GNAT1

GNAT1 is a gene that encodes the alpha subunit of transducin (Gαt1), a member of the heterotrimeric G protein family. The protein functions in the vertebrate retina as part of the phototransduction cascade in rod photoreceptors, translating light into an electrical signal.

In darkness, transducin forms a complex with Gβ1γ1 and carries GDP. When photons strike rhodopsin, the receptor acts as a guanine nucleotide exchange factor, promoting the exchange of GDP for GTP on GNAT1α. The GTP-bound Gαt1 dissociates from Gβγ and activates phosphodiesterase-6 (PDE6), leading to hydrolysis of cGMP, closure of cGMP-gated ion channels, and hyperpolarization of the rod cell. After GTP hydrolysis, Gαt1 re-associates with Gβγ to reset the cascade.

GNAT1 is expressed mainly in the retina, with a predominant presence in rod photoreceptors, and is highly conserved across vertebrates. The protein comprises roughly 350 amino acids and contains the conserved GTPase domain characteristic of Gα subunits. It is closely related to other transducin alpha subunits, such as cone transducin GNAT2, which mediates phototransduction in cone cells.

Clinical relevance is mostly described in the context of rare inherited retinal disorders. Pathogenic variants in GNAT1 have been reported in association with retinal dystrophies and night vision impairment in some families, highlighting its essential role in normal phototransduction. Further studies continue to clarify the spectrum of GNAT1-related retinal diseases and underlying mechanisms.