Normal Function
The SCARB2 gene provides instructions for making a protein called lysosomal integral membrane protein-2 (LIMP-2). As its name suggests, this protein is primarily found in the membrane of cellular structures called lysosomes, which are specialized compartments that digest and recycle materials. Before moving to the lysosome, the LIMP-2 protein is processed in a cellular structure called the endoplasmic reticulum. There, LIMP-2 attaches to an enzyme called beta-glucocerebrosidase and transports it to the lysosome. In lysosomes, beta-glucocerebrosidase breaks down a fatty substance called glucocerebroside. The LIMP-2 protein remains in the lysosomal membrane after transporting beta-glucocerebrosidase and is important for the stability of these structures.
The LIMP-2 protein has additional functions outside the lysosome. In the heart, the protein is found in regions known as intercalated discs, which connect individual heart muscle cells together to form strong fibers. The LIMP-2 protein appears to play a role when the heart muscle is abnormally enlarged and has to work harder than normal, although its exact function is not clear.
The LIMP-2 protein is sometimes found in the outer membrane that surrounds the cell. Certain viruses can attach to LIMP-2, which allows them to enter and infect the cell. In particular, enterovirus 71 and certain strains of coxsackievirus (A7, A14, and A16), which cause a viral infection known as hand, foot, and mouth disease, use the LIMP-2 protein.
Health Conditions Related to Genetic Changes
Action myoclonus–renal failure syndrome
At least 20 mutations in the SCARB2 gene have been associated with action myoclonus–renal failure (AMRF) syndrome. This rare condition causes episodes of involuntary muscle jerking or twitching, particularly when trying to make intentional movements (action myoclonus). Another common feature of AMRF syndrome is kidney (renal) disease; despite being referenced in the condition name, kidney function is not affected in every person with the condition.
SCARB2 gene mutations associated with AMRF syndrome lead to production of an altered LIMP-2 protein that is stuck in the endoplasmic reticulum and cannot get to the lysosome. As a result, the movement of beta-glucocerebrosidase to lysosomes is impaired. It is thought that a shortage of beta-glucocerebrosidase in these structures contributes to the signs and symptoms of AMRF syndrome, although the mechanism is unclear. Researchers are working to understand why some people with SCARB2 gene mutations have kidney problems and others do not.
More About This Health ConditionOther Names for This Gene
- 85 kDa lysosomal membrane sialoglycoprotein
- 85 kDa lysosomal sialoglycoprotein scavenger receptor class B, member 2
- AMRF
- CD36 antigen (collagen type I receptor, thrombospondin receptor)-like 2 (lysosomal integral membrane protein II)
- CD36 antigen-like 2
- CD36L2
- EPM4
- HLGP85
- LGP85
- LIMP II
- LIMP-2
- LIMPII
- lysosome membrane protein 2 isoform 1 precursor
- lysosome membrane protein 2 isoform 2 precursor
- lysosome membrane protein II
- scavenger receptor class B, member 2
- SR-BII
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Balreira A, Gaspar P, Caiola D, Chaves J, Beirao I, Lima JL, Azevedo JE, Miranda MC. A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome. Hum Mol Genet. 2008 Jul 15;17(14):2238-43. doi: 10.1093/hmg/ddn124. Epub 2008 Apr 17. Citation on PubMed
- Berkovic SF, Dibbens LM, Oshlack A, Silver JD, Katerelos M, Vears DF, Lullmann-Rauch R, Blanz J, Zhang KW, Stankovich J, Kalnins RM, Dowling JP, Andermann E, Andermann F, Faldini E, D'Hooge R, Vadlamudi L, Macdonell RA, Hodgson BL, Bayly MA, Savige J, Mulley JC, Smyth GK, Power DA, Saftig P, Bahlo M. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am J Hum Genet. 2008 Mar;82(3):673-84. doi: 10.1016/j.ajhg.2007.12.019. Epub 2008 Feb 28. Citation on PubMed or Free article on PubMed Central
- Dang M, Wang X, Wang Q, Wang Y, Lin J, Sun Y, Li X, Zhang L, Lou Z, Wang J, Rao Z. Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71. Protein Cell. 2014 Sep;5(9):692-703. doi: 10.1007/s13238-014-0087-3. Epub 2014 Jul 2. Citation on PubMed or Free article on PubMed Central
- Dibbens LM, Michelucci R, Gambardella A, Andermann F, Rubboli G, Bayly MA, Joensuu T, Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, Berkovic SF. SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure. Ann Neurol. 2009 Oct;66(4):532-6. doi: 10.1002/ana.21765. Citation on PubMed
- Gonzalez A, Valeiras M, Sidransky E, Tayebi N. Lysosomal integral membrane protein-2: a new player in lysosome-related pathology. Mol Genet Metab. 2014 Feb;111(2):84-91. doi: 10.1016/j.ymgme.2013.12.005. Epub 2013 Dec 11. Citation on PubMed or Free article on PubMed Central
- Schroen B, Leenders JJ, van Erk A, Bertrand AT, van Loon M, van Leeuwen RE, Kubben N, Duisters RF, Schellings MW, Janssen BJ, Debets JJ, Schwake M, Hoydal MA, Heymans S, Saftig P, Pinto YM. Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy. J Exp Med. 2007 May 14;204(5):1227-35. doi: 10.1084/jem.20070145. Epub 2007 May 7. Citation on PubMed or Free article on PubMed Central
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