Alternative titles; symbols
HGNC Approved Gene Symbol: GUCY2F
Cytogenetic location: Xq22.3-q23 Genomic coordinates (GRCh38): X:109,372,906-109,482,086 (from NCBI)
Light activation of the visual signal transduction cascade results in transient membrane hyperpolarization of photoreceptors. This process is initiated by a heterotrimeric G protein-coupled pathway that activates hydrolysis of cGMP, resulting in closure of the cGMP-gated cation channel in the plasma membrane. Resynthesis of cGMP by guanylyl cyclase (GC) results in channel opening and recovery of the dark state. The RetGC (GUCY2D; 600179) guanylyl cyclase is expressed predominantly in photoreceptors. By screening a retina library with cDNAs encoding the cytoplasmic domains of RetGC and 3 other GCs, Lowe et al. (1995) isolated cDNAs encoding a novel membrane GC. They designated the predicted 1,108-amino acid protein RetGC2 because it was most closely related to RetGC; they suggested that RetGC be renamed RetGC1. RetGC2 contains a 50-amino acid signal sequence, a transmembrane region, a kinase homology domain, and a cyclase domain. It migrated as an approximately 115-kD protein on Western blots of bovine rod outer segments. Membrane GC activity of recombinant RetGC2 protein expressed in mammalian cells was stimulated by bovine p24, the retinal cyclase activator, in a calcium-sensitive manner. In situ hybridization to monkey tissues revealed that RetGC2 mRNA is found only in the outer nuclear layer and inner segments of photoreceptor cells.
Yang et al. (1995) isolated 2 guanylyl cyclases (GC-E (see 600179) and GC-F) from a rat eye cDNA library. Both genes are expressed in retina.
By interspecific backcross analysis, Yang et al. (1996) mapped the mouse Gucy2f gene to the X chromosome. They localized the human GUCY2F gene to Xq22 by fluorescence in situ hybridization. Two forms of retinitis pigmentosa, RP2 (312600) and RP3 (300029), had been mapped to Xp. In a study of 40 X-linked kindreds, Teague et al. (1994) demonstrated that some are definitely not linked to either locus and others may not be linked. Yang et al. (1996) stated that GUCY2F is a candidate gene for X-linked retinitis pigmentosa.
Lowe, D. G., Dizhoor, A. M., Liu, K., Gu, Q., Spencer, M., Laura, R., Lu, L., Hurley, J. B. Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. Proc. Nat. Acad. Sci. 92: 5535-5539, 1995. [PubMed: 7777544] [Full Text: https://doi.org/10.1073/pnas.92.12.5535]
Teague, P. W., Aldred, M. A., Jay, M., Dempster, M., Harrison, C., Carothers, A. D., Hardwick, L. J., Evans, H. J., Strain, L., Brock, D. J. H., Bundey, S., Jay, B., Bird, A. C., Bhattacharya, S. S., Wright, A. F. Heterogeneity analysis in 40 X-linked retinitis pigmentosa families. Am. J. Hum. Genet. 55: 105-111, 1994. [PubMed: 8023838]
Yang, R.-B., Foster, D. C., Garbers, D. L., Fulle, H.-J. Two membrane forms of guanylyl cyclase found in the eye. Proc. Nat. Acad. Sci. 92: 602-606, 1995. [PubMed: 7831337] [Full Text: https://doi.org/10.1073/pnas.92.2.602]
Yang, R.-B., Fulle, H.-J., Garbers, D. L. Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina. Genomics 31: 367-372, 1996. [PubMed: 8838319] [Full Text: https://doi.org/10.1006/geno.1996.0060]