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URL of this page: https://medlineplus.gov/genetics/gene/gucy2d/

GUCY2D gene

guanylate cyclase 2D, retinal

Normal Function

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-sensing cells called photoreceptors. The retina contains two types of photoreceptors: 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. During phototransduction, light entering the eye triggers a series of chemical reactions that close the channels in photoreceptor cell membranes that are normally open in low-light conditions. This closure produces an electrical signal, which is then interpreted by the brain as vision. 

Once photoreceptors have been stimulated by light, they must return to their open (or "dark") state before they can be stimulated again. The GUCY2D protein is involved in a chemical reaction that re-opens the cell membrane channels and helps return photoreceptors to their dark state after light exposure.

Health Conditions Related to Genetic Changes

Cone-rod dystrophy

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the GUCY2D gene can cause a disorder called cone-rod dystrophy type 6. Cone-rod dystrophies are a group of eye disorders that affect the retina and cause vision loss that may worsen over time. Cone-rod dystrophy type 6 usually develops later in life and gradually affects central vision, color vision, and, eventually, night and peripheral vision.

Many of the pathogenic variants that cause cone-rod dystrophy type 6 affect a particular protein building block (amino acid) in the GUCY2D protein. Specifically, the amino acid arginine at position 838 is replaced with one of several other amino acids. This change in the GUCY2D protein impairs phototransduction, causing the photoreceptors to break down over time. The loss of these cells leads to the progressive vision loss that is characteristic of cone-rod dystrophy type 6. 

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Leber congenital amaurosis

Pathogenic variants in the GUCY2D gene can also cause Leber congenital amaurosis type 1. Leber congenital amaurosis is a group of eye disorders that affect the retina. People with Leber congenital amaurosis type 1 typically have severe vision loss that begins during infancy. Pathogenic variants in the GUCY2D gene account for 10 to 20 percent of all cases of Leber congenital amaurosis.

Many of the pathogenic variants in the GUCY2D gene that are associated with Leber congenital amaurosis type 1 cause cells to produce an abnormally short, nonfunctional version of the GUCY2D protein. Without this protein, photoreceptor cells cannot return to their dark state after they are exposed to light. This disrupts the process of phototransduction and leads to the severe visual impairment seen in children with Leber congenital amaurosis type 1.

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Autosomal recessive congenital stationary night blindness

MedlinePlus Genetics provides information about Autosomal recessive congenital stationary night blindness

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Other Names for This Gene

  • CYGD
  • LCA1
  • Leber congenital amaurosis 1
  • retGC
  • RETGC-1
  • retinal guanylate cyclase 1
  • rod outer segment membrane guanylate cyclase
  • ROS-GC
  • ROS-GC1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Boulanger-Scemama E, El Shamieh S, Demontant V, Condroyer C, Antonio A, Michiels C, Boyard F, Saraiva JP, Letexier M, Souied E, Mohand-Said S, Sahel JA, Zeitz C, Audo I. Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation. Orphanet J Rare Dis. 2015 Jun 24;10:85. doi: 10.1186/s13023-015-0300-3. Citation on PubMed or Free article on PubMed Central
  • Boye SE. Leber congenital amaurosis caused by mutations in GUCY2D. Cold Spring Harb Perspect Med. 2014 Sep 25;5(1):a017350. doi: 10.1101/cshperspect.a017350. Citation on PubMed
  • 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. doi: 10.1002/humu.9067. Citation on PubMed
  • 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. doi: 10.1007/s10384-003-0050-y. Citation on PubMed
  • Kitiratschky VB, Wilke R, Renner AB, Kellner U, Vadala 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. Citation on PubMed
  • Kumaran N, Pennesi ME, Yang P, Trzupek KM, Michaelides M. Nonsyndromic Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview. 2018 Oct 4 [updated 2025 Dec 4]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK531510/ Citation on PubMed
  • 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. doi: 10.1136/jmg.38.9.611. No abstract available. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • Stunkel ML, Brodie SE, Cideciyan AV, Pfeifer WL, Kennedy EL, Stone EM, Jacobson SG, Drack AV. Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D. Am J Ophthalmol. 2018 Jun;190:58-68. doi: 10.1016/j.ajo.2018.03.021. Epub 2018 Mar 17. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.