ALX3 (gene)

The ALX3 gene, also known as aristaless-like homeobox 3, is a protein coding gene that provides instructions to build a protein which is a member of the homeobox protein family. This grouping regulates patterns of anatomical development. The gene encodes a nuclear protein that functions as a transcription regulator involved in cell-type differentiation and development.

The ALX3 protein, encoded by the gene, is a transcription factor, meaning that it binds to DNA and obtains control over the action of other genes. The ALX3 protein specifically controls genes that regulate cell growth, proliferation, and migration. This protein is essential for the development of the head and face, specifically the nose. This event begins around the fourth week of development.

At least 7 mutations in the ALX3 gene are known to cause frontonasal dysplasia. The mutations eliminate the function of the ALX3 protein, resulting in decreased ability to bind to DNA. The loss of regulatory function results in uncontrolled cell proliferation and migration during fetal development. One particular form of the disorder, called frontonasal dysplasia type 1, presents with abnormal development of structures in the middle of the face. The most common malformation of this defect is a cleft in the nose, lip, and palate.

References

• McGonnell IM, Graham A, Richardson J, Fish JL, Depew MJ, Dee CT, Holland PW, Takahashi T. Evolution of the Alx homeobox gene family: parallel retention and independent loss of the vertebrate Alx3 gene. Evol Dev. 2011 Jul-Aug;13(4):343-51. doi: 10.1111/j.1525-142X.2011.00489.x
• Twigg, S. R. F., Versnel, S. L., Nurnberg, G., Lees, M. M., Bhat, M., Hammond, P., Hennekam, R. C. M., Hoogeboom, A. J. M., Hurst, J. A., Johnson, D., Robinson, A. A., Scambler, P. J., Gerrelli, D., Nurnberg, P., Mathijssen, I. M. J., Wilkie, A. O. M. Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene. Am. J. Hum. Genet. 84: 698-705, 2009.