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DLL3

Reviewed February 2011

What is the official name of the DLL3 gene?

The official name of this gene is “delta-like 3 (Drosophila).”

DLL3 is the gene's official symbol. The DLL3 gene is also known by other names, listed below.

What is the normal function of the DLL3 gene?

The DLL3 gene provides instructions for making a protein that helps control (regulate) the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of vertebrae. Specifically, the DLL3 protein and the Notch pathway are involved in separating future vertebrae from one another during early development, a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein, to be turned on and off in a specific pattern (oscillate).

The DLL3 protein regulates the activity of the NOTCH1 protein. The DLL3 protein attaches (binds) to the inactive NOTCH1 protein and isolates (sequesters) it or marks it to be broken down so that it cannot be activated.

How are changes in the DLL3 gene related to health conditions?

spondylocostal dysostosis - caused by mutations in the DLL3 gene

More than 25 mutations in the DLL3 gene have been found to cause spondylocostal dysostosis type 1, the most common type of spondylocostal dysostosis. This condition is characterized by the abnormal development of bones in the spine and ribs. The known mutations in the DLL3 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the DLL3 protein is nonfunctional or absent, the NOTCH1 protein is abnormally active and does not oscillate, so somite segmentation does not occur properly. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis type 1.

Where is the DLL3 gene located?

Cytogenetic Location: 19q13

Molecular Location on chromosome 19: base pairs 39,498,916 to 39,508,480

The DLL3 gene is located on the long (q) arm of chromosome 19 at position 13.

The DLL3 gene is located on the long (q) arm of chromosome 19 at position 13.

More precisely, the DLL3 gene is located from base pair 39,498,916 to base pair 39,508,480 on chromosome 19.

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 DLL3?

You and your healthcare professional may find the following resources about DLL3 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 DLL3 gene or gene products?

  • delta3
  • delta-like protein 3
  • delta-like protein 3 isoform 1 precursor
  • delta-like protein 3 isoform 2 precursor
  • DLL3_HUMAN
  • drosophila Delta homolog 3
  • SCDO1

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 DLL3?

embryonic ; gene ; malformation ; precursor ; protein

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

References

  • Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat Genet. 2000 Apr;24(4):438-41. (http://www.ncbi.nlm.nih.gov/pubmed/10742114?dopt=Abstract)
  • Chapman G, Sparrow DB, Kremmer E, Dunwoodie SL. Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis. Hum Mol Genet. 2011 Mar 1;20(5):905-16. doi: 10.1093/hmg/ddq529. Epub 2010 Dec 7. (http://www.ncbi.nlm.nih.gov/pubmed/21147753?dopt=Abstract)
  • Ferjentsik Z, Hayashi S, Dale JK, Bessho Y, Herreman A, De Strooper B, del Monte G, de la Pompa JL, Maroto M. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009 Sep;5(9):e1000662. doi: 10.1371/journal.pgen.1000662. Epub 2009 Sep 25. (http://www.ncbi.nlm.nih.gov/pubmed/19779553?dopt=Abstract)
  • Gene Review: Spondylocostal Dysostosis, Autosomal Recessive (http://www.ncbi.nlm.nih.gov/books/NBK8828/)
  • Gibb S, Maroto M, Dale JK. The segmentation clock mechanism moves up a notch. Trends Cell Biol. 2010 Oct;20(10):593-600. doi: 10.1016/j.tcb.2010.07.001. Epub 2010 Aug 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20724159?dopt=Abstract)
  • Ladi E, Nichols JT, Ge W, Miyamoto A, Yao C, Yang LT, Boulter J, Sun YE, Kintner C, Weinmaster G. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. J Cell Biol. 2005 Sep 12;170(6):983-92. Epub 2005 Sep 6. (http://www.ncbi.nlm.nih.gov/pubmed/16144902?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/10683)
  • Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, Saga Y. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite. Development. 2010 May;137(9):1515-22. doi: 10.1242/dev.044545. Epub 2010 Mar 24. (http://www.ncbi.nlm.nih.gov/pubmed/20335362?dopt=Abstract)
  • OMIM: DELTA-LIKE 3 (http://omim.org/entry/602768)
  • Sparrow DB, Chapman G, Turnpenny PD, Dunwoodie SL. Disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res C Embryo Today. 2007 Jun;81(2):93-110. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17600782?dopt=Abstract)
  • Turnpenny PD, Whittock N, Duncan J, Dunwoodie S, Kusumi K, Ellard S. Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis. J Med Genet. 2003 May;40(5):333-9. (http://www.ncbi.nlm.nih.gov/pubmed/12746394?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: February 2011
Published: August 18, 2014