Reviewed August 2010
What is the official name of the GUCY2D gene?
The official name of this gene is “guanylate cyclase 2D, membrane (retina-specific).”
GUCY2D is the gene's official symbol. The GUCY2D gene is also known by other names, listed below.
What is the normal function of the GUCY2D gene?
The GUCY2D gene provides instructions for making a protein that plays an essential role in normal vision. This protein is found in the retina, which is the specialized tissue at the back of the eye that detects light and color. Within the retina, the GUCY2D protein is located in light-detecting cells called photoreceptors. The retina contains two types of photoreceptor cells: rods and cones. Rods are needed for vision in low light, while cones are needed for vision in bright light, including color vision.
The GUCY2D protein is involved in a process called phototransduction. When light enters the eye, it stimulates specialized pigments in photoreceptor cells. This stimulation triggers a series of chemical reactions that produce an electrical signal, which is interpreted by the brain as vision. Once photoreceptors have been stimulated by light, they must return to their resting (or "dark") state before they can be stimulated again. The GUCY2D protein is responsible for a chemical reaction that helps return photoreceptors to their dark state after light exposure.
How are changes in the GUCY2D gene related to health conditions?
- Leber congenital amaurosis - caused by mutations in the GUCY2D gene
More than 50 mutations in the GUCY2D gene have been found to cause Leber congenital amaurosis. Mutations in this gene account for 6 to 21 percent of all cases of this condition.
The mutations responsible for Leber congenital amaurosis occur in both copies of the GUCY2D gene in each cell. Most of these genetic changes lead to an abnormally short, nonfunctional version of the GUCY2D protein. A lack of this protein prevents photoreceptor cells from returning to their dark state after they are exposed to light. As a result, the process of phototransduction is almost totally shut down, leading to severe visual impairment beginning very early in life.
- other disorders - caused by mutations in the GUCY2D gene
At least six mutations in the GUCY2D gene have been identified in people with another vision disorder called cone-rod dystrophy. The vision problems associated with this condition include a loss of sharpness (reduced acuity), an increased sensitivity to light (photophobia), nearsightedness (myopia), and impaired color vision. These vision problems tend to worsen over time.
Most of the GUCY2D gene mutations responsible for cone-rod dystrophy affect a particular protein building block (amino acid) in the GUCY2D protein, replacing the amino acid arginine at position 838 with one of several other amino acids. A few mutations alter other amino acids in the same region of the protein.
The mutations that cause cone-rod dystrophy typically occur in one of the two copies of the GUCY2D gene in each cell. These genetic changes impair normal phototransduction, which causes the progressive vision problems found in cone-rod dystrophy.
Where is the GUCY2D gene located?
Cytogenetic Location: 17p13.1
Molecular Location on chromosome 17: base pairs 8,002,670 to 8,020,340
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/3000))
The GUCY2D gene is located on the short (p) arm of chromosome 17 at position 13.1.
More precisely, the GUCY2D gene is located from base pair 8,002,670 to base pair 8,020,340 on chromosome 17.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about GUCY2D?
You and your healthcare professional may find the following resources about GUCY2D helpful.
Educational resources - Information pages
- Foundation Fighting Blindness: Cone-Rod Dystrophy (http://www.blindness.org/eye-conditions/cone-rod-dystrophy)
- National Eye Institute: Diagram of the Eye (https://nei.nih.gov/health/eyediagram/)
- Neuroscience (second edition, 2001): The Retina (http://www.ncbi.nlm.nih.gov/books/NBK10885/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1298)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for GUCY2D (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=3000%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28GUCY2D%5BTIAB%5D%29%20OR%20%28RETGC-1%5BTIAB%5D%29%20OR%20%28RETGC1%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- CONE-ROD DYSTROPHY 6 (http://omim.org/entry/601777)
- GUANYLATE CYCLASE 2D, MEMBRANE (http://omim.org/entry/600179)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_GUCY2D.html)
- HGNC Gene Family: Guanylate cyclase receptors (http://www.genenames.org/cgi-bin/genefamilies/set/343)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4689)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3000)
What other names do people use for the GUCY2D gene or gene products?
- guanylate cyclase 2D, retinal
- retinal guanylyl cyclase 1
- rod outer segment membrane guanylate cyclase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding GUCY2D?
amino acid ;
You may find definitions for these and many other terms in the Genetics Home Reference
- den Hollander AI, Roepman R, Koenekoop RK, Cremers FP. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res. 2008 Jul;27(4):391-419. doi: 10.1016/j.preteyeres.2008.05.003. Epub 2008 Jun 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18632300?dopt=Abstract)
- Hanein S, Perrault I, Olsen P, Lopponen T, Hietala M, Gerber S, Jeanpierre M, Barbet F, Ducroq D, Hakiki S, Munnich A, Rozet JM, Kaplan J. Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin. Hum Mutat. 2002 Oct;20(4):322-3. (http://www.ncbi.nlm.nih.gov/pubmed/12325031?dopt=Abstract)
- Ito S, Nakamura M, Ohnishi Y, Miyake Y. Autosomal dominant cone-rod dystrophy with R838H and R838C mutations in the GUCY2D gene in Japanese patients. Jpn J Ophthalmol. 2004 May-Jun;48(3):228-35. (http://www.ncbi.nlm.nih.gov/pubmed/15175914?dopt=Abstract)
- Kelsell RE, Gregory-Evans K, Payne AM, Perrault I, Kaplan J, Yang RB, Garbers DL, Bird AC, Moore AT, Hunt DM. Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy. Hum Mol Genet. 1998 Jul;7(7):1179-84. (http://www.ncbi.nlm.nih.gov/pubmed/9618177?dopt=Abstract)
- Kitiratschky VB, Wilke R, Renner AB, Kellner U, Vadalà M, Birch DG, Wissinger B, Zrenner E, Kohl S. Mutation analysis identifies GUCY2D as the major gene responsible for autosomal dominant progressive cone degeneration. Invest Ophthalmol Vis Sci. 2008 Nov;49(11):5015-23. doi: 10.1167/iovs.08-1901. Epub 2008 May 16. (http://www.ncbi.nlm.nih.gov/pubmed/18487367?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3000)
- Payne AM, Morris AG, Downes SM, Johnson S, Bird AC, Moore AT, Bhattacharya SS, Hunt DM. Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies. J Med Genet. 2001 Sep;38(9):611-4. (http://www.ncbi.nlm.nih.gov/pubmed/11565546?dopt=Abstract)
- Perrault I, Rozet JM, Gerber S, Ghazi I, Ducroq D, Souied E, Leowski C, Bonnemaison M, Dufier JL, Munnich A, Kaplan J. Spectrum of retGC1 mutations in Leber's congenital amaurosis. Eur J Hum Genet. 2000 Aug;8(8):578-82. (http://www.ncbi.nlm.nih.gov/pubmed/10951519?dopt=Abstract)
- Perrault I, Rozet JM, Gerber S, Kelsell RE, Souied E, Cabot A, Hunt DM, Munnich A, Kaplan J. A retGC-1 mutation in autosomal dominant cone-rod dystrophy. Am J Hum Genet. 1998 Aug;63(2):651-4. (http://www.ncbi.nlm.nih.gov/pubmed/9683616?dopt=Abstract)
- Rozet JM, Perrault I, Gerber S, Hanein S, Barbet F, Ducroq D, Souied E, Munnich A, Kaplan J. Complete abolition of the retinal-specific guanylyl cyclase (retGC-1) catalytic ability consistently leads to leber congenital amaurosis (LCA). Invest Ophthalmol Vis Sci. 2001 May;42(6):1190-2. (http://www.ncbi.nlm.nih.gov/pubmed/11328726?dopt=Abstract)
- Ugur Iseri SA, Durlu YK, Tolun A. A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis. Eur J Hum Genet. 2010 Oct;18(10):1121-6. doi: 10.1038/ejhg.2010.81. Epub 2010 Jun 2. (http://www.ncbi.nlm.nih.gov/pubmed/20517349?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.