RhoA GTPase Y42C mutant (RHOA Y42C)

RhoA GTPase Y42C mutant is a single amino acid variant (tyrosine 42 to cysteine) of the small GTPase RhoA, a key regulator of actin cytoskeleton dynamics and cell signaling. The Y42C mutation is a recurrent, gain-of-function mutation found in diffuse-type gastric cancer and some other tumor types[1][2][3][7]. Biologically, this mutant engages effector pathways such as FAK, YAP/TAZ, and PI3K/AKT, promoting cytoskeletal rearrangements, cell proliferation, and migration[2]. Unlike classic RhoA activating mutations, Y42C alters effector specificity, sometimes causing both increased motility and enhanced oncogenic transformation[1][2]. Research indicates the mutant’s effects are not solely due to increased GTP loading, but also changes in effector association and downstream signaling. The pathogenicity of the RHOA Y42C mutation has stimulated the search for specific covalent inhibitors, which are in preclinical development[5][6]. No clinically approved drugs currently target RHOA Y42C specifically; it is mainly a subject of ongoing translational research. The mutation is considered a potential biomarker and therapeutic target in oncology, particularly for diffuse type gastric cancer[2][3][6].

Other names

RhoA Y42CRHOA p.Tyr42CysRHOA tyrosine 42 to cysteine mutant

Covalent inhibition of RhoA Y42C GTPase activity (experimental)[6]; Disruption of RhoA-effector binding and downstream signal transduction