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Genetics Home Reference: your guide to understanding genetic conditions
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ALX4

Reviewed October 2012

What is the official name of the ALX4 gene?

The official name of this gene is “ALX homeobox 4.”

ALX4 is the gene's official symbol. The ALX4 gene is also known by other names, listed below.

What is the normal function of the ALX4 gene?

The ALX4 gene provides instructions for producing a protein that is necessary for proper development throughout the body, especially in the skull and limb bones. The ALX4 protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of certain genes. The presence of the ALX4 protein seems to be particularly critical for the complete development of the skull.

Does the ALX4 gene share characteristics with other genes?

The ALX4 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 ALX4 gene related to health conditions?

enlarged parietal foramina - caused by mutations in the ALX4 gene

A few mutations in the ALX4 gene have been identified in people with enlarged parietal foramina type 2. This condition is characterized by enlarged openings (foramina) in the two bones that make up much of the top and sides of the skull (the parietal bones). The mutations involved in this condition include a change of one protein building block (amino acid) in the ALX4 protein and deletions of one or more DNA building blocks (nucleotides) from the gene. These genetic changes result in the production of an unstable ALX4 protein that cannot bind to DNA. A nonfunctional ALX4 protein impairs the regulation of cell growth and division (proliferation); cell maturation and specialization (differentiation); and the balance of cell survival and self-destruction in certain areas of the skull. These impairments of cell function lead to problems with bone formation (ossification) in the skull, which cause enlarged parietal foramina.

Potocki-Shaffer syndrome - caused by mutations in the ALX4 gene

A mutation resulting in the deletion of the ALX4 gene causes a condition called Potocki-Shaffer syndrome. People with this condition have enlarged parietal foramina (described above) and multiple benign bone tumors (exostoses). Other signs and symptoms seen in some people with Potocki-Shaffer syndrome include intellectual disability, developmental delay, distinctive facial features, vision problems, and defects in the heart, kidneys, and urinary tract.

Potocki-Shaffer syndrome (also called proximal 11p deletion syndrome) is caused by a deletion of genetic material from the short (p) arm of chromosome 11. In people with this condition, a loss of the ALX4 gene within this region is responsible for enlarged parietal foramina. This feature occurs because a shortage of the ALX4 transcription factor caused by deletion of the gene disrupts several cellular processes and impairs proper bone formation (ossification). The loss of another gene, EXT2, in the same region of chromosome 11 underlies the multiple exostoses. The loss of additional genes in the deleted region likely contributes to the other features of Potocki-Shaffer syndrome.

Where is the ALX4 gene located?

Cytogenetic Location: 11p11.2

Molecular Location on chromosome 11: base pairs 44,282,277 to 44,331,715

The ALX4 gene is located on the short (p) arm of chromosome 11 at position 11.2.

The ALX4 gene is located on the short (p) arm of chromosome 11 at position 11.2.

More precisely, the ALX4 gene is located from base pair 44,282,277 to base pair 44,331,715 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 ALX4?

You and your healthcare professional may find the following resources about ALX4 helpful.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=msx2)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for ALX4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=60529%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=((ALX4%5BTIAB%5D)%20OR%20(aristaless-like%20homeobox%204%5BALL%5D))%20OR%20((FPP%5BALL%5D)%20OR%20(PFM%5BALL%5D)%20OR%20(enlarged%20parietal%20foramina%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201080%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/605420)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ALX4.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/60529)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=60529)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=450)

What other names do people use for the ALX4 gene or gene products?

  • ALX4_HUMAN
  • FPP
  • homeodomain transcription factor ALX4
  • KIAA1788
  • PFM
  • PFM2

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 ALX4?

amino acid ; benign ; bone formation ; cell ; chromosome ; deletion ; developmental delay ; differentiation ; DNA ; exostoses ; gene ; homeobox ; homeodomain ; mutation ; ossification ; proliferation ; protein ; proximal ; syndrome ; transcription ; transcription factor

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

References

  • Antonopoulou I, Mavrogiannis LA, Wilkie AO, Morriss-Kay GM. Alx4 and Msx2 play phenotypically similar and additive roles in skull vault differentiation. J Anat. 2004 Jun;204(6):487-99. (http://www.ncbi.nlm.nih.gov/pubmed/15198690?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/60529)
  • Gene Review: Enlarged Parietal Foramina (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=msx2)
  • Hall CR, Wu Y, Shaffer LG, Hecht JT. Familial case of Potocki-Shaffer syndrome associated with microdeletion of EXT2 and ALX4. Clin Genet. 2001 Nov;60(5):356-9. (http://www.ncbi.nlm.nih.gov/pubmed/11903336?dopt=Abstract)
  • Mavrogiannis LA, Antonopoulou I, Baxová A, Kutílek S, Kim CA, Sugayama SM, Salamanca A, Wall SA, Morriss-Kay GM, Wilkie AO. Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects. Nat Genet. 2001 Jan;27(1):17-8. (http://www.ncbi.nlm.nih.gov/pubmed/11137991?dopt=Abstract)
  • OMIM: ARISTALESS-LIKE 4, MOUSE, HOMOLOG OF (http://omim.org/entry/605420)
  • Romeike BF, Wuyts W. Proximal chromosome 11p contiguous gene deletion syndrome phenotype: case report and review of the literature. Clin Neuropathol. 2007 Jan-Feb;26(1):1-11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17290930?dopt=Abstract)
  • Wakui K, Gregato G, Ballif BC, Glotzbach CD, Bailey KA, Kuo PL, Sue WC, Sheffield LJ, Irons M, Gomez EG, Hecht JT, Potocki L, Shaffer LG. Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki-Shaffer syndrome. Eur J Hum Genet. 2005 May;13(5):528-40. (http://www.ncbi.nlm.nih.gov/pubmed/15852040?dopt=Abstract)
  • Wu YQ, Badano JL, McCaskill C, Vogel H, Potocki L, Shaffer LG. Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome. Am J Hum Genet. 2000 Nov;67(5):1327-32. Epub 2000 Oct 3. (http://www.ncbi.nlm.nih.gov/pubmed/11017806?dopt=Abstract)
  • Wuyts W, Cleiren E, Homfray T, Rasore-Quartino A, Vanhoenacker F, Van Hul W. The ALX4 homeobox gene is mutated in patients with ossification defects of the skull (foramina parietalia permagna, OMIM 168500). J Med Genet. 2000 Dec;37(12):916-20. (http://www.ncbi.nlm.nih.gov/pubmed/11106354?dopt=Abstract)
  • Wuyts W, Waeber G, Meinecke P, Schüler H, Goecke TO, Van Hul W, Bartsch O. Proximal 11p deletion syndrome (P11pDS): additional evaluation of the clinical and molecular aspects. Eur J Hum Genet. 2004 May;12(5):400-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14872200?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.

 
Reviewed: October 2012
Published: May 13, 2013