The TREM2 gene provides instructions for making a protein called triggering receptor expressed on myeloid cells 2 (TREM2). As its name suggests, this protein is made in myeloid cells, which are cells produced in bone marrow. The TREM2 protein is found on the cell surface, where it interacts with the protein produced from the TYROBP gene. The TREM2 and TYROBP proteins form a complex that transmits chemical signals to activate the cell.
The TYROBP-TREM2 complex was first identified in the immune system. This complex is involved in the growth and development of several types of immune cells, particularly dendritic cells. The TYROBP-TREM2 complex activates these cells, triggering an inflammatory response to injury or disease.
The TYROBP-TREM2 complex also activates cells in the skeletal system and in the brain and spinal cord (central nervous system). In the skeletal system, the complex is found in osteoclasts, which are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. These cells are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone.
In the central nervous system, the TYROBP-TREM2 complex appears to play an important role in immune cells called microglia. These cells protect the brain and spinal cord from foreign invaders and remove dead nerve cells and other debris. Although the TYROBP-TREM2 complex plays a critical role in osteoclasts and microglia, its exact function in these cells is unclear
Health Conditions Related to Genetic Changes
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
Variants (also called mutations) in the TREM2 gene have been identified in people with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (commonly known as PLOSL). Some variants prevent the cell from making any TREM2 proteins, while others result in the production of an abnormally short, nonfunctional version of the protein. Other variants change the structure of the TREM2 protein, preventing it from reaching the cell surface.
Researchers believe that the signs and symptoms of PLOSL are related to defective TYROBP-TREM2 signaling in osteoclasts and microglia. The bone abnormalities seen in people with this disorder are probably related to malfunctioning osteoclasts, which are less able to resorb bone tissue during bone remodeling. In the central nervous system, defective signaling through the TYROBP-TREM2 complex causes widespread abnormalities of microglia. Researchers are working to determine how these abnormalities lead to the neurological problems associated with PLOSL.More About This Health Condition
Other Names for This Gene
- triggering receptor expressed on monocytes 2
- triggering receptor expressed on myeloid cells 2a
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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- Kiialainen A, Veckman V, Saharinen J, Paloneva J, Gentile M, Hakola P, Hemelsoet D, Ridha B, Kopra O, Julkunen I, Peltonen L. Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response. J Mol Med (Berl). 2007 Sep;85(9):971-83. doi: 10.1007/s00109-007-0191-4. Epub 2007 May 26. Citation on PubMed
- Klunemann HH, Ridha BH, Magy L, Wherrett JR, Hemelsoet DM, Keen RW, De Bleecker JL, Rossor MN, Marienhagen J, Klein HE, Peltonen L, Paloneva J. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology. 2005 May 10;64(9):1502-7. doi: 10.1212/01.WNL.0000160304.00003.CA. Citation on PubMed
- Neumann H, Takahashi K. Essential role of the microglial triggering receptor expressed on myeloid cells-2 (TREM2) for central nervous tissue immune homeostasis. J Neuroimmunol. 2007 Mar;184(1-2):92-9. doi: 10.1016/j.jneuroim.2006.11.032. Epub 2007 Jan 18. Citation on PubMed
- Paloneva J, Mandelin J, Kiialainen A, Bohling T, Prudlo J, Hakola P, Haltia M, Konttinen YT, Peltonen L. DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. J Exp Med. 2003 Aug 18;198(4):669-75. doi: 10.1084/jem.20030027. Citation on PubMed or Free article on PubMed Central
- Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002 Sep;71(3):656-62. doi: 10.1086/342259. Epub 2002 Jun 21. Erratum In: Am J Hum Genet. 2003 Jan;72(1):225. Citation on PubMed or Free article on PubMed Central