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Genetics Home Reference: your guide to understanding genetic conditions
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SIL1

Reviewed September 2008

What is the official name of the SIL1 gene?

The official name of this gene is “SIL1 nucleotide exchange factor.”

SIL1 is the gene's official symbol. The SIL1 gene is also known by other names, listed below.

What is the normal function of the SIL1 gene?

The SIL1 gene provides instructions for producing a protein located in a cell structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. The SIL1 protein works with BiP, a protein that helps fold newly produced proteins into the proper shape and refold damaged proteins. To start this process, BiP attaches (binds) to a molecule called adenosine triphosphate (ATP). When BiP folds a protein, the ATP is converted to a similar molecule called adenosine diphosphate (ADP). Then the SIL1 protein releases ADP from BiP so that it can bind to another molecule of ATP and start the protein folding process again. Because of its role in helping BiP exchange ADP for ATP, the SIL1 protein is called a nucleotide exchange factor.

How are changes in the SIL1 gene related to health conditions?

Marinesco-Sjögren syndrome - caused by mutations in the SIL1 gene

More than a dozen mutations in the SIL1 gene have been found to cause Marinesco-Sjögren syndrome. Most of these mutations result in the production of a protein that has little or no activity. Defective SIL1 protein cannot remove ADP from BiP. BiP is then unable to bind to ATP and re-start the protein folding process. A disruption in protein folding impairs protein transport and causes proteins to accumulate in the endoplasmic reticulum. This accumulation likely damages and destroys cells in many different tissues, leading to poor coordination, muscle weakness, and the other features of Marinesco-Sjögren syndrome.

Where is the SIL1 gene located?

Cytogenetic Location: 5q31

Molecular Location on chromosome 5: base pairs 138,946,719 to 139,198,375

The SIL1 gene is located on the long (q) arm of chromosome 5 at position 31.

The SIL1 gene is located on the long (q) arm of chromosome 5 at position 31.

More precisely, the SIL1 gene is located from base pair 138,946,719 to base pair 139,198,375 on chromosome 5.

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 SIL1?

You and your healthcare professional may find the following resources about SIL1 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 SIL1 gene or gene products?

  • BAP
  • BiP-associated protein
  • MSS
  • SIL1 homolog, endoplasmic reticulum chaperone (S. cerevisiae)
  • SIL1_HUMAN
  • SIL1 protein
  • ULG5

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 SIL1?

adenosine diphosphate ; adenosine triphosphate ; ADP ; ATP ; cell ; chaperone ; endoplasmic reticulum ; gene ; molecule ; nucleotide ; protein ; 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

  • Anttonen AK, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, Koenig M, Eeg-Olofsson O, Udd B, Somer M, Somer H, Lehesjoki AE. The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. Nat Genet. 2005 Dec;37(12):1309-11. Epub 2005 Nov 13. (http://www.ncbi.nlm.nih.gov/pubmed/16282978?dopt=Abstract)
  • Anttonen AK, Siintola E, Tranebjaerg L, Iwata NK, Bijlsma EK, Meguro H, Ichikawa Y, Goto J, Kopra O, Lehesjoki AE. Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjögren syndrome. Eur J Hum Genet. 2008 Aug;16(8):961-9. doi: 10.1038/ejhg.2008.22. Epub 2008 Feb 20. (http://www.ncbi.nlm.nih.gov/pubmed/18285827?dopt=Abstract)
  • Eriguchi M, Mizuta H, Kurohara K, Fujitake J, Kuroda Y. Identification of a new homozygous frameshift insertion mutation in the SIL1 gene in 3 Japanese patients with Marinesco-Sjögren syndrome. J Neurol Sci. 2008 Jul 15;270(1-2):197-200. doi: 10.1016/j.jns.2008.02.012. Epub 2008 Apr 18. (http://www.ncbi.nlm.nih.gov/pubmed/18395226?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/64374)
  • Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, Rudnik-Schöneborn S, Blaschek A, Wolf NI, Harting I, North K, Smith J, Muntoni F, Brockington M, Quijano-Roy S, Renault F, Herrmann R, Hendershot LM, Schröder JM, Lochmüller H, Topaloglu H, Voit T, Weis J, Ebinger F, Zerres K. Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy. Nat Genet. 2005 Dec;37(12):1312-4. Epub 2005 Nov 13. (http://www.ncbi.nlm.nih.gov/pubmed/16282977?dopt=Abstract)
  • OMIM: SIL1, S. CEREVISIAE, HOMOLOG OF (http://omim.org/entry/608005)
  • Van Raamsdonk JM. Loss of function mutations in SIL1 cause Marinesco-Sjögren syndrome. Clin Genet. 2006 May;69(5):399-400. (http://www.ncbi.nlm.nih.gov/pubmed/16650075?dopt=Abstract)
  • Zimmermann R, Müller L, Wullich B. Protein transport into the endoplasmic reticulum: mechanisms and pathologies. Trends Mol Med. 2006 Dec;12(12):567-73. Epub 2006 Oct 30. (http://www.ncbi.nlm.nih.gov/pubmed/17071140?dopt=Abstract)
  • Zoghbi HY. SILencing misbehaving proteins. Nat Genet. 2005 Dec;37(12):1302-3. (http://www.ncbi.nlm.nih.gov/pubmed/16314860?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: September 2008
Published: September 15, 2014