Short-stature homeobox gene

The short-stature homeobox gene (SHOX), also known as short-stature-homeobox-containing gene, is a gene located on both the X and Y chromosomes, which is associated with short stature in humans if mutated or present in only one copy (haploinsufficiency).

SHOX
Identifiers
Aliases	SHOX, GCFX, PHOG, SHOXY, SS, short stature homeobox
External IDs	OMIM: 312865, 400020 HomoloGene: 55463 GeneCards: SHOX
Gene ontology Molecular function • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • DNA binding • GO:0001948 protein binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • sequence-specific DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cell nucleus • nucleoplasm • intracellular membrane-bounded organelle Biological process • multicellular organism development • skeletal system development • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6473	n/a
Ensembl	ENSG00000185960	n/a
UniProt	O15266	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	NP_000442 NP_006874	n/a
Location (UCSC)	n/a	n/a
PubMed search	[1]	n/a
Wikidata
View/Edit Human

Pathology

SHOX was first found during a search for the cause of short stature in women with Turner syndrome, where there is loss of genetic material from the X chromosome, typically by loss of one entire X chromosome.[2]

Since its discovery, the gene has been found to play a role in idiopathic short stature, Léri-Weill dyschondrosteosis, and Langer mesomelic dysplasia.

Gene dosage effects of extra copies of SHOX may be a cause of the increased stature seen in other sex chromosome aneuploidy conditions such as triple X, XYY, Klinefelter, XXYY and similar syndromes.[3]

Genetics and function

SHOX is composed of 6 different exons and is located in the pseudoautosomal region (PAR1) of the X chromosome (Xp22.33) and Y chromosome.[2] Similar genes are present in a variety of animals and insects.

It is a homeobox gene, meaning that it helps to regulate development.

References

1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
2. "SHOX - short stature homeobox - Genetics Home Reference". U.S. National Library of Medicine. 2005-09-01. Retrieved 2008-02-18.
3. Kanaka-Gantenbein C, Kitsiou S, Mavrou A, Stamoyannou L, Kolialexi A, Kekou K, Liakopoulou M, Chrousos G (2004). "Tall stature, insulin resistance, and disturbed behavior in a girl with the triple X syndrome harboring three SHOX genes: offspring of a father with mosaic Klinefelter syndrome but with two maternal X chromosomes". Horm. Res. 61 (5): 205–10. doi:10.1159/000076532. PMID 14752208.

Further reading

• Bernasconi S, Mariani S, Falcinelli C, et al. (2002). "SHOX gene in Leri-Weill syndrome and in idiopathic short stature". J. Endocrinol. Invest. 24 (9): 737–41. doi:10.1007/bf03343919. hdl:11380/613021. PMID 11716161.
• Leka SK, Kitsiou-Tzeli S, Kalpini-Mavrou A, Kanavakis E (2006). "Short stature and dysmorphology associated with defects in the SHOX gene". Hormones (Athens, Greece). 5 (2): 107–18. doi:10.14310/horm.2002.11174. PMID 16807223.
• Ballabio A, Bardoni B, Carrozzo R, et al. (1990). "Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome". Proc. Natl. Acad. Sci. U.S.A. 86 (24): 10001–5. doi:10.1073/pnas.86.24.10001. PMC 298630. PMID 2602357.
• Zuffardi O, Maraschio P, Lo Curto F, et al. (1982). "The role of Yp in sex determination: new evidence from X/Y translocations". Am. J. Med. Genet. 12 (2): 175–84. doi:10.1002/ajmg.1320120207. PMID 6954848.
• Kuznetzova T, Baranov A, Ivaschenko T, et al. (1995). "X;Y translocation in a girl with short stature and some features of Turner's syndrome: cytogenetic and molecular studies". J. Med. Genet. 31 (8): 649–51. doi:10.1136/jmg.31.8.649. PMC 1050031. PMID 7815426.
• Ogata T, Yoshizawa A, Muroya K, et al. (1996). "Short stature in a girl with partial monosomy of the pseudoautosomal region distal to DXYS15: further evidence for the assignment of the critical region for a pseudoautosomal growth gene(s)". J. Med. Genet. 32 (10): 831–4. doi:10.1136/jmg.32.10.831. PMC 1051714. PMID 8558568.
• Rao E, Weiss B, Fukami M, et al. (1997). "Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome". Nat. Genet. 16 (1): 54–63. doi:10.1038/ng0597-54. PMID 9140395.
• Rao E, Weiss B, Fukami M, et al. (1997). "FISH-deletion mapping defines a 270-kb short stature critical interval in the pseudoautosomal region PAR1 on human sex chromosomes". Hum. Genet. 100 (2): 236–9. doi:10.1007/s004390050497. PMID 9254856.
• Ellison JW, Wardak Z, Young MF, et al. (1997). "PHOG, a candidate gene for involvement in the short stature of Turner syndrome". Hum. Mol. Genet. 6 (8): 1341–7. doi:10.1093/hmg/6.8.1341. PMID 9259282.
• Belin V, Cusin V, Viot G, et al. (1998). "SHOX mutations in dyschondrosteosis (Leri-Weill syndrome)". Nat. Genet. 19 (1): 67–9. doi:10.1038/ng0198-67. PMID 9590292.
• Shears DJ, Vassal HJ, Goodman FR, et al. (1998). "Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis". Nat. Genet. 19 (1): 70–3. doi:10.1038/ng0198-70. PMID 9590293.
• Grigelioniene G, Eklöf O, Ivarsson SA, et al. (2000). "Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia". Hum. Genet. 107 (2): 145–9. doi:10.1007/s004390000352. PMID 11030412.
• Huber C, Cusin V, Le Merrer M, et al. (2001). "SHOX point mutations in dyschondrosteosis". J. Med. Genet. 38 (5): 323. doi:10.1136/jmg.38.5.323. PMC 1734877. PMID 11403039.
• Rao E, Blaschke RJ, Marchini A, et al. (2002). "The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator". Hum. Mol. Genet. 10 (26): 3083–91. doi:10.1093/hmg/10.26.3083. PMID 11751690.
• Ezquieta B, Cueva E, Oliver A, Gracia R (2002). "SHOX intragenic microsatellite analysis in patients with short stature". J. Pediatr. Endocrinol. Metab. 15 (2): 139–48. doi:10.1515/jpem.2002.15.2.139. PMID 11874178.
• Ogata T, Muroya K, Sasaki G, et al. (2002). "SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features". J. Clin. Endocrinol. Metab. 87 (3): 1390–4. doi:10.1210/jc.87.3.1390. PMID 11889214.
• Rappold GA, Fukami M, Niesler B, et al. (2002). "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. 87 (3): 1402–6. doi:10.1210/jc.87.3.1402. PMID 11889216.
• Cormier-Daire V, Huber C, Munnich A (2002). "Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome)". Am. J. Med. Genet. 106 (4): 272–4. doi:10.1002/ajmg.10228. PMID 11891678.
• May CA, Shone AC, Kalaydjieva L, et al. (2002). "Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX". Nat. Genet. 31 (3): 272–5. doi:10.1038/ng918. PMID 12089524.

External links

• short+stature+homeobox+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReview/NCBI/NIH/UW entry on SHOX-Related Haploinsufficiency Disorders