The SHOX gene provides instructions for making a protein that regulates the activity of other genes. On the basis of this role, the SHOX protein is called a transcription factor. The SHOX gene is part of a large family of homeobox genes, which act during early embryonic development to control the formation of many body structures. Specifically, the SHOX gene is essential for the development of the skeleton. It plays a particularly important role in the growth and maturation of bones in the arms and legs.
One copy of the SHOX gene is located on each of the sex chromosomes (the X and Y chromosomes) in an area called the pseudoautosomal region. Although many genes are unique to either the X or Y chromosome, genes in the pseudoautosomal region are present on both chromosomes. As a result, both females (who have two X chromosomes) and males (who have one X and one Y chromosome) have two functional copies of the SHOX gene in each cell.
Health Conditions Related to Genetic Changes
Langer mesomelic dysplasia
Langer mesomelic dysplasia results from genetic changes involving both copies of the SHOX gene in each cell. Deletions of this gene are the most common change responsible for this condition. Mutations in the SHOX gene can also cause the condition, as can deletions of nearby genetic material that normally helps regulate the gene's activity. These changes greatly reduce or eliminate the amount of SHOX protein that is produced. A lack of this protein disrupts normal bone development and growth starting before birth. The resulting skeletal abnormalities include very short stature, extreme shortening of the long bones in the arms and legs (mesomelia), and an abnormality of the wrist and forearm bones known as Madelung deformity.More About This Health Condition
Léri-Weill dyschondrosteosis results from genetic changes involving one copy of the SHOX gene in each cell. Most commonly, this skeletal disorder is caused by a deletion of the SHOX gene. Other genetic changes that can cause the disorder include mutations in the SHOX gene or deletions of nearby genetic material that normally helps regulate the gene's activity. These changes reduce the amount of SHOX protein that is produced. A shortage of this protein disrupts normal bone development and growth starting before birth. The resulting skeletal abnormalities are similar to those of Langer mesomelic dysplasia (described above), although they tend to be less severe.More About This Health Condition
MedlinePlus Genetics provides information about Mayer-Rokitansky-Küster-Hauser syndromeMore About This Health Condition
Turner syndrome occurs when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally altered. Because the SHOX gene is located on the sex chromosomes, most women with Turner syndrome have only one copy of the gene in each cell instead of the usual two copies. Loss of one copy of this gene reduces the amount of SHOX protein that is produced. A shortage of this protein likely contributes to the short stature and skeletal abnormalities (such as unusual rotation of the wrist and elbow joints) often seen in females with this condition.More About This Health Condition
Deletions of the entire SHOX gene or mutations within or near the gene have been identified in some people with short stature. This short stature is usually described as idiopathic, which means it is not associated with the characteristic features of a disease or syndrome. However, some people with short stature and changes in the SHOX gene have been found to have subtle skeletal abnormalities.
Other Names for This Gene
- growth control factor, X-linked
- pseudoautosomal homeobox-containing osteogenic gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Binder G, Renz A, Martinez A, Keselman A, Hesse V, Riedl SW, Hausler G, Fricke-Otto S, Frisch H, Heinrich JJ, Ranke MB. SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. J Clin Endocrinol Metab. 2004 Sep;89(9):4403-8. doi: 10.1210/jc.2004-0591. Citation on PubMed
- Binder G. Short stature due to SHOX deficiency: genotype, phenotype, and therapy. Horm Res Paediatr. 2011 Feb;75(2):81-9. doi: 10.1159/000324105. Epub 2011 Feb 4. Citation on PubMed
- Campos-Barros A, Benito-Sanz S, Ross JL, Zinn AR, Heath KE. Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD). Am J Med Genet A. 2007 May 1;143A(9):933-8. doi: 10.1002/ajmg.a.31676. Citation on PubMed
- Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R, Robson SC, Binder G, Glass I, Strachan T, Lindsay S, Rappold GA. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet. 2000 Mar 22;9(5):695-702. doi: 10.1093/hmg/9.5.695. Citation on PubMed
- Falcinelli C, Iughetti L, Percesepe A, Calabrese G, Chiarelli F, Cisternino M, De Sanctis L, Pucarelli I, Radetti G, Wasniewska M, Weber G, Stuppia L, Bernasconi S, Forabosco A. SHOX point mutations and deletions in Leri-Weill dyschondrosteosis. J Med Genet. 2002 Jun;39(6):E33. doi: 10.1136/jmg.39.6.e33. No abstract available. Citation on PubMed or Free article on PubMed Central
- Hirschfeldova K, Solc R, Baxova A, Zapletalova J, Kebrdlova V, Gaillyova R, Prasilova S, Soukalova J, Mihalova R, Lnenicka P, Florianova M, Stekrova J. SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Leri-Weill dyschondrosteosis. Gene. 2012 Jan 10;491(2):123-7. doi: 10.1016/j.gene.2011.10.011. Epub 2011 Oct 14. Citation on PubMed
- Jorge AA, Funari MF, Nishi MY, Mendonca BB. Short stature caused by isolated SHOX gene haploinsufficiency: update on the diagnosis and treatment. Pediatr Endocrinol Rev. 2010 Dec;8(2):79-85. Citation on PubMed
- Marchini A, Rappold G, Schneider KU. SHOX at a glance: from gene to protein. Arch Physiol Biochem. 2007 Jun;113(3):116-23. doi: 10.1080/13813450701531201. Citation on PubMed
- Rappold G, Blum WF, Shavrikova EP, Crowe BJ, Roeth R, Quigley CA, Ross JL, Niesler B. Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. J Med Genet. 2007 May;44(5):306-13. doi: 10.1136/jmg.2006.046581. Epub 2006 Dec 20. Citation on PubMed or Free article on PubMed Central
- Rappold GA, Fukami M, Niesler B, Schiller S, Zumkeller W, Bettendorf M, Heinrich U, Vlachopapadoupoulou E, Reinehr T, Onigata K, Ogata T. Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature. J Clin Endocrinol Metab. 2002 Mar;87(3):1402-6. doi: 10.1210/jcem.87.3.8328. Citation on PubMed
- Zinn AR, Wei F, Zhang L, Elder FF, Scott CI Jr, Marttila P, Ross JL. Complete SHOX deficiency causes Langer mesomelic dysplasia. Am J Med Genet. 2002 Jun 15;110(2):158-63. doi: 10.1002/ajmg.10422. Citation on PubMed
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