MRAP gene

melanocortin 2 receptor accessory protein

The MRAP gene provides instructions for making a protein called melanocortin-2 receptor accessory protein (MRAP). This protein transports another protein, called the melanocortin-2 receptor (or more commonly the adrenocorticotropic hormone [ACTH] receptor), from the interior of the cell to the cell surface. Specifically, the MRAP protein transports the ACTH receptor from a cell structure called the endoplasmic reticulum (ER), which is involved in protein processing and transport, to the cell membrane so that the receptor can function. The MRAP protein is also needed to turn on (activate) the ACTH receptor.

At the cell membrane, the activated ACTH receptor attaches (binds) to ACTH, which triggers the production of 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.

At least 13 mutations in the MRAP 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). MRAP gene mutations account for approximately 20 percent of cases of this condition. Most of these mutations lead to the production of a protein that cannot interact with the ACTH receptor and so is unable to transport it out of the ER to the cell membrane. As a result, the ACTH receptor is not at the cell surface where it is needed to 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.

Cytogenetic Location: 21q22.11, which is the long (q) arm of chromosome 21 at position 22.11

Molecular Location: base pairs 32,291,813 to 32,314,784 on chromosome 21 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 21q22.11, which is the long (q) arm of chromosome 21 at position 22.11
  • B27
  • C21orf61
  • FALP
  • fat cell-specific low molecular weight protein
  • fat tissue-specific low MW protein
  • GCCD2
  • melanocortin-2 receptor accessory protein