familial glucocorticoid deficiency More than 40 mutations in the MC2R gene have been found to cause familial glucocorticoid deficiency. This condition is characterized by potentially life-threatening low blood sugar (hypoglycemia), recurrent infections, and skin coloring darker than that of other family members (hyperpigmentation). MC2R gene mutations account for approximately 25 percent of cases of this condition. Most of these mutations change single protein building blocks (amino acids) in the ACTH receptor. As a result, the receptor cannot be transported to the cell membrane or bind to ACTH . Without the binding of the ACTH receptor to its hormone, there is no signal to trigger the adrenal glands to produce glucocorticoids. A shortage of these hormones impairs blood sugar regulation, immune system function, and other cellular functions, leading to the signs and symptoms of familial glucocorticoid deficiency. primary macronodular adrenal hyperplasia Genetics Home Reference provides information about primary macronodular adrenal hyperplasia.

     The MC2R gene provides instructions for making a protein called adrenocorticotropic hormone (ACTH) receptor. This protein is found primarily in the adrenal glands, which are hormone-producing glands located on top of each kidney. The ACTH receptor is embedded in the membrane of cells where it attaches (binds) to ACTH . ACTH is a hormone that is released by the pituitary gland, located at the base of the brain. The binding of ACTH to its receptor triggers the adrenal glands to produce a group of hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body. The ACTH receptor also likely plays a role in the development of the adrenal glands before birth.

The following transcription factors affect gene expression:

• GR
• GR-alpha
• GR-beta
• CREB
• AP-1
• c-Jun
• deltaCREB
• c-Myc
• c-Fos

Tissue specificity:

Melanocytes and corticoadrenal tissue.

Molecular Function:

• Melanocortin Receptor Activity
• Corticotropin Receptor Activity

Biological Processes:

• Placenta Development
• G-Protein Coupled Receptor Signaling Pathway
• G-Protein Coupled Receptor Signaling Pathway, Coupled To Cyclic Nucleotide Second Messenger
• Positive Regulation Of Camp Biosynthetic Process

Drug Bank:

• Corticotropin
• Cosyntropin