EIF2AK4

EIF2AK4 Background

eIF-2-alpha kinase GCN2 is a protein in humans that is encoded by the EIF2AK4 gene. EIF2AK4 belongs to a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 to downregulate protein synthesis in response to varied cellular stresses. It is found in several tissues throughout the body, including blood vessel walls. The EIF2AK4 protein can activate another protein called eIF2 alpha (eIF2α), which helps control protein production. When cells are under stress, for example when the level of protein building blocks (amino acids) is too low, EIF2AK4 activates eIF2α. When turned on, eIF2α stimulates processes that reduce protein production, which helps conserve amino acids. In addition, activated eIF2α can trigger production of certain proteins called transcription factors, which control gene activity. The transcription factors regulated by eIF2α control the activity of genes involved in processes that help reduce the stress on the cell. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of pulmonary hypertension (PH), one of the rarest and deadliest diseases ^[1].

[1] Ossama K. Abou Hassan, Wiam Haidar, et al. Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension [J]. BMC Medical Genetics volume 20, Article number: 176 (2019).