Reviewed January 2010
What is the official name of the FGD4 gene?
The official name of this gene is “FYVE, RhoGEF and PH domain containing 4.”
FGD4 is the gene's official symbol. The FGD4 gene is also known by other names, listed below.
What is the normal function of the FGD4 gene?
The FGD4 gene provides instructions for making a protein called frabin. This protein plays an important role in the nervous system, where it helps regulate a type of cell signaling involved in myelin production. Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses. The formation of a protective myelin sheath around nerve cells is called myelination. Frabin is particularly important in the myelination of the peripheral nervous system, which connects the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.
Frabin is also believed to be involved in the organization of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move. Researchers believe that frabin plays a role in attaching the actin cytoskeleton to the cell membrane.
Does the FGD4 gene share characteristics with other genes?
The FGD4 gene belongs to a family of genes called ARHGEF (Rho guanine nucleotide exchange factors). It also belongs to a family of genes called ZFYVE (zinc fingers, FYVE-type).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the FGD4 gene related to health conditions?
- Charcot-Marie-Tooth disease - caused by mutations in the FGD4 gene
At least five mutations in the FGD4 gene have been identified in people with Charcot-Marie-Tooth disease type 4H. These mutations change the protein's shape or result in an abnormally short, nonfunctional protein. The disruption of frabin's role in cell signaling causes abnormal myelination of the peripheral nervous system, resulting in the signs and symptoms of Charcot-Marie-Tooth disease type 4H.
Where is the FGD4 gene located?
Cytogenetic Location: 12p11.21
Molecular Location on chromosome 12: base pairs 32,399,540 to 32,646,049
The FGD4 gene is located on the short (p) arm of chromosome 12 at position 11.21.
More precisely, the FGD4 gene is located from base pair 32,399,540 to base pair 32,646,049 on chromosome 12.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about FGD4?
You and your healthcare professional may find the following resources about FGD4 helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1468)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for FGD4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=121512%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28FGD4%5BTIAB%5D%29%20OR%20%28%28CMT4H%5BTIAB%5D%29%20OR%20%28FRABIN%5BTIAB%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/611104)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_FGD4.html)
- HGNC Gene Family: Pleckstrin homology (PH) domain containing (http://www.genenames.org/genefamilies/PLEKH)
- HGNC Gene Family: Rho guanine nucleotide exchange factors (http://www.genenames.org/genefamilies/ARHGEF)
- HGNC Gene Family: Zinc fingers, FYVE domain containing (http://www.genenames.org/genefamilies/ZFYVE)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=19125)
- Inherited Peripheral Neuropathies Mutation Database (http://www.molgen.ua.ac.be/CMTMutations/Mutations/Mutations.cfm?Context=41)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/121512)
What other names do people use for the FGD4 gene or gene products?
- actin-filament binding protein frabin
- FGD1 family, member 4
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding FGD4?
cell membrane ;
myelin sheath ;
nervous system ;
peripheral nervous system ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Delague V, Jacquier A, Hamadouche T, Poitelon Y, Baudot C, Boccaccio I, Chouery E, Chaouch M, Kassouri N, Jabbour R, Grid D, Mégarbané A, Haase G, Lévy N. Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. Am J Hum Genet. 2007 Jul;81(1):1-16. Epub 2007 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/17564959?dopt=Abstract)
- De Sandre-Giovannoli A, Delague V, Hamadouche T, Chaouch M, Krahn M, Boccaccio I, Maisonobe T, Chouery E, Jabbour R, Atweh S, Grid D, Mégarbané A, Lévy N. Homozygosity mapping of autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy (CMT4H) to a novel locus on chromosome 12p11.21-q13.11. J Med Genet. 2005 Mar;42(3):260-5. (http://www.ncbi.nlm.nih.gov/pubmed/15744041?dopt=Abstract)
- Fabrizi GM, Taioli F, Cavallaro T, Ferrari S, Bertolasi L, Casarotto M, Rizzuto N, Deconinck T, Timmerman V, De Jonghe P. Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. Neurology. 2009 Mar 31;72(13):1160-4. doi: 10.1212/01.wnl.0000345373.58618.b6. (http://www.ncbi.nlm.nih.gov/pubmed/19332693?dopt=Abstract)
- OMIM: FYVE, RhoGEF, AND PH DOMAIN-CONTAINING PROTEIN 4 (http://omim.org/entry/611104)
- Gene Review: Charcot-Marie-Tooth Neuropathy Type 4 (http://www.ncbi.nlm.nih.gov/books/NBK1468)
- Houlden H, Hammans S, Katifi H, Reilly MM. A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. Neurology. 2009 Feb 17;72(7):617-20. doi: 10.1212/01.wnl.0000342463.35089.cc. (http://www.ncbi.nlm.nih.gov/pubmed/19221294?dopt=Abstract)
- Ikeda W, Nakanishi H, Takekuni K, Itoh S, Takai Y. Identification of splicing variants of Frabin with partly different functions and tissue distribution. Biochem Biophys Res Commun. 2001 Sep 7;286(5):1066-72. (http://www.ncbi.nlm.nih.gov/pubmed/11527409?dopt=Abstract)
- Kim Y, Ikeda W, Nakanishi H, Tanaka Y, Takekuni K, Itoh S, Monden M, Takai Y. Association of frabin with specific actin and membrane structures. Genes Cells. 2002 Apr;7(4):413-20. (http://www.ncbi.nlm.nih.gov/pubmed/11952837?dopt=Abstract)
- Nakanishi H, Takai Y. Frabin and other related Cdc42-specific guanine nucleotide exchange factors couple the actin cytoskeleton with the plasma membrane. J Cell Mol Med. 2008 Aug;12(4):1169-76. doi: 10.1111/j.1582-4934.2008.00345.x. Epub 2008 Apr 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18410521?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/121512)
- Ono Y, Nakanishi H, Nishimura M, Kakizaki M, Takahashi K, Miyahara M, Satoh-Horikawa K, Mandai K, Takai Y. Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac. Oncogene. 2000 Jun 22;19(27):3050-8. (http://www.ncbi.nlm.nih.gov/pubmed/10871857?dopt=Abstract)
- 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, Krüttgen A, Rudnik-Schöneborn 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. Epub 2007 May 24. (http://www.ncbi.nlm.nih.gov/pubmed/17564972?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.