EPAS1 gene

The EPAS1 gene provides instructions for making a protein that helps the body adapt to changing oxygen levels.

Normal Function

The EPAS1 gene, often known as HIF2A, provides instructions for making a protein called hypoxia-inducible factor 2-alpha (HIF-2α). This protein is a subunit of a larger complex called HIF, which regulates genes involved in cell division, the formation of new blood vessels, and the production of red blood cells. It is the major regulator of the hormone erythropoietin.

When oxygen levels are low (hypoxia), HIF-2α is degraded more slowly, allowing more HIF to accumulate. This stimulates the formation of new blood vessels and red blood cells to maximize oxygen delivery. The EPAS1 gene is also involved in the body's adaptation to high-altitude environments where oxygen levels are lower.

Health Conditions Related to Genetic Changes

Familial erythrocytosis

At least five mutations in the EPAS1 gene have been found to cause familial erythrocytosis (specifically ECYT4), an inherited condition characterized by an increased number of red blood cells and an elevated risk of abnormal blood clots.

These mutations change single amino acids in the HIF-2α protein, preventing it from being degraded efficiently. As a result, HIF accumulates in cells even when oxygen levels are adequate. This leads to the unnecessary production of red blood cells, resulting in an excess of these cells in the bloodstream.