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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

ARHGEF gene family

Reviewed August 2012

What are the ARHGEF genes?

The ARHGEF gene family provides instructions for making proteins known as Rho guanine nucleotide exchange factors (GEFs). Rho GEFs turn on proteins called Rho GTPases, which are molecular switches that regulate many essential processes within cells. Rho 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. Rho GEFs remove GDP and attach GTP to Rho GTPases in order to activate them.

Active Rho GTPases bind to a variety of proteins (known as effectors) to regulate cellular processes including cell growth and division (proliferation), maturation (differentiation) of cells, cell movement, and progression of the cell through its replication cycle. Rho GTPases also play a role in regulating the first step in the production of proteins from genes (transcription) and the organization of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework.

Mutations in genes within the ARHGEF gene family can impair the function of Rho GEF proteins, which disrupts the activation of Rho GTPases. Abnormal overactivation or underactivation of Rho GTPases affects the regulation of their effectors and the cellular processes that they control, which can lead to a variety of disorders. Mutations in the Rho GEF gene ALS2 can cause amyotrophic lateral sclerosis, a condition characterized by progressive movement problems and muscle wasting. FGD1 gene mutations cause a developmental disorder known as Aarskog-Scott syndrome. Mutations in other ARHGEF genes are associated with intellectual disability or an increased risk of developing leukemia.

Which genes are included in the ARHGEF gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides an index of gene families ( and their member genes.

Genetics Home Reference summarizes the normal function and health implications of these members of the ARHGEF gene family: ALS2, FGD1, FGD4, and SOS1.

What conditions are related to genes in the ARHGEF gene family?

Genetics Home Reference includes these conditions related to genes in the ARHGEF gene family:

  • Aarskog-Scott syndrome
  • amyotrophic lateral sclerosis
  • Charcot-Marie-Tooth disease
  • infantile-onset ascending hereditary spastic paralysis
  • juvenile primary lateral sclerosis
  • Noonan syndrome

Where can I find additional information about the ARHGEF gene family?

You may find the following resources about the ARHGEF gene family helpful.

  • Madame Curie Bioscience: Rho Proteins and Actin Polymerisation (
  • Madame Curie Bioscience: Rho Family GTPases and Cellular Transformation (

What glossary definitions help with understanding the ARHGEF gene family?

actin ; cell ; cytoskeleton ; differentiation ; disability ; domain ; gene ; GTP ; guanine ; leukemia ; molecule ; nucleotide ; pH ; progression ; proliferation ; sclerosis ; syndrome ; transcription ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


These sources were used to develop the Genetics Home Reference summary for the ARHGEF gene family.

  • Schmidt A, Hall A. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. Genes Dev. 2002 Jul 1;16(13):1587-609. Review. (
  • Aittaleb M, Boguth CA, Tesmer JJ. Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors. Mol Pharmacol. 2010 Feb;77(2):111-25. doi: 10.1124/mol.109.061234. Epub 2009 Oct 30. Review. (
  • Mulinari S, Häcker U. Rho-guanine nucleotide exchange factors during development: Force is nothing without control. Small GTPases. 2010 Jul;1(1):28-43. (
  • Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol. 2005 Feb;6(2):167-80. Review. (


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 healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: August 2012
Published: February 8, 2016