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Genetics Home Reference: your guide to understanding genetic conditions
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Homeobox gene family

Reviewed October 2012

What are the homeobox genes?

Homeobox genes are a large family of similar genes that direct the formation of many body structures during early embryonic development. In humans, the homeobox gene family contains an estimated 235 functional genes and 65 pseudogenes (structurally similar genes that do not provide instructions for making proteins). Homeobox genes are present on every human chromosome, and they often appear in clusters. Many classes and subfamilies of homeobox genes have been described, although these groupings are used inconsistently.

Homeobox genes contain a particular DNA sequence that provides instructions for making a string of 60 protein building blocks (amino acids) known as the homeodomain. Most homeodomain-containing proteins act as transcription factors, which means they bind to and control the activity of other genes. The homeodomain is the part of the protein that attaches (binds) to specific regulatory regions of the target genes.

Genes in the homeobox family are involved in a wide range of critical activities during development. These activities include directing the formation of limbs and organs along the anterior-posterior axis (the imaginary line that runs from head to tail in animals) and regulating the process by which cells mature to carry out specific functions (differentiation). Some homeobox genes act as tumor suppressors, which means they help prevent cells from growing and dividing too rapidly or in an uncontrolled way.

Because homeobox genes have so many important functions, mutations in these genes are responsible for a variety of developmental disorders. For example, mutations in the HOX group of homeobox genes typically cause limb malformations. Changes in PAX homeobox genes often result in eye disorders, and changes in MSX homeobox genes cause abnormal head, face, and tooth development. Additionally, increased or decreased activity of certain homeobox genes has been associated with several forms of cancer later in life.

Which genes are included in the homeobox gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides a list of genes in the homeobox family (http://www.genenames.org/genefamilies/homeobox).

Genetics Home Reference summarizes the normal function and health implications of these members of the homeobox gene family: ALX1, ALX3, ALX4, ARX, DUX4, HESX1, HOXA13, LMX1B, MSX1, MSX2, OTX2, PAX2, PAX3, PAX6, PAX8, PHOX2A, PHOX2B, PITX2, POU3F4, PROP1, SHOX, SIX1, SIX3, SIX5, TGIF1, and ZEB2.

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

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

  • aniridia
  • Axenfeld-Rieger syndrome
  • branchiootorenal syndrome
  • coloboma
  • combined pituitary hormone deficiency
  • congenital central hypoventilation syndrome
  • congenital fibrosis of the extraocular muscles
  • congenital hypothyroidism
  • craniofacial-deafness-hand syndrome
  • enlarged parietal foramina
  • facioscapulohumeral muscular dystrophy
  • frontonasal dysplasia
  • Gillespie syndrome
  • hand-foot-genital syndrome
  • Langer mesomelic dysplasia
  • Léri-Weill dyschondrosteosis
  • microphthalmia
  • Mowat-Wilson syndrome
  • nail-patella syndrome
  • neuroblastoma
  • nonsyndromic deafness
  • nonsyndromic holoprosencephaly
  • Partington syndrome
  • Peters anomaly
  • Potocki-Shaffer syndrome
  • renal coloboma syndrome
  • septo-optic dysplasia
  • Turner syndrome
  • Waardenburg syndrome
  • Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome
  • Wolf-Hirschhorn syndrome
  • X-linked infantile spasm syndrome
  • X-linked lissencephaly with abnormal genitalia

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

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

  • The Embryo Project Encyclopedia--Homeobox Genes and the Homeobox (http://embryo.asu.edu/pages/homeobox-genes-and-homeobox) (Arizona State University)
  • National Human Genome Research Institute: Homeodomain Resource (http://research.nhgri.nih.gov/homeodomain/) (National Institutes of Health)

What glossary definitions help with understanding the homeobox gene family?

acids ; anterior ; axis ; cancer ; chromosome ; class ; differentiation ; DNA ; embryonic ; gene ; homeobox ; homeodomain ; posterior ; Pro ; protein ; regulatory regions ; short stature ; stature ; transcription ; transcription factor ; tumor

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

References

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

  • Holland PW, Booth HA, Bruford EA. Classification and nomenclature of all human homeobox genes. BMC Biol. 2007 Oct 26;5:47. (http://www.ncbi.nlm.nih.gov/pubmed/17963489?dopt=Abstract)
  • Zhao Y, Westphal H. Homeobox genes and human genetic disorders. Curr Mol Med. 2002 Feb;2(1):13-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11898846?dopt=Abstract)
  • Boncinelli E. Homeobox genes and disease. Curr Opin Genet Dev. 1997 Jun;7(3):331-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/9229108?dopt=Abstract)
  • Cillo C, Cantile M, Faiella A, Boncinelli E. Homeobox genes in normal and malignant cells. J Cell Physiol. 2001 Aug;188(2):161-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11424082?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: December 16, 2014