ABCA4

About ABCA4

ABCA4 on chromosome 1p22.1 encodes an ATP binding cassette transporter located in the disc membranes of rod and cone outer segments. It helps clear retinal derivatives from the discs after light exposure, preventing them from forming toxic bisretinoid compounds. When ABCA4 function is reduced, these compounds accumulate in the retinal pigment epithelium as lipofuscin, damaging it and the overlying photoreceptors. Variants on both copies of ABCA4 cause Stargardt disease, the most common inherited macular dystrophy, as well as some cone rod dystrophies and forms of retinitis pigmentosa, with severity depending on how much residual function the variants allow. ABCA4 is a very large and highly variable gene, and many variants, including deep intronic ones, can be difficult to interpret. Drugs that slow vitamin A dimerization and gene therapy approaches are being investigated.