MKRN3 gene

The MKRN3 gene provides instructions for making a protein that plays a critical role in regulating the timing of puberty.

Normal Function

The MKRN3 gene provides instructions for making a protein called makorin ring finger protein 3 (MKRN3). This protein plays a role in directing the onset of puberty, the process of sexual development that normally occurs in adolescence. Puberty begins when a gland in the brain called the hypothalamus is stimulated to release bursts of a hormone called gonadotropin releasing hormone (GnRH), which triggers the release of other hormones that direct sexual development. Research suggests that the MKRN3 protein inhibits the release of GnRH from the hypothalamus, effectively delaying the onset of puberty.

While the exact function of the MKRN3 protein is unknown, its structure suggests it plays a role in the ubiquitin-proteasome system, the cell machinery that breaks down unwanted proteins. MKRN3 is thought to help attach a molecule called ubiquitin to unwanted proteins, signaling the cell to break them down. Researchers speculate that MKRN3 adds ubiquitin to proteins that would otherwise stimulate GnRH release, ensuring that puberty does not begin until the appropriate time.

The activity of the MKRN3 gene is subject to genomic imprinting, a phenomenon where gene activation depends on which parent the gene was inherited from. In this case, only the copy inherited from the father is active; the copy inherited from the mother is inactive.

Health Conditions Related to Genetic Changes

Central precocious puberty

More than 20 MKRN3 gene mutations have been identified as causes of central precocious puberty. Individuals with this condition exhibit signs of puberty earlier than normal—before age 8 in girls and before age 9 in boys. These signs include:

• Development of breasts and the start of a menstrual period in girls
• Enlargement of the testes and penis in boys
• Development of pubic hair and a growth spurt in both girls and boys

Mutations in the MKRN3 gene are thought to lead to the production of a nonfunctional protein. Because the copy of the gene inherited from the mother is naturally inactive, affected individuals produce no functional MKRN3 protein. Without this protein to inhibit GnRH release, the hypothalamus releases hormone bursts prematurely, triggering early puberty. Because only the paternal copy of the gene is active, this condition can only be inherited from a person's father.

Other Names for This Gene

• CPPB2
• D15S9
• MGC88288
• probable E3 ubiquitin-protein ligase makorin-3
• RING finger protein 63
• RNF63
• ZFP127
• zinc finger protein 127
• ZNF127