ARHGEF gene family

The ARHGEF gene family provides instructions for making proteins known as Rho guanine nucleotide exchange factors (GEFs). Rho GEFs turn on proteins called Rho GTPases, which are molecular switches that regulate many essential processes within cells. Rho GTPases are turned off (inactivated) when they are attached (bound) to a molecule called GDP and are turned on (activated) when they are bound to another molecule called GTP. Rho GEFs remove GDP and attach GTP to Rho GTPases in order to activate them.

Active Rho GTPases bind to a variety of proteins (known as effectors) to regulate cellular processes including cell growth and division (proliferation), maturation (differentiation) of cells, cell movement, and progression of the cell through its replication cycle. Rho GTPases also play a role in regulating the first step in the production of proteins from genes (transcription) and the organization of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework.

Mutations in genes within the ARHGEF gene family can impair the function of Rho GEF proteins, which disrupts the activation of Rho GTPases. Abnormal overactivation or underactivation of Rho GTPases affects the regulation of their effectors and the cellular processes that they control, which can lead to a variety of disorders. Mutations in the Rho GEF gene ALS2 can cause amyotrophic lateral sclerosis, a condition characterized by progressive movement problems and muscle wasting. FGD1 gene mutations cause a developmental disorder known as Aarskog-Scott syndrome. Mutations in other ARHGEF genes are associated with intellectual disability or an increased risk of developing leukemia.