ARHGEF11 Gene - Function, Mutations, and Disease Associations

ARHGEF11 encodes a Rho guanine nucleotide exchange factor (GEF) that activates Rho GTPases, particularly RhoA, by catalyzing the exchange of GDP for GTP. The protein contains a PDZ domain, a regulator of G protein signaling (RGS) domain, and a Dbl homology (DH) domain. It is highly expressed in the brain and plays critical roles in neuronal development, axon guidance, and synaptic plasticity. Mutations in ARHGEF11 are associated with hereditary spastic paraplegia and have been implicated in glioma and other cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• RhoA signaling pathway

• Axon guidance

• G protein-coupled receptor signaling

• Regulation of actin cytoskeleton

ARHGEF11 (PDZ-RhoGEF) is a 1522-amino acid protein that localizes to the cytoplasm and plasma membrane. It contains a PDZ domain for protein-protein interactions, an RGS domain that modulates G protein signaling, and a tandem DH-PH domain responsible for RhoA exchange activity. The protein is essential for RhoA-mediated cytoskeletal remodeling, cell adhesion, and migration. In the nervous system, it regulates dendritic spine morphology and axonal outgrowth. Dysregulation of ARHGEF11 contributes to neurodegenerative diseases and cancer progression.