The VLDLR gene provides instructions for making a protein called a very low density lipoprotein (VLDL) receptor. This protein is active in many different organs and tissues, including the heart, muscles used for movement (skeletal muscles), fatty (adipose) tissue, and the kidneys. The VLDL receptor appears to play a particularly important role in the developing brain.
The VLDL receptor works together with a protein called reelin. Reelin fits into the VLDL receptor like a key in a lock, which triggers a series of chemical reactions within the cell. During early brain development, the reelin signaling pathway helps to guide the movement of immature nerve cells (neuroblasts) to their appropriate locations in the brain.
Health Conditions Related to Genetic Changes
VLDLR-associated cerebellar hypoplasia
At least six mutations in the VLDLR gene have been found to cause VLDLR-associated cerebellar hypoplasia. These mutations prevent cells from producing any functional VLDL receptor protein. Without this protein, neuroblasts cannot reach the parts of the brain where they are needed. These problems with brain development predominantly affect the cerebellum, which is the part of the brain that coordinates movement. People with VLDLR-associated cerebellar hypoplasia have an unusually small and underdeveloped cerebellum, which leads to problems with balance and coordination (ataxia) and impaired speech. Other regions of the brain are also affected, resulting in intellectual disability and the other major features of this condition.More About This Health Condition
Other Names for This Gene
- VLDL receptor
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Boycott KM, Bonnemann C, Herz J, Neuert S, Beaulieu C, Scott JN, Venkatasubramanian A, Parboosingh JS. Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome). J Child Neurol. 2009 Oct;24(10):1310-5. doi: 10.1177/0883073809332696. Epub 2009 Mar 30. Citation on PubMed or Free article on PubMed Central
- Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS. Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet. 2005 Sep;77(3):477-83. doi: 10.1086/444400. Epub 2005 Jul 22. Citation on PubMed or Free article on PubMed Central
- Moheb LA, Tzschach A, Garshasbi M, Kahrizi K, Darvish H, Heshmati Y, Kordi A, Najmabadi H, Ropers HH, Kuss AW. Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome. Eur J Hum Genet. 2008 Feb;16(2):270-3. doi: 10.1038/sj.ejhg.5201967. Epub 2007 Nov 28. Citation on PubMed
- Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U. Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4232-6. doi: 10.1073/pnas.0710010105. Epub 2008 Mar 7. Citation on PubMed or Free article on PubMed Central
- Takahashi S, Sakai J, Fujino T, Hattori H, Zenimaru Y, Suzuki J, Miyamori I, Yamamoto TT. The very low-density lipoprotein (VLDL) receptor: characterization and functions as a peripheral lipoprotein receptor. J Atheroscler Thromb. 2004;11(4):200-8. doi: 10.5551/jat.11.200. Citation on PubMed
- Tissir F, Goffinet AM. Reelin and brain development. Nat Rev Neurosci. 2003 Jun;4(6):496-505. doi: 10.1038/nrn1113. No abstract available. Citation on PubMed
- Turkmen S, Hoffmann K, Demirhan O, Aruoba D, Humphrey N, Mundlos S. Cerebellar hypoplasia, with quadrupedal locomotion, caused by mutations in the very low-density lipoprotein receptor gene. Eur J Hum Genet. 2008 Sep;16(9):1070-4. doi: 10.1038/ejhg.2008.73. Epub 2008 Mar 26. Citation on PubMed
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