Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia-inducible factor-2alpha (HIF-2α)) is a protein that is encoded by the EPAS1 gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart. Mutation often leads to neuroendocrine tumors. The EPAS1 gene encodes one subunit of a transcription factor involved in the induction of genes regulated by oxygen, and which is induced as oxygen concentration falls (hypoxia). The protein contains a basic helix-loop-helix protein dimerization domain as well as a domain found in signal transduction proteins which respond to oxygen levels. EPAS1 is involved in the development of the embryonic heart and is expressed in endothelial cells that line the walls of blood vessels in the umbilical cord. EPAS1 is also essential for the maintenance of catecholamine homeostasis and protection against heart failure during early embryonic development. Catecholamines regulated by EPAS1 include epinephrine and norepinephrine. It is critical that the production of catecholamines remain in homeostatic conditions so that both the delicate fetal heart and the adult heart do not overexert themselves and induce heart failure. Catecholamine production in the embryo is related to control of cardiac output by increasing the fetal heart rate.