RDH12

RDH12 is a human gene that encodes retinol dehydrogenase 12, an enzyme in the short-chain dehydrogenase/reductase (SDR) superfamily. The RDH12 enzyme participates in retinal vitamin A metabolism in the retina, a component of the visual cycle that recycles retinoids after phototransduction. It is expressed in the retina, particularly in photoreceptor cells and the retinal pigment epithelium, where it participates in NADPH-dependent reactions that interconvert retinaldehydes and retinols, contributing to the clearance of phototransduction–generated retinaldehyde.

Clinical significance of RDH12 mutations is highlighted by autosomal recessive retinal dystrophies. Pathogenic variants in RDH12 can cause Leber congenital amaurosis (LCA) and other forms of early-onset retinal dystrophy, with phenotypes ranging from severe congenital blindness to progressive rod-cone degeneration. A substantial number of disease-causing variants have been described, including missense, nonsense, and splice-site mutations, generally leading to reduced or absent enzyme activity and photoreceptor degeneration. RDH12 is a target of genetic testing in inherited retinal disease panels.

Genetics and molecular features: RDH12 is conserved across vertebrates and belongs to the SDR family, which is characterized by conserved motifs involved in catalysis and cofactor binding. The protein’s retinal metabolizing activity places RDH12 in the broader context of retinoid processing that supports the retina’s response to light and maintenance of photoreceptor health.