Normal Function
The HEPACAM gene provides instructions for making a protein called GlialCAM. This protein is found in liver cells and certain brain cells known as glial cells. In liver cells, GlialCAM plays a role in the attachment of cells to one another (adhesion) and cell movement. In glial cells, GlialCAM attaches (binds) to other GlialCAM proteins or to other proteins called MLC1 and ClC-2. GlialCAM ensures that these proteins are transported to junctions that connect neighboring glial cells. The function of GlialCAM at the cell junction is unclear.
Health Conditions Related to Genetic Changes
Megalencephalic leukoencephalopathy with subcortical cysts
At least 20 mutations in the HEPACAM gene have been found to cause megalencephalic leukoencephalopathy with subcortical cysts.
This condition affects brain development and function, resulting in problems with movement and recurrent seizures. HEPACAM gene mutations lead to a protein that is unable to correctly transport proteins to the cell junction. It is unknown how a lack of functional GlialCAM protein (or certain other proteins) at neuronal cell junctions impairs brain development and function, causing the signs and symptoms of megalencephalic leukoencephalopathy with subcortical cysts.
Mutations in the HEPACAM gene cause two types of megalencephalic leukoencephalopathy with subcortical cysts, type 2A and type 2B; together, these types account for 20 percent of all cases. A major difference between the two types is that the signs and symptoms of type 2B improve over time. The reasons for this improvement are unclear.
More About This Health ConditionOther Names for This Gene
- FLJ25530
- glial cell adhesion molecule
- GlialCAM
- HECAM_HUMAN
- hepatocyte and glial cell adhesion molecule
- hepatocyte cell adhesion molecule
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Arnedo T, Aiello C, Jeworutzki E, Dentici ML, Uziel G, Simonati A, Pusch M, Bertini E, Estevez R. Expanding the spectrum of megalencephalic leukoencephalopathy with subcortical cysts in two patients with GLIALCAM mutations. Neurogenetics. 2014 Mar;15(1):41-8. doi: 10.1007/s10048-013-0381-x. Epub 2013 Nov 8. Citation on PubMed
- Arnedo T, Lopez-Hernandez T, Jeworutzki E, Capdevila-Nortes X, Sirisi S, Pusch M, Estevez R. Functional analyses of mutations in HEPACAM causing megalencephalic leukoencephalopathy. Hum Mutat. 2014 Oct;35(10):1175-8. doi: 10.1002/humu.22622. Epub 2014 Aug 18. Citation on PubMed
- Barrallo-Gimeno A, Estevez R. GlialCAM, a glial cell adhesion molecule implicated in neurological disease. Adv Neurobiol. 2014;8:47-59. doi: 10.1007/978-1-4614-8090-7_3. Citation on PubMed
- Lopez-Hernandez T, Ridder MC, Montolio M, Capdevila-Nortes X, Polder E, Sirisi S, Duarri A, Schulte U, Fakler B, Nunes V, Scheper GC, Martinez A, Estevez R, van der Knaap MS. Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. Am J Hum Genet. 2011 Apr 8;88(4):422-32. doi: 10.1016/j.ajhg.2011.02.009. Epub 2011 Mar 17. Citation on PubMed or Free article on PubMed Central
- Lopez-Hernandez T, Sirisi S, Capdevila-Nortes X, Montolio M, Fernandez-Duenas V, Scheper GC, van der Knaap MS, Casquero P, Ciruela F, Ferrer I, Nunes V, Estevez R. Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. Hum Mol Genet. 2011 Aug 15;20(16):3266-77. doi: 10.1093/hmg/ddr238. Epub 2011 May 30. Citation on PubMed
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