FYVE, RhoGEF and PH domain-containing protein 4 (FGD4)

FYVE, RhoGEF and PH domain-containing protein 4 (FGD4, commonly known as frabin) is a guanine nucleotide exchange factor (GEF) specific for the Rho GTPase CDC42, involved in the regulation of actin cytoskeleton organization and cell shape[1][6][8]. The protein contains several domains including an F-actin-binding (FAB) domain, Dbl homology (DH) domain, two pleckstrin homology (PH) domains, and a FYVE zinc finger domain, enabling it to scaffold signaling molecules and interact with the cytoskeleton[2]. FGD4 is essential for Schwann cell function and myelination in peripheral nerves, and mutations cause Charcot-Marie-Tooth disease type 4H, a severe demyelinating neuropathy[2][4]. It also regulates CDC42-mediated events related to cellular invasion and endocytosis, and participates in complex signaling networks controlling structural and functional homeostasis of peripheral nerves[1][2][4]. There are no known therapeutic drugs directly targeting FGD4 as of current research[2][4].

Other names

FrabinZinc finger FYVE domain-containing protein 6CMT4H (Charcot-Marie-Tooth disease type 4H protein)FGD1-related F-actin-binding proteinActin filament-binding protein frabinZFYVE6FRABP

Catalyzes GDP-GTP exchange on CDC42, activating it, which in turn regulates downstream cytoskeletal and signaling pathways[1][6][8].