EIF2AK3

EIF2AK3, also known as Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3, is a gene that encodes a protein kinase. This protein is a component of the endoplasmic reticulum stress response pathway. When the endoplasmic reticulum experiences stress, such as an accumulation of unfolded proteins, EIF2AK3 becomes activated.

Upon activation, EIF2AK3 phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α). This phosphorylation event leads to a global decrease in protein synthesis, which helps to reduce the load on the stressed endoplasmic reticulum. However, this shutdown is not absolute; the synthesis of certain stress-response proteins, including the transcription factor ATF4, is preferentially maintained. ATF4 then promotes the expression of genes involved in alleviating endoplasmic reticulum stress, promoting cell survival, or initiating apoptosis if the stress is irreparable.

Mutations in the EIF2AK3 gene have been linked to a rare genetic disorder called Gandavi disorder or severe infantile liver failure syndrome 1. This condition is characterized by progressive liver failure, developmental delay, and other severe health problems. The specific mutations impair the function of the EIF2AK3 protein, disrupting the endoplasmic reticulum stress response and leading to the observed clinical manifestations. Research into EIF2AK3 continues to shed light on the intricate mechanisms of protein homeostasis and cellular adaptation to stress.