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FGD1 gene

FYVE, RhoGEF and PH domain containing 1

Normal Function

The FGD1 gene provides instructions for making a protein that functions as a guanine nucleotide exchange factor (GEF). GEFs turn on (activate) proteins called GTPases, which play an important role in chemical signaling within cells. GTPases are turned off (inactivated) when they are attached (bound) to a molecule called GDP and are turned on (activated) when they are bound to another molecule called GTP.

The FGD1 protein activates the GTPase known as Cdc42 by stimulating the exchange of GDP for GTP. Once Cdc42 is active, it transmits signals that are critical for various aspects of development before and after birth, particularly the development of bones. The FGD1 protein may also be involved in maintenance (remodeling) of the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Through this process, the protein appears to play a role in cell movement (migration) and the remodeling of blood vessels.

Health Conditions Related to Genetic Changes

Aarskog-Scott syndrome

More than 40 variants (also known as mutations) in the FGD1 gene have been found to cause Aarskog-Scott syndrome, a rare condition that occurs primarily in males. Affected boys typically have distinctive facial features, genital abnormalities, childhood short stature, and other skeletal abnormalities. The FGD1 gene variants lead to the production of an abnormally functioning FGD1 protein, which disrupts Cdc42 signaling. Altering the transmission of Cdc42 signals likely impairs normal development of bones and other tissues, resulting in the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.

More About This Health Condition

Other Names for This Gene

  • AAS
  • faciogenital dysplasia protein
  • FGDY
  • ZFYVE3

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases


  • Daubon T, Buccione R, Genot E. The Aarskog-Scott syndrome protein Fgd1 regulates podosome formation and extracellular matrix remodeling in transforming growth factor beta-stimulated aortic endothelial cells. Mol Cell Biol. 2011 Nov;31(22):4430-41. doi: 10.1128/MCB.05474-11. Epub 2011 Sep 12. Citation on PubMed or Free article on PubMed Central
  • Estrada L, Caron E, Gorski JL. Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. Hum Mol Genet. 2001 Mar 1;10(5):485-95. doi: 10.1093/hmg/10.5.485. Citation on PubMed
  • Gao L, Gorski JL, Chen CS. The Cdc42 guanine nucleotide exchange factor FGD1 regulates osteogenesis in human mesenchymal stem cells. Am J Pathol. 2011 Mar;178(3):969-74. doi: 10.1016/j.ajpath.2010.11.051. Citation on PubMed or Free article on PubMed Central
  • Genot E, Daubon T, Sorrentino V, Buccione R. FGD1 as a central regulator of extracellular matrix remodelling--lessons from faciogenital dysplasia. J Cell Sci. 2012 Jul 15;125(Pt 14):3265-70. doi: 10.1242/jcs.093419. Epub 2012 Aug 1. Citation on PubMed
  • Gorski JL, Estrada L, Hu C, Liu Z. Skeletal-specific expression of Fgd1 during bone formation and skeletal defects in faciogenital dysplasia (FGDY; Aarskog syndrome). Dev Dyn. 2000 Aug;218(4):573-86. doi: 10.1002/1097-0177(2000)9999:99993.0.CO;2-F. Citation on PubMed
  • Hou P, Estrada L, Kinley AW, Parsons JT, Vojtek AB, Gorski JL. Fgd1, the Cdc42 GEF responsible for Faciogenital Dysplasia, directly interacts with cortactin and mAbp1 to modulate cell shape. Hum Mol Genet. 2003 Aug 15;12(16):1981-93. doi: 10.1093/hmg/ddg209. Citation on PubMed
  • Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E, Rinaldi MM, Medeira A, Sorrentino V. Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. Eur J Hum Genet. 2004 Jan;12(1):16-23. doi: 10.1038/sj.ejhg.5201081. Citation on PubMed
  • Oshima T, Fujino T, Ando K, Hayakawa M. Role of FGD1, a Cdc42 guanine nucleotide exchange factor, in epidermal growth factor-stimulated c-Jun NH2-terminal kinase activation and cell migration. Biol Pharm Bull. 2011;34(1):54-60. doi: 10.1248/bpb.34.54. Citation on PubMed
  • Pedigo NG, Van Delden D, Walters L, Farrell CL. Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease. Physiol Genomics. 2016 Jul 1;48(7):446-54. doi: 10.1152/physiolgenomics.00101.2015. Epub 2016 May 6. Citation on PubMed

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