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Normal Function
The CCBE1 gene provides instructions for making a protein that is found in the extracellular matrix, which is the lattice of proteins and other molecules that forms in the spaces between cells. Early in development, the CCBE1 protein is involved in the formation of the lymphatic system, which is a network of vessels that transport white blood cells (lymphocytes), nutrients, and proteins in a fluid called lymph.
The CCBE1 protein helps guide the maturation (differentiation) and movement (migration) of immature cells called lymphangioblasts that will eventually form the lining (epithelium) of lymphatic vessels. Additionally, the CCBE1 protein works with a protein produced from the ADAMTS3 gene to help regulate the activity of a protein called vascular endothelial growth factor receptor 3 (VEGFR3). VEGFR3 plays a key role in the development and maintenance of the lymphatic system.
Health Conditions Related to Genetic Changes
Hennekam syndrome
Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the CCBE1 gene cause Hennekam syndrome, an inherited disorder that is characterized by abnormalities of the lymphatic system. People with Hennekam syndrome often have dilated lymphatic vessels (lymphangiectasias) and an accumulation of lymph (lymphedema) in various tissues.
Many of the pathogenic CCBE1 gene variants that are associated with Hennekam syndrome cause cells to make a version of the protein that does not function properly. As a result, VEGFR3 protein activity is disrupted and the formation of the lymphatic vessels is impaired, which leads to the lymphangiectasia and lymphedema seen in people with this condition.
More About This Health ConditionOther Names for This Gene
- FLJ30681
- KIAA1983
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Alders M, Hogan BM, Gjini E, Salehi F, Al-Gazali L, Hennekam EA, Holmberg EE, Mannens MM, Mulder MF, Offerhaus GJ, Prescott TE, Schroor EJ, Verheij JB, Witte M, Zwijnenburg PJ, Vikkula M, Schulte-Merker S, Hennekam RC. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet. 2009 Dec;41(12):1272-4. doi: 10.1038/ng.484. Citation on PubMed
- Bos FL, Caunt M, Peterson-Maduro J, Planas-Paz L, Kowalski J, Karpanen T, van Impel A, Tong R, Ernst JA, Korving J, van Es JH, Lammert E, Duckers HJ, Schulte-Merker S. CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ Res. 2011 Aug 19;109(5):486-91. doi: 10.1161/CIRCRESAHA.111.250738. Epub 2011 Jul 21. Citation on PubMed
- Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M. Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. Hum Mol Genet. 2017 Nov 1;26(21):4095-4104. doi: 10.1093/hmg/ddx297. Citation on PubMed
- Connell F, Kalidas K, Ostergaard P, Brice G, Homfray T, Roberts L, Bunyan DJ, Mitton S, Mansour S, Mortimer P, Jeffery S; Lymphoedema Consortium. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet. 2010 Feb;127(2):231-41. doi: 10.1007/s00439-009-0766-y. Epub 2009 Nov 13. Citation on PubMed
- Scheuerle AE, Sweed NT, Timmons CF, Smith ED, Alcaraz WA, Shinde DN. An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3. Am J Med Genet A. 2018 Dec;176(12):2858-2861. doi: 10.1002/ajmg.a.40633. Epub 2018 Nov 18. Citation on PubMed
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