GUCY1A2

GUCY1A2 is a protein-coding gene in humans that encodes the alpha-2 catalytic subunit of soluble guanylate cyclase (sGC). In sGC, an alpha subunit (including GUCY1A2) forms a heterodimer with a beta subunit (GUCY1B1) to create the NO-sensitive enzyme. When nitric oxide (NO) binds to the heme moiety on the beta subunit, the enzyme catalyzes the conversion of guanosine triphosphate (GTP) to cyclic GMP (cGMP). The rise in cGMP activates downstream effectors, notably protein kinase G (PKG), and modulates processes such as vascular smooth muscle relaxation, inhibition of platelet aggregation, and various aspects of neurotransmission.

Expression of GUCY1A2 has been detected in multiple tissues, reflecting its role in diverse NO–cGMP signaling pathways. It is one of several alpha subunits that assemble with beta subunits to form functional sGC; tissue-specific expression patterns contribute to variation in NO signaling across organs. sGC activity can be influenced by NO availability as well as by pharmacological stimulators and activators studied in research and clinical settings.

Clinically, NO–sGC–cGMP signaling is central to cardiovascular physiology. Dysregulation of this pathway is associated with conditions such as hypertension, heart failure, and pulmonary arterial hypertension, and sGC stimulators are used therapeutically for certain forms of PAH. Genetic variation in GUCY1A2 has been investigated for associations with cardiovascular traits, but a definitive causal role for GUCY1A2 mutations in human disease has not been established.

GUCY1A2 belongs to the guanylate cyclase family, which includes other alpha subunits (GUCY1A1, GUCY1A3) and the beta subunit (GUCY1B1) that together form functional sGC heterodimers. The gene is conserved across mammals and contributes to NO-responsive cGMP signaling.