Normal Function
The ABCA4 gene provides instructions for making a protein that is found in the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, the ABCA4 protein is produced in the retina's light-sensing cells (photoreceptors). The ABCA4 protein transports potentially toxic substances that can damage photoreceptors. These substances form after phototransduction, the process by which light entering the eye is converted into electrical signals that are transmitted to the brain. The ABCA4 protein removes one of these substances, called N-retinylidene-PE, from photoreceptors.
Health Conditions Related to Genetic Changes
Cone-rod dystrophy
Many variants (also called mutations) in the ABCA4 gene have been found to cause a vision disorder called cone-rod dystrophy. The problems associated with this condition include a loss of visual sharpness (acuity), an increased sensitivity to light (photophobia), and impaired color vision. These vision problems worsen over time. It is estimated that ABCA4 gene variants account for 30 to 60 percent of cases of cone-rod dystrophy that are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder.
Most of the ABCA4 gene variants that cause cone-rod dystrophy change single protein building blocks (amino acids) in the ABCA4 protein. The altered protein cannot remove N-retinylidene-PE from photoreceptors. As a result, N-retinylidene-PE combines with another substance to produce a molecule called N-retinylidene-N-retinylethanolamine (A2E), which builds up in these cells. The buildup of A2E is toxic to photoreceptors and leads to their deterioration, causing progressive vision loss in people with cone-rod dystrophy. Cone-rod dystrophy caused by ABCA4 gene variants tends to be associated with more severe vision problems than cone-rod dystrophy caused by other genetic variants.
More About This Health ConditionStargardt macular degeneration
More than 1,000 variants in the ABCA4 gene have been found to cause Stargardt macular degeneration. Variants in this gene are the most common cause of this eye disease. Stargardt macular degeneration is characterized by vision loss that worsens over time.
Most of these variants change amino acids in the ABCA4 protein. A malfunctioning ABCA4 protein cannot remove N-retinylidene-PE from photoreceptors. As a result, N-retinylidene-PE combines with another substance to produce a fatty yellow pigment called lipofuscin, which builds up in retinal cells. The buildup of lipofuscin is toxic to the cells of the retina and causes progressive vision loss in people with Stargardt macular degeneration.
More About This Health ConditionAge-related macular degeneration
MedlinePlus Genetics provides information about Age-related macular degeneration
More About This Health ConditionRetinitis pigmentosa
MedlinePlus Genetics provides information about Retinitis pigmentosa
More About This Health ConditionOther Names for This Gene
- ABCA4_HUMAN
- ABCR
- ATP-binding cassette sub-family A member 4
- ATP-binding cassette transporter, retinal-specific
- ATP-binding cassette, sub-family A (ABC1), member 4
- photoreceptor rim protein
- retina-specific ABC transporter
- retinal-specific ATP-binding cassette transporter
- RIM ABC transporter
- RIM protein
- RMP
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Molday RS, Zhang K. Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res. 2010 Oct;49(4):476-92. doi: 10.1016/j.plipres.2010.07.002. Epub 2010 Jul 13. Citation on PubMed or Free article on PubMed Central
- Molday RS, Zhong M, Quazi F. The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration. Biochim Biophys Acta. 2009 Jul;1791(7):573-83. doi: 10.1016/j.bbalip.2009.02.004. Epub 2009 Feb 20. Citation on PubMed or Free article on PubMed Central
- Thiadens AA, Phan TM, Zekveld-Vroon RC, Leroy BP, van den Born LI, Hoyng CB, Klaver CC; Writing Committee for the Cone Disorders Study Group Consortium; Roosing S, Pott JW, van Schooneveld MJ, van Moll-Ramirez N, van Genderen MM, Boon CJ, den Hollander AI, Bergen AA, De Baere E, Cremers FP, Lotery AJ. Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy. Ophthalmology. 2012 Apr;119(4):819-26. doi: 10.1016/j.ophtha.2011.10.011. Epub 2012 Jan 20. Citation on PubMed
- Tsybovsky Y, Molday RS, Palczewski K. The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Adv Exp Med Biol. 2010;703:105-25. doi: 10.1007/978-1-4419-5635-4_8. Citation on PubMed or Free article on PubMed Central
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