POMC gene

The POMC gene (POMC stands for: Proopiomelanocortin) is a protein-coding gene located on chromosome 2p23.3. Alternatively spliced transcript variants encoding the same protein have been described.

The POMC gene encodes a preprotein that undergoes extensive, tissue-specific, post-translational processing and cleavage by subtilisin-like enzymes known as prohormone convertases. There are eight potential cleavage sites within the preprotein and, depending on the tissue type and the convertases available, up to ten biologically active peptides can be generated during processing, which are involved in various cellular functions.

• Corticotropin: Stimulates the adrenal glands to release cortisol ( COLI_HUMAN,P01189 )
• Melanocyte-stimulating hormone alpha/alpha-MSH: Anorexigenic peptide. Enhances skin pigmentation by increasing melanin production in melanocytes.
• Melanocyte-stimulating hormone beta/beta-MSH: Increases the pigmentation of the skin by increasing melanin production in the melanocytes.
• Beta-endorphin: Endogenous orexigenic opiate.
• Met-enkephalin: Endogenous opiate.

The encoded protein is mainly synthesized in the corticotropic cells of the anterior pituitary, where four cleavage sites are utilized:

• adrenocorticotropin, which is essential for normal steroidogenesis and the maintenance of normal adrenal gland weight

and

• lipotropin beta

are the main end products. In other tissues, including the hypothalamus, placenta and epithelium, all cleavage sites can be utilized, resulting in peptides that play a role in pain and energy homeostasis, melanocyte stimulation and immunomodulation. These include several different melanotropins, lipotropins and endorphins, which are contained in the peptides adrenocorticotropin and beta-lipotropin.

The antimicrobial melanotropin alpha peptide has an antibacterial and antifungal effect. Mutations in this gene have been linked to early onset obesity, adrenal insufficiency and red hair pigmentation.

Diseases associated with POMC include proopiomelanocortin deficiency, also known as OBAIRH, a rare, monogenic, autosomal recessive endocrine disorder characterized by early-onset obesity due to severe hyperphagia, pigmentary abnormalities, especially pale skin and red hair, and secondary hypocortisolism. The disorder results from a mutation in the POMC gene.

1. Graves LE et al. (2021) Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases. J Paediatr Child Health 57:484-490.
2. Jenks BG (2009) Regulation of proopiomelanocortin gene expression: an overview of the signaling cascades, transcription factors, and responsive elements involved. Ann N Y Acad Sci 1163:17-30.