Alternative titles; symbols
HGNC Approved Gene Symbol: GUCA1B
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:42,183,284-42,194,956 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p21.1 | Retinitis pigmentosa 48 | 613827 | Autosomal dominant | 3 |
GUCA1B is a neuronal calcium sensor that confers Ca(2+) sensitivity to retina-specific guanylyl cyclases (e.g., GUCY2D; 600179), which support synthesis of cyclic GMP (cGMP) in photoreceptors (Makino et al., 2008).
By Northern blot analysis, Surguchov et al. (1997) detected a 2.2-kb GUCA1B mRNA in retina only.
Using somatic human-hamster hybrid analysis and fluorescence in situ hybridization, Surguchov et al. (1997) mapped the GUCA1B gene to chromosome 6p21.1. PCR analysis showed that the GUCA1B gene is arranged in a tail-to-tail array with the related GUCA1A gene (600364), consistent with a gene duplication event.
Payne et al. (1999) reported mutation analysis of the GUCA1B gene in 400 unrelated British individuals with autosomal dominant central and peripheral retinal dystrophies. A number of sequence changes and polymorphisms, but no disease-causing mutations, were found.
Sato et al. (2005) screened 96 unrelated Japanese patients with retinitis pigmentosa for mutations in the GUCA1B gene and identified heterozygosity for a G157R mutation (602275.0001) in 3.
Using a stepwise molecular screening method in a cohort of 369 Japanese probands with inherited retinal dystrophy, Arai et al. (2015) identified the G157R mutation in 4 patients with retinitis pigmentosa.
Makino et al. (2008) found that Gcap2 knockout in mice did not compromise rod viability or alter outer segment ultrastructure. However, maximal retinal guanylyl cyclase activity activity at low Ca(2+) was suppressed 2-fold in Gcap2-knockout mice, and the half-maximal rate of cGMP synthesis was attained at a higher than normal Ca(2+) concentration. Recombinant bovine or mouse Gcap2 restored the high maximal retinal guanylyl cyclase activity in Gcap2-knockout homogenate. Addition of antibody against mouse Gcap2 in wildtype retina produced effects on guanylyl cyclase activity similar to those observed in Gcap2-knockout mice. Flash responses of Gcap2-knockout rods recovered more slowly than normal. Gcap2-knockout rods became more sensitive to flashes and to steps of illumination, but they tended to saturate at lower intensities, compared with wildtype rods. The authors concluded that GCAP2 regulation of guanylyl cyclase activity quickens the recovery of flash and step responses and adjusts the operating range of rods to higher intensities of ambient illumination.
In 7 patients from 3 unrelated Japanese families with retinitis pigmentosa, with or without macular involvement (RP48; 613827), Sato et al. (2005) demonstrated a novel c.156G-A transition in the GUCA1B gene, resulting in a gly157-to-arg (G157R) substitution. These families demonstrated variable phenotypic expression and incomplete penetrance of the retinitis pigmentosa phenotype.
Using a stepwise molecular screening method in a cohort of 369 Japanese probands with inherited retinal dystrophy, Arai et al. (2015) identified the G157R mutation in 4 patients with retinitis pigmentosa.
Hamosh (2018) noted that the c.156G-A variant was found in 13 of 8,646 East Asian alleles, with an allele frequency of 0.0015, in the ExAC database (April 30, 2018).
Arai, Y., Maeda, A., Hirami, Y., Ishigami, C., Kosugi, S., Mandai, M. Kurimoto, Y., Takahashi, M. Retinitis pigmentosa with EYS mutations is the most prevalent inherited retinal dystrophy in Japanese populations. J. Ophthal. 2015: 819760, 2015. Note: Electronic Article. [PubMed: 26161267] [Full Text: https://doi.org/10.1155/2015/819760]
Hamosh, A. Personal Communication. Baltimore, Md. April 30, 2018.
Makino, C. L., Peshenko, I. V., Wen, X.-H., Olshevskaya, E. V., Barrett, R., Dizhoor, A. M. A role for GCAP2 in regulating the photoresponse: guanylyl cyclase activation and rod electrophysiology in GUCA1B knockout mice. J. Biol. Chem. 283: 29135-29143, 2008. [PubMed: 18723510] [Full Text: https://doi.org/10.1074/jbc.M804445200]
Payne, A. M., Downes, S. M., Bessant, D. A. R., Plant, C., Moore, T., Bird, A. C., Bhattacharya, S. S. Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies. J. Med. Genet. 36: 691-693, 1999. [PubMed: 10507726]
Sato, M., Nakazawa, M., Usui, N., Tanimoto, N., Abe, H., Ohguro, H. Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B gene) in patients with autosomal dominant retinal dystrophies. Graefes Arch. Clin. Exp. Ophthalmol. 243: 235-242, 2005. [PubMed: 15452722] [Full Text: https://doi.org/10.1007/s00417-004-1015-7]
Surguchov, A., Bronson, J. D., Banerjee, P., Knowles, J. A., Ruiz, C., Subbaraya, I., Palczewski, K., Baehr, W. The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on the short arm of chromosome 6 (p21.1). Genomics 39: 312-322, 1997. [PubMed: 9119368] [Full Text: https://doi.org/10.1006/geno.1996.4513]