PROK2

The PROK2 gene provides instructions for making a protein called prokineticin 2. This protein interacts with a protein called prokineticin receptor 2 (produced from the PROKR2 gene). On the cell surface, prokineticin 2 attaches to the receptor like a key in a lock. When the two proteins are connected, they trigger a series of chemical signals within the cell that regulate various cell functions.

In animal studies, prokineticin 2 and its receptor have been shown to play a role in the normal development of the olfactory bulb, which is a group of nerve cells in the brain that process smell. Research in animals has also suggested that prokineticin 2 and its receptor are involved in the movement (migration) of nerve cells that produce gonadotropin-releasing hormone (GnRH). GnRH controls the production of several other hormones that direct sexual development before birth and during puberty. These hormones are also important for the normal function of the gonads (ovaries in women and testes in men).

Several additional functions of prokineticin 2 and its receptor have been discovered in studies with animals. These proteins help stimulate the movement of food through the intestine and are likely involved in the formation of new blood vessels (angiogenesis). They also play a role in coordinating daily (circadian) rhythms, such as the sleep-wake cycle and regular changes in body temperature. Prokineticin 2 and its receptor are active in a region of the brain called the suprachiasmatic nucleus (SCN), which acts as an internal clock that controls circadian rhythms.

Little is known about the functions of prokineticin 2 and its receptor in humans. These proteins are produced in many organs and tissues, including the small intestine, certain regions of the brain, and several hormone-producing (endocrine) tissues. Researchers believe that the functions of these proteins in humans may be similar to their functions in other animals.

Kallmann syndrome - caused by mutations in the PROK2 gene

At least five mutations in the PROK2 gene have been identified in people with Kallmann syndrome type 4. Some of these mutations change single protein building blocks (amino acids) in prokineticin 2, while other mutations result in the production of an abnormally short version of the protein or prevent any functional protein from being made. These mutations disrupt the activity of prokineticin 2, but it is unclear how the genetic changes lead to the characteristic features of Kallmann syndrome. Researchers speculate that two PROK2 mutations, or a mutation in PROK2 combined with a mutation in another gene, may be necessary to cause the disorder.

Based on studies in animals, researchers suspect that the altered prokineticin 2 is unable to direct the migration of olfactory nerve cells and GnRH-producing nerve cells to their usual locations in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired. Misplacement of GnRH-producing neurons prevents the production of certain sex hormones, which interferes with normal sexual development and causes puberty to be delayed or absent.

Because the features of Kallmann syndrome vary among individuals, researchers believe that additional genetic and environmental factors may be involved.