimura et al. (1999) identified a homozygous A-to-C transversion in the RGR gene resulting in a ser66-to-arg (S66R) amino acid substitution. The parents denied consanguinity. Haplotype analyses suggested that the mutant allele in the parents had a common ancestral origin. The patients in this family, aged 35 to 44, with the ser66-to-arg mutation had visual acuity of 20/200 or worse, severely constricted visual fields, attenuated retinal vessels, diffuse depigmentation of the retinal pigment epithelium, and intraretinal pigment deposits in the periphery. The depigmented patches involved the central macula in those sibs with severely decreased acuity. Full-field electroretinograms reflected widespread loss of photoreceptor function.
In a patient with retinitis pigmentosa (RP44; 613769), Morimura et al. (1999) found a 1-bp insertion in codon gly275 (GGA-to-GGGA) near the 3-prime end of the coding region of the RGR gene. The patient had originally been diagnosed with choroidal sclerosis (see 215500). Both affected sibs were heterozygotes and an unaffected sib was homozygous wildtype. The deceased father was said to have been affected by this apparently dominantly inherited disorder. Morimura et al. (1999) detected no alteration of the other allele in the affected sibs.
Bailey, M. J., Cassone, V. M. Opsin photoisomerases in the check retina and pineal gland: characterization, localization, and circadian regulation. Invest. Ophthal. Vis. Sci. 45: 769-755, 2004. [PubMed: 14985289] [Full Text: https://doi.org/10.1167/iovs.03-1125]
Chen, P., Hao, W., Rife, L., Wang, X. P., Shen, D., Chen, J., Ogden, T., Van Boemel, G. B., Wu, L., Yang, M., Fong, H. K. W. A photic visual cycle of rhodopsin regeneration is dependent on Rgr. Nature Genet. 28: 256-260, 2001. [PubMed: 11431696] [Full Text: https://doi.org/10.1038/90089]
Chen, X.-N., Korenberg, J. R., Jiang, M., Shen, D., Fong, H. K. W. Localization of the human RGR opsin gene to chromosome 10q23. Hum. Genet. 97: 720-722, 1996. [PubMed: 8641686] [Full Text: https://doi.org/10.1007/BF02346179]
Jiang, M., Pandey, S., Fong, H. K. W. An opsin homologue in the retina and pigment epithelium. Invest. Ophthal. Vis. Sci. 34: 3669-3678, 1993. [PubMed: 8258527]
Ksantini, M., Senechal, A., Bocquet, B., Meunier, I., Brabet, P., Hamel, C. P. Screening genes of the visual cycle RGR, RBP1 and RBP3 identifies rare sequence variations. Ophthal. Genet. 31: 200-204, 2010. [PubMed: 21067480] [Full Text: https://doi.org/10.3109/13816810.2010.512354]
Morimura, H., Saindelle-Ribeaudeau, F., Berson, E. L., Dryja, T. P. Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa. (Letter) Nature Genet. 23: 393-394, 1999. [PubMed: 10581022] [Full Text: https://doi.org/10.1038/70496]
Shen, D., Jiang, M., Hao, W., Tao, L., Salazar, M., Fong, H. K. W. A human opsin-related gene that encodes a retinaldehyde-binding protein. Biochemistry 33: 13117-13125, 1994. [PubMed: 7947717] [Full Text: https://doi.org/10.1021/bi00248a022]