FGD4
MIM.611104 12p11.2
FGD4, or Rho GDP/GTP exchange factor frabin, is a GDP/GTP exchange protein for CDC42 (MIM.116952) and shows actin filament (F-actin)-binding activity. FGD4 is a guanine nucleotide exchange factor (ARHGEF) for the Rho GTPase cell-division cycle 42 (Cdc42).
GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (ARHGEFs).
Pathology
germline mutations in Charcot-Marie-Tooth disease type 4H (MIM.609311)
- disruption of frabin/FGD4, causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy.
- frabin can induce Cdc42-mediated cell-shape changes in transfected Schwann cells
- Rho GTPase signaling is essential for proper myelination of the peripheral nervous system.
References
Stendel C, Roos A, Deconinck T, Pereira J, Castagner F, Niemann A, Kirschner J, Korinthenberg R, Ketelsen UP, Battaloglu E, Parman Y, Nicholson G, Ouvrier R, Seeger J, De Jonghe P, Weis J, Kruttgen A, Rudnik-Schoneborn S, Bergmann C, Suter U, Zerres K, Timmerman V, Relvas JB, Senderek J. Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4. Am J Hum Genet. 2007 Jul;81(1):158-64. PMID: #17564972#
Delague, V.; Jacquier, A.; Hamadouche, T.; Poitelon, Y.; Baudot, C.; Boccaccio, I.; Chouery, E.; Chaouch, M.; Kassouri, N.; Jabbour, R.; Grid, D.; Megarbane, A.; Haase, G.; Levy, N. : Mutations in FGD4 encoding the Rho GDP/GTP exchange factor frabin cause autosomal recessive Charcot-Marie-Tooth type 4H. Am. J. Hum. Genet. 81: 1-16, 2007. PubMed ID : #17564959#