Health Topics
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Normal Function
The DLL4 gene provides instructions for making a protein that is part of a signaling pathway known as the Notch pathway, which is important for normal development of many tissues throughout the body. The DLL4 protein attaches to a receptor protein called Notch1, fitting together like a key into its lock. When a connection is made between DLL4 and Notch1, a series of signaling reactions is launched (the Notch pathway), affecting cell functions. In particular, signaling stimulated by DLL4 plays a role in development of blood vessels before birth and growth of new blood vessels (angiogenesis) throughout life.
Health Conditions Related to Genetic Changes
Adams-Oliver syndrome
At least nine DLL4 gene mutations have been found in people with Adams-Oliver syndrome, a condition characterized by areas of missing skin (aplasia cutis congenita), usually on the scalp, and malformations of the hands and feet. Some of these mutations lead to production of an abnormally short protein that is likely broken down quickly, causing a shortage of DLL4. Other mutations change single protein building blocks (amino acids) in the DLL4 protein. These changes are thought to alter the structure of the protein, impairing its ability to function. Loss of DLL4 function may underlie blood vessel abnormalities in people with Adams-Oliver syndrome; however, some people with DLL4-related Adams-Oliver syndrome do not have these abnormalities. It is not clear how loss of DLL4 function leads to the scalp and limb abnormalities characteristic of the condition. Researchers suggest these features may be due to abnormal blood vessel development before birth.
More About This Health ConditionOther Names for This Gene
- AOS6
- delta 4
- delta ligand 4
- delta-like 4 (Drosophila)
- delta-like 4 homolog
- delta-like 4 protein
- delta-like protein 4 precursor
- delta4
- drosophila Delta homolog 4
- hdelta2
- notch ligand delta-2
- notch ligand DLL4
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalen M, Gerhardt H, Betsholtz C. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007 Feb 15;445(7129):776-80. doi: 10.1038/nature05571. Epub 2007 Jan 28. Citation on PubMed
- Kume T. Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol Histopathol. 2010 May;25(5):637-46. doi: 10.14670/HH-25.637. Citation on PubMed or Free article on PubMed Central
- Meester JA, Southgate L, Stittrich AB, Venselaar H, Beekmans SJ, den Hollander N, Bijlsma EK, Helderman-van den Enden A, Verheij JB, Glusman G, Roach JC, Lehman A, Patel MS, de Vries BB, Ruivenkamp C, Itin P, Prescott K, Clarke S, Trembath R, Zenker M, Sukalo M, Van Laer L, Loeys B, Wuyts W. Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome. Am J Hum Genet. 2015 Sep 3;97(3):475-82. doi: 10.1016/j.ajhg.2015.07.015. Epub 2015 Aug 20. Citation on PubMed or Free article on PubMed Central
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.