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Genetics Home Reference: your guide to understanding genetic conditions
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SKI

Reviewed February 2013

What is the official name of the SKI gene?

The official name of this gene is “SKI proto-oncogene.”

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

What is the normal function of the SKI gene?

The SKI gene provides instructions for making a protein involved in a signaling pathway that transmits chemical signals from the cell surface to the nucleus. This pathway, called the transforming growth factor beta (TGF-β) pathway, allows the environment outside the cell to affect how the cell produces other proteins. It helps regulate cell growth and division (proliferation), the process by which cells mature to carry out special functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). Through this pathway, a group of proteins called the SMAD complex is turned on (activated). The activated SMAD protein complex moves to the cell nucleus and attaches (binds) to specific areas of DNA to control the activity of particular genes, which help regulate various cellular processes.

The SKI protein controls the activity of the TGF-β pathway by binding to certain SMAD proteins, which interrupts signaling through the pathway. SKI protein binding within the cell can keep the SMAD protein complex from entering the nucleus, so it is unable to activate genes. Binding of the SKI protein can also occur in the nucleus. Although the SMAD complex binds to DNA, the SKI protein attracts other proteins (corepressors) that block its ability to turn genes on.

The SKI protein is found in many cell types throughout the body and appears to play a role in the development of many tissues, including the skull, other bones, skin, and brain.

Does the SKI gene share characteristics with other genes?

The SKI gene belongs to a family of genes called SKOR (SKI transcriptional corepressors).

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 SKI gene related to health conditions?

Shprintzen-Goldberg syndrome - caused by mutations in the SKI gene

At least 10 mutations in the SKI gene have been found in people with Shprintzen-Goldberg syndrome, a condition characterized by distinctive facial features, skeletal abnormalities, and intellectual disability. Most of these mutations change single protein building blocks (amino acids) in the SKI protein. Many of the mutations alter the region of the SKI protein that binds to SMAD proteins. It is thought that altered SKI proteins are unable to attach to SMAD proteins, which allows TGF-β signaling to continue uncontrolled. Excess TGF-β signaling changes the regulation of gene activity and likely disrupts development of many body systems, including the bones and brain, resulting in the wide range of signs and symptoms of Shprintzen-Goldberg syndrome.

Where is the SKI gene located?

Cytogenetic Location: 1p36.33

Molecular Location on chromosome 1: base pairs 2,228,694 to 2,310,212

The SKI gene is located on the short (p) arm of chromosome 1 at position 36.33.

The SKI gene is located on the short (p) arm of chromosome 1 at position 36.33.

More precisely, the SKI gene is located from base pair 2,228,694 to base pair 2,310,212 on chromosome 1.

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 SKI?

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

You may also be interested in these resources, which are designed for genetics professionals and researchers.

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

  • proto-oncogene c-Ski
  • SKI_HUMAN
  • ski oncogene
  • ski oncoprotein
  • v-ski avian sarcoma viral oncogene homolog
  • v-ski sarcoma viral oncogene homolog (avian)

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 SKI?

acids ; apoptosis ; cell ; cell nucleus ; differentiation ; disability ; DNA ; gene ; growth factor ; nucleus ; oncogene ; proliferation ; protein ; proto-oncogene ; sarcoma ; syndrome

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

References

  • Carmignac V, Thevenon J, Adès L, Callewaert B, Julia S, Thauvin-Robinet C, Gueneau L, Courcet JB, Lopez E, Holman K, Renard M, Plauchu H, Plessis G, De Backer J, Child A, Arno G, Duplomb L, Callier P, Aral B, Vabres P, Gigot N, Arbustini E, Grasso M, Robinson PN, Goizet C, Baumann C, Di Rocco M, Sanchez Del Pozo J, Huet F, Jondeau G, Collod-Beroud G, Beroud C, Amiel J, Cormier-Daire V, Rivière JB, Boileau C, De Paepe A, Faivre L. In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome. Am J Hum Genet. 2012 Nov 2;91(5):950-7. doi: 10.1016/j.ajhg.2012.10.002. Epub 2012 Oct 25. (http://www.ncbi.nlm.nih.gov/pubmed/23103230?dopt=Abstract)
  • Deheuninck J, Luo K. Ski and SnoN, potent negative regulators of TGF-beta signaling. Cell Res. 2009 Jan;19(1):47-57. doi: 10.1038/cr.2008.324. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19114989?dopt=Abstract)
  • Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destrée A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, Loeys BL, Dietz HC. Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet. 2012 Nov;44(11):1249-54. doi: 10.1038/ng.2421. Epub 2012 Sep 30. (http://www.ncbi.nlm.nih.gov/pubmed/23023332?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6497)
  • Suzuki H, Yagi K, Kondo M, Kato M, Miyazono K, Miyazawa K. c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. Oncogene. 2004 Jun 24;23(29):5068-76. (http://www.ncbi.nlm.nih.gov/pubmed/15107821?dopt=Abstract)
  • OMIM: V-SKI AVIAN SARCOMA VIRAL ONCOGENE HOMOLOG (http://omim.org/entry/164780)

 

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: February 2013
Published: December 16, 2014