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PROK2 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PROK2 gene

The PROK2 gene provides instructions for making the prokineticin 2 protein, which is vital for olfactory development, reproductive hormone regulation, and circadian rhythm coordination.

Normal Function

The PROK2 gene provides instructions for making a protein called prokineticin 2. This protein interacts with another protein called prokineticin receptor 2 (produced from the PROKR2 gene). On the cell surface, prokineticin 2 attaches (binds) 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. Prokineticin 2 and its receptor are produced in many organs and tissues, including the small intestine, certain regions of the brain, and several hormone-producing (endocrine) tissues.

Prokineticin 2 and its receptor play a role in the development of a group of nerve cells that are specialized to process smells (olfactory neurons). These neurons move (migrate) from the developing nose to a structure in the front of the brain called the olfactory bulb, which is critical for the perception of odors. Prokineticin 2 and its receptor are also involved in the migration of nerve cells that produce gonadotropin-releasing hormone (GnRH). GnRH controls the production of several hormones that direct sexual development before birth and during puberty. These hormones are also important for the normal function of the ovaries in women and the testes in men.

Several additional functions of prokineticin 2 and its receptor have been discovered. 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.

Health Conditions Related to Genetic Changes

Kallmann syndrome

At least 16 mutations in the PROK2 gene have been identified in people with Kallmann syndrome, a disorder characterized by the combination of hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) and an impaired sense of smell. Researchers estimate that mutations in the PROK2 and PROKR2 genes together account for about 9 percent of all cases of Kallmann syndrome.

Most of the PROK2 gene mutations that cause Kallmann syndrome change single protein building blocks (amino acids) in prokineticin 2. These mutations disrupt the protein's activity, affecting its ability to bind to its receptor to send signals normally. Studies suggest that a loss of this signaling disrupts the migration and survival of olfactory neurons and GnRH-producing neurons in the developing brain. If olfactory nerve cells do not extend to the olfactory bulb, a person's sense of smell will be impaired or absent. Misplacement or premature loss of GnRH-producing neurons prevents the production of sex hormones, which interferes with normal sexual development and causes puberty to be delayed or absent.

Other Names for This Gene

  • BV8
  • KAL4
  • MIT1
  • PK2
  • PROK2_HUMAN
  • Protein Bv8 homolog

Frequently Asked Questions

While both genes are part of the same signaling pathway, PROK2 produces the prokineticin 2 protein, which acts as the signaling molecule, whereas PROKR2 produces the receptor that receives this signal. Mutations in either gene can lead to similar clinical outcomes, such as anosmia and hypogonadotropic hypogonadism, because the interaction between the two proteins is required for proper neuronal migration.
It is possible for some individuals with PROK2 mutations to have a milder phenotype where the sense of smell is partially preserved but reproductive issues are present. However, the most common presentation involves significant or complete loss of smell. The severity of symptoms can vary depending on the specific mutation and whether it affects the protein's ability to bind to the receptor or its stability.
Diagnosis usually begins with clinical evaluation for anosmia and delayed puberty, followed by hormonal blood tests to check levels of GnRH, LH, FSH, and sex hormones. Genetic testing, specifically sequencing of the PROK2 gene, is required to confirm the diagnosis. If PROK2 testing is negative, clinicians often test the PROKR2 gene as well, since mutations in either gene can cause the same syndrome.
Yes, PROK2 mutations often lead to infertility due to the lack of sex hormone production. However, fertility can often be achieved through hormone replacement therapy. For women, this may involve estrogen and progesterone therapy, while for men, it may involve testosterone or gonadotropin injections to stimulate sperm production. These treatments manage the symptoms but do not correct the underlying genetic mutation.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.