Rho-related BTB domain-containing protein 2 (RHOBTB2)

Rho-related BTB domain-containing protein 2 (RHOBTB2) is an atypical member of the Rho GTPase family, characterized structurally by a Rho-like GTPase domain at its N-terminus and two BTB (Broad-complex, Tramtrack, and Bric-à-brac) domains. Unlike typical Rho GTPases, RHOBTB2's BTB domains enable it to form homo- and heterodimers and interact with ubiquitin ligase scaffolding complexes, especially Cullin-3 (Cul3), targeting specific substrates for ubiquitin-mediated degradation in the proteasome[1][2][3][4]. RHOBTB2 is mainly expressed in neural tissue and acts as a tumor suppressor, frequently lost or silenced in multiple cancers, notably breast cancer, by mechanisms such as gene deletion or promoter hypermethylation[1][3][4]. Functionally, it contributes to the regulation of apoptosis, cell proliferation, cytoskeletal dynamics, and differentiation, with roles in both cancer suppression and neurodevelopment—germline or de novo coding variants cause severe pediatric epilepsy and developmental delay (DEE64)[1][3][4]. The molecule serves as a biomarker for cancer prognosis when its levels are reduced, and as a mechanistic diagnostic clue in specific epileptic encephalophenotypes due to its loss-of-function variants[4]. Currently, no approved drugs are known to directly target RHOBTB2.

Other names

DBC2KIAA0717Deleted in breast cancer 2 gene proteinp83DEE64EIEE64