Normal Function
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, but it 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. This series of reactions is known as a signaling pathway. During early brain development, the reelin signaling pathway helps guide immature nerve cells (neuroblasts) to their appropriate locations.
Health Conditions Related to Genetic Changes
Dysequilibrium syndrome
Certain variants (also called mutations) in the VLDLR gene can cause dysequilibrium syndrome (DES). When this condition is caused by VLDLR gene variants, it is known as DES type 1, sometimes also called VLDLR-related cerebellar hypoplasia. DES is a group of disorders that are characterized by abnormal brain development, which causes intellectual disabilities and problems with balance and coordination (ataxia). People with DES type 1 have ataxia that is present from birth and typically does not worsen over time. Type 1 is the most common form of DES.
Many of the VLDLR gene variants that are associated with DES type 1 prevent cells from producing functional VLDL receptor protein. Without this protein, neuroblasts cannot reach the parts of the brain where they are needed. These problems with brain development mainly affect the cerebellum, which is the part of the brain that coordinates movement. In people with DES type 1, parts of the cerebellum are unusually small and underdeveloped, which contributes to the ataxia and speech difficulties seen in people with this condition.
More About This Health ConditionOther Names for This Gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- 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
- Boycott KM, MacDonald SK, Parboosingh JS. VLDLR Cerebellar Hypoplasia. 2008 Aug 26 [updated 2020 Feb 27]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1874/ Citation on PubMed
- Micalizzi A, Moroni I, Ginevrino M, Biagini T, Mazza T, Romani M, Valente EM. Very mild features of dysequilibrium syndrome associated with a novel VLDLR missense mutation. Neurogenetics. 2016 Jul;17(3):191-5. doi: 10.1007/s10048-016-0488-y. Epub 2016 Jun 2. Citation on PubMed
- 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
- Newman JM, Vogel H. Neuropathological findings of very low-density lipoprotein receptor-related cerebellar hypoplasia in a full-term fetus. J Neuropathol Exp Neurol. 2025 Dec 1;84(12):1135-1142. doi: 10.1093/jnen/nlaf110. Citation on PubMed
- 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
- Wali GM, Wali G. Broadening the Clinical Spectrum of Very Low Density Lipoprotein Receptor Associated Dysequilibrium Syndrome. Mov Disord Clin Pract. 2021 Apr 3;8(4):619-623. doi: 10.1002/mdc3.13184. eCollection 2021 May. No abstract available. Citation on PubMed
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