PHOX2A

Reviewed March 2009

What is the official name of the PHOX2A gene?

The official name of this gene is “paired-like homeobox 2a.”

PHOX2A is the gene's official symbol. The PHOX2A gene is also known by other names, listed below.

What is the normal function of the PHOX2A gene?

The PHOX2A gene provides instructions for making a protein that is found in the nervous system. This protein acts early in development to help promote the formation of nerve cells (neurons) and regulate the process by which the neurons mature to carry out specific functions (differentiation).

Most of researchers' knowledge about the PHOX2A protein comes from studies in other animals. From these studies, it is clear that the protein plays a critical role in the development of the autonomic nervous system, which controls involuntary body functions such as breathing, blood pressure, heart rate, and digestion. The PHOX2A protein is also involved in the formation of certain nerves in the head and face. Specifically, it appears to be critical for the development and function of cranial nerves III and IV, which emerge from the brain and control many of the muscles that surround the eyes (extraocular muscles). These muscles direct eye movement and determine the position of the eyes.

Does the PHOX2A gene share characteristics with other genes?

The PHOX2A gene belongs to a family of genes called homeobox (homeoboxes).

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 PHOX2A gene related to health conditions?

congenital fibrosis of the extraocular muscles - caused by mutations in the PHOX2A gene

At least four mutations in the PHOX2A gene can cause congenital fibrosis of the extraocular muscles. These mutations are responsible for a form of the disorder called CFEOM2, which has been identified in several families of Middle Eastern descent.

Most of the mutations that cause congenital fibrosis of the extraocular muscles result in the production of an abnormally short, nonfunctional version of the PHOX2A protein. In humans, a lack of this protein prevents the normal development of several cranial nerves and the extraocular muscles they control. Abnormal development and function of these muscles leads to the characteristic features of the disorder, including restricted eye movement and related problems with vision. Although the PHOX2A protein plays an important role in autonomic nervous system development, PHOX2A mutations do not seem to affect the function of this part of the nervous system.

Where is the PHOX2A gene located?

Cytogenetic Location: 11q13.2

Molecular Location on chromosome 11: base pairs 71,950,120 to 71,955,219

The PHOX2A gene is located on the long (q) arm of chromosome 11 at position 13.2.

More precisely, the PHOX2A gene is located from base pair 71,950,120 to base pair 71,955,219 on chromosome 11.

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 PHOX2A?

You and your healthcare professional may find the following resources about PHOX2A helpful.

Educational resources - Information pages
- Neuroscience (2nd edition, 2001): The Actions and Innervation of Extraocular Muscles (http://www.ncbi.nlm.nih.gov/books/NBK10793/)
- The Engle Laboratory, Children's Hospital Boston: Learn about CFEOM2/PHOX2A (http://www.childrenshospital.org/cfapps/research/data_admin/Site339/mainpageS339P21.html)
Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1348/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PHOX2A (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=401%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=(PHOX2A%5BTIAB%5D)%20OR%20(ARIX%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/602753)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_PHOX2A.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/401)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=401)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=691)

What other names do people use for the PHOX2A gene or gene products?

aristaless homeobox homolog
aristaless homeobox protein homolog
ARIX
ARIX1 homeodomain protein
arix homeodomain protein
CFEOM2
FEOM2
MGC52227
NCAM2
paired mesoderm homeobox protein 2A
PHX2A_HUMAN
PMX2A

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 PHOX2A?

autonomic nervous system ; congenital ; cranial nerves ; differentiation ; digestion ; extraocular muscles ; fibrosis ; gene ; homeobox ; homeodomain ; involuntary ; mesoderm ; nervous system ; protein

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Benfante R, Flora A, Di Lascio S, Cargnin F, Longhi R, Colombo S, Clementi F, Fornasari D. Transcription factor PHOX2A regulates the human alpha3 nicotinic receptor subunit gene promoter. J Biol Chem. 2007 May 4;282(18):13290-302. Epub 2007 Mar 7. (http://www.ncbi.nlm.nih.gov/pubmed/17344216?dopt=Abstract)
Bosley TM, Oystreck DT, Robertson RL, al Awad A, Abu-Amero K, Engle EC. Neurological features of congenital fibrosis of the extraocular muscles type 2 with mutations in PHOX2A. Brain. 2006 Sep;129(Pt 9):2363-74. Epub 2006 Jun 30. (http://www.ncbi.nlm.nih.gov/pubmed/16815872?dopt=Abstract)
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/401)
Heidary G, Engle EC, Hunter DG. Congenital fibrosis of the extraocular muscles. Semin Ophthalmol. 2008 Jan-Feb;23(1):3-8. doi: 10.1080/08820530701745181. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18214786?dopt=Abstract)
Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH, Zwaan J, Mullaney PB, Bosley TM, Engle EC. Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nat Genet. 2001 Nov;29(3):315-20. (http://www.ncbi.nlm.nih.gov/pubmed/11600883?dopt=Abstract)
Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF. Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development. 1997 Oct;124(20):4065-75. (http://www.ncbi.nlm.nih.gov/pubmed/9374403?dopt=Abstract)
Yazdani A, Chung DC, Abbaszadegan MR, Al-Khayer K, Chan WM, Yazdani M, Ghodsi K, Engle EC, Traboulsi EI. A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). Am J Ophthalmol. 2003 Nov;136(5):861-5. (http://www.ncbi.nlm.nih.gov/pubmed/14597037?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.