The GSK3B gene encodes for the protein serine-threonine kinase, which belongs to the glycogen synthase kinase subfamily which is expressed abundantly in the central nervous system and has been implicated in several neuropsychiatric disorders, including bipolar and major depressive disorder. It is an important target protein of several anti-depressants, including lithium, and upregulation of GSK3B is associated with an increased risk for mood disorders. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson's disease and Alzheimer's disease.
is inhibited by several hormones such as insulin, endothelial growth factor, and platelet-derived growth factor. Insulin inactivates it by phosphorylation of the specific serine residues Ser21 and Ser9 in GSK-3 isoforms α and β, respectively.
Individuals carrying this combination of gene variations on GSK3B have been linked with an increased susceptibility for mood disorders including depressive disorder, as well as an earlier age of onset for depressive disorder:
rs334555 C>G, rs11925868 A>C, rs11927974 G>A