RHOG Human

The Ras Homolog Gene Family Member G (RHOG) is a protein-coding gene that belongs to the Rho family of small GTPases. These proteins act as molecular switches in signal transduction pathways, cycling between inactive GDP-bound and active GTP-bound states. RHOG plays a crucial role in various cellular processes, including the reorganization of the actin cytoskeleton, cell shape, attachment, and motility .

The RHOG gene is located on chromosome 11 in humans and encodes a protein that is involved in the regulation of the actin cytoskeleton. The protein facilitates the translocation of a functional guanine nucleotide exchange factor (GEF) complex from the cytoplasm to the plasma membrane. This translocation activates the ras-related C3 botulinum toxin substrate 1, promoting lamellipodium formation and cell migration .

RHOG is a multifaceted member of the Rho family, sharing the highest sequence identity with the Rac subfamily members. It acts as a molecular switch and plays a central role in regulating fundamental processes in immune cells, such as actin-cytoskeleton dynamics, transendothelial migration, survival, and proliferation. RHOG is also involved in immunological functions like phagocytosis and trogocytosis during inflammatory responses .

RHOG regulates actin reorganization in lymphocytes, possibly through the modulation of Rac1 activity. It is required for the formation of membrane ruffles during macropinocytosis and plays a role in cell migration. RHOG is essential for the formation of cup-like structures during the trans-endothelial migration of leukocytes . The dynamic expression of different transcription factors, non-coding RNAs, and the spatiotemporal coordination of different GEFs with their downstream effector molecules regulate the cascade of Rho signaling in immune cells .

Alterations in RHOG-specific signaling can lead to physiological, pathological, and developmental adversities. Several mutations and RHOG-modulating factors are known to predispose the downstream signaling with abnormal gene expression linked to multiple diseases. Diseases associated with RHOG include Familial Hemophagocytic Lymphohistiocytosis 5 and Lymphoproliferative Syndrome, X-Linked, 2 .

The RHOG gene is a late-induced gene, and RNA accumulation is proportional to the strength of the mitogen used. Phylogenetic studies suggest that it may have diverged early during evolution .