The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. GR is composed of several conserved structural elements, including a carboxy-terminal ligand-binding domain, a neighboring hinge region containing nuclear localization signals, a central zinc-finger-containing DNA-binding domain, and an amino-terminal variable region that participates in ligand-independent gene transcription. GR has also been shown to be the limiting factor in the induction of gene expression by glucocorticoids. More importantly, mutant GRs lacking the signaling domain remain constitutively active.