Rab3GAP2

Rab3GAP2 is a human gene that encodes the regulatory subunit of the Rab3 GTPase-activating protein (Rab3GAP) complex. The Rab3GAP complex consists of Rab3GAP1, the catalytic subunit, and Rab3GAP2, the non-catalytic regulatory subunit. Together, they act as a GTPase-activating protein for Rab3 family small GTPases, promoting the hydrolysis of GTP to GDP and thereby switching Rab3 from an active to an inactive state.

Through this cycle, the Rab3GAP complex regulates vesicle trafficking, docking, and regulated exocytosis, with important roles in neuronal and neurosecretory pathways. Rab3GAP2 contributes to the stability and substrate recognition of the complex and is involved in controlling Rab3 signaling at membranes such as the Golgi apparatus and synaptic vesicles.

Clinically, biallelic mutations in RAB3GAP2 have been linked to Warburg Micro syndrome, a severe autosomal recessive neurodevelopmental disorder. Features commonly include ocular anomalies (such as cataracts and optic nerve defects), microcephaly, brain malformations, and developmental impairment. The phenotype overlaps with disorders caused by dysfunction of the Rab3GAP machinery, including mutations in RAB3GAP1, reflecting the shared dependence on Rab3-mediated vesicle trafficking for normal neural development.

RAB3GAP2 interacts with Rab3GAP1 and Rab3 family members, forming a functional unit that coordinates Rab3 signaling. This protein is expressed in multiple tissues, with prominent relevance in the nervous system and secretory cells, where regulated exocytosis is essential.