Alternative titles; symbols
HGNC Approved Gene Symbol: RBP3
Cytogenetic location: 10q11.22 Genomic coordinates (GRCh38): 10:47,348,363-47,357,881 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 10q11.22 | ?Retinitis pigmentosa 66 | 615233 | Autosomal recessive | 3 |
Interstitial retinoid-binding protein (IRBP, RBP3) is a large soluble single-subunit glycoprotein that is synthesized and secreted by rod photoreceptor cells into the interphotoreceptor matrix. It is known to bind retinoids and fatty acids (summary by Liou et al., 1989).
Liou et al. (1989) determined that the IRBP gene encodes a deduced 1,230-amino acid protein with a calculated molecular mass of 133 kD.
Liou et al. (1989) found that the IRBP gene spans more than 11 kb and is interrupted by 3 introns, all of which are positioned near the 3-prime end of the coding sequence.
Liou et al. (1987) described a Bgl II RFLP in the gene that codes for human interstitial retinol-binding protein. By study of somatic cell hybrids, they mapped the IRBP (RBP3) gene to chromosome 10. By in situ hybridization, they localized it to 10p11.2-q11.2, with a secondary site of hybridization at 10q24-q25.
Chin et al. (1988) described a RFLP recognized by a human IRBP cDNA.
Danciger et al. (1990) assigned the murine homolog, Rbp3, to mouse chromosome 14 at a position near Np1. Thus, the NP gene (164050) on human chromosome 14 and the RBP3 gene on human chromosome 10 flank the site of a putative chromosomal translocation that contributed to divergent karyotype evolution of man and mouse. Mapping of multiple genes on chromosome 10 (Farrer et al., 1988; Nakamura et al., 1988; Carson and Simpson, 1989) suggests that the most likely location of RBP3 is 10q11.2.
Fong et al. (1984) presented evidence indicating that RBP3 is involved in the transfer of retinol between the pigment epithelium and retina during the visual cycle.
In a consanguineous Italian family with retinitis pigmentosa mapping to chromosome 10 (RP66; 615233), den Hollander et al. (2009) analyzed 3 candidate genes and identified a missense mutation in the RBP3 gene (D1080N; 180290.0001) that segregated with disease and was not found in 116 Italian controls or 94 controls of mixed North American ancestry. Analysis of RBP3 in 395 additional unrelated patients with recessive or sporadic RP and in 680 patients with other forms of hereditary retinal degeneration revealed no mutations.
Liou et al. (1998) generated transgenic mice with targeted disruption of the IRBP gene. As early as postnatal day 11, histologic examination of the retinas of IRBP -/- mice revealed a loss of photoreceptor nuclei and changes in the structural integrity of the receptor outer segments. At 30 days of age, the photoreceptor abnormalities in the null mice were more severe, and electroretinographic recordings revealed a marked loss in photic sensitivity. In contrast, no morphologic or electrophysiologic changes were detected in age-matched heterozygotes. Liou et al. (1998) concluded that normal photoreceptor development and function are highly dependent on early expression of IRBP, and that in the absence of IRBP there is a slowly progressive degeneration of retinal photoreceptors.
In 4 sibs from a consanguineous Italian family with retinitis pigmentosa (RP66; 615233), den Hollander et al. (2009) identified homozygosity for a c.3238G-A transition in exon 2 of the RBP3 gene, resulting in an asp1080-to-asn (D1080N) substitution at a highly conserved residue in the fourth IRBP repeat module. The mutation was not found in 116 Italian controls without known photoreceptor disease or 94 controls of mixed North American ancestry.
In transiently transfected mouse photoreceptor-derived cells, Li et al. (2013) demonstrated that the D1080N mutation abolishes secretion of RBP3, and immunoblot analysis revealed that the mutant RBP3 forms insoluble high molecular weight complexes via disulfide bonds. Confocal microscopy showed that the mutant protein was not transported to the Golgi apparatus, but accumulated in the endoplasmic reticulum. In addition, the D1080N mutant induced upregulation and nuclear translocation of CHOP (DDIT3; 126337), a proapoptotic transcription factor associated with the unfolded protein response. Chemical chaperones and low temperature significantly rescued the secretion of the mutant protein, suggesting that misfolding is the molecular basis for the pathogenicity of D1080N substitution.
Carson, N. L., Simpson, N. E. A physical map of 13 markers on chromosome 10 from dosage studies on abnormal cell lines. (Abstract) Cytogenet. Cell Genet. 51: 974-975, 1989.
Chin, K. S., Mathew, C. G. P., Fong, S. L., Bridges, C. D. B., Ponder, B. A. J. Styl RFLP recognised by a human IRBP cDNA localised to chromosome 10. Nucleic Acids Res. 16: 1645 only, 1988. [PubMed: 2894635] [Full Text: https://doi.org/10.1093/nar/16.4.1645]
Danciger, M., Kozak, C. A., Nickerson, J., Redmond, T. M., Farber, D. B. Localization of the gene for interphotoreceptor retinoid-binding protein to mouse chromosome 14 near Np-1. Genomics 8: 727-731, 1990. [PubMed: 2276745] [Full Text: https://doi.org/10.1016/0888-7543(90)90262-s]
den Hollander, A. I., McGee, T. L., Ziviello, C., Banfi, S., Dryja, T. P., Gonzalez-Fernandez, F., Ghosh, D., Berson, E. L. A homozygous missense mutation in the IRBP gene (RBP3) associated with autosomal recessive retinitis pigmentosa. Invest. Ophthal. Vis. Sci. 50: 1864-1872, 2009. [PubMed: 19074801] [Full Text: https://doi.org/10.1167/iovs.08-2497]
Farrer, L. A., Castiglione, C. M., Kidd, J. R., Myers, S., Carson, N., Simpson, N. E., Kidd, K. K. A linkage group of five DNA markers on human chromosome 10. Genomics 3: 72-77, 1988. [PubMed: 2906045] [Full Text: https://doi.org/10.1016/0888-7543(88)90162-0]
Fong, S.-L., Liou, G. I., Landers, R. A., Alvarez, R. A., Gonzalez-Fernandez, F., Glazebrook, P. A., Lam, D. M. K., Bridges, C. D. B. Characterization, localization, and biosynthesis of an interstitial retinol-binding glycoprotein in the human eye. J. Neurochem. 42: 1667-1676, 1984. [PubMed: 6427409] [Full Text: https://doi.org/10.1111/j.1471-4159.1984.tb12758.x]
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]
Li, S., Yang, Z., Hu, J., Gordon, W. C., Bazan, N. G., Haas, A. L., Bok, D., Jin, M. Secretory defect and cytotoxicity: the potential disease mechanisms for the retinitis pigmentosa (RP)-associated interphotoreceptor retinoid-binding protein (IRBP). J. Biol. Chem. 288: 11395-11406, 2013. [PubMed: 23486466] [Full Text: https://doi.org/10.1074/jbc.M112.418251]
Liou, G. I., Fei, Y., Peachey, N. S., Matragoon, S., Wei, S., Blaner, W. S., Wang, Y., Liu, C., Gottesman, M. E., Ripps, H. Early onset photoreceptor abnormalities induced by targeted disruption of the interphotoreceptor retinoid-binding protein gene. J. Neurosci. 18: 4511-4520, 1998. [PubMed: 9614228] [Full Text: https://doi.org/10.1523/JNEUROSCI.18-12-04511.1998]
Liou, G. I., Fong, S.-L., Beattie, W. G., Cook, R. G., Leone, J., Landers, R. A., Alvarez, R. A., Wang, C., Li, Y., Bridges, C. D. B. Bovine interstitial retinol-binding protein (IRBP)--isolation and sequence analysis of cDNA clones, characterization and in vitro translation of mRNA. Vision Res. 26: 1645-1653, 1986. [PubMed: 3617506] [Full Text: https://doi.org/10.1016/0042-6989(86)90052-0]
Liou, G. I., Fong, S.-L., Gosden, J., vanTuinen, P., Ledbetter, D. H., Christie, S., Rout, D., Bhattacharya, S., Cook, R. G., Li, Y., Wang, C., Bridges, C. D. B. Human interstitial retinol-binding protein (IRBP): cloning, partial sequence, and chromosomal localization. Somat. Cell Molec. Genet. 13: 315-323, 1987. [PubMed: 3455009] [Full Text: https://doi.org/10.1007/BF01534925]
Liou, G. I., Li, Y., Wang, C., Fong, S.-L., Bhattacharya, F. S., Bridges, C. D. B. Bgl II RFLP recognized by a human IRBP cDNA localized to chromosome 10. Nucleic Acids Res. 15: 3196 only, 1987. [PubMed: 2882488] [Full Text: https://doi.org/10.1093/nar/15.7.3196]
Liou, G. I., Ma, D.-P., Yang, Y.-W., Geng, L., Zhu, C., Baehr, W. Human interstitial retinoid-binding protein: gene structure and primary sequence. J. Biol. Chem. 264: 8200-8206, 1989. [PubMed: 2542268]
Nakamura, Y., Lathrop, M., Bragg, T., Leppert, M., O'Connell, P., Jones, C., Lalouel, J. M., White, R. An extended genetic linkage map of markers for human chromosome 10. Genomics 3: 389-392, 1988. [PubMed: 2907505] [Full Text: https://doi.org/10.1016/0888-7543(88)90133-4]