Reviewed November 2008
What is the official name of the TREM2 gene?
The official name of this gene is “triggering receptor expressed on myeloid cells 2.”
TREM2 is the gene's official symbol. The TREM2 gene is also known by other names, listed below.
What is the normal function of the TREM2 gene?
The TREM2 gene provides instructions for making a protein called triggering receptor expressed on myeloid cells 2. 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 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
How are changes in the TREM2 gene related to health conditions?
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy - caused by mutations in the TREM2 gene
At least 10 mutations in the TREM2 gene have been identified in people with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (commonly known as PLOSL). Some mutations prevent the cell from making any TREM2 protein, while others result in the production of an abnormally short, nonfunctional version of the protein. Still other mutations 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 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.
Where is the TREM2 gene located?
Cytogenetic Location: 6p21.1
Molecular Location on chromosome 6: base pairs 41,158,506 to 41,163,198
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/54209))
The TREM2 gene is located on the short (p) arm of chromosome 6 at position 21.1.
More precisely, the TREM2 gene is located from base pair 41,158,506 to base pair 41,163,198 on chromosome 6.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about TREM2?
You and your healthcare professional may find the following resources about TREM2 helpful.
Educational resources - Information pages
- Basic Neurochemistry (sixth edition, 1998): The microglial cell plays a role in phagocytosis and inflammatory responses (http://www.ncbi.nlm.nih.gov/books/NBK28217/)
- Molecular Biology of the Cell (fourth edition, 2002): Bone is continually remodeled by the cells within it (http://www.ncbi.nlm.nih.gov/books/NBK26889/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1197)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for TREM2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=54209%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28TREM2%5BTIAB%5D%29%20OR%20%28TREM-2%5BTIAB%5D%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/605086)
Research Resources - Tools for researchers
- HGNC Gene Family: V-set domain containing (http://www.genenames.org/cgi-bin/genefamilies/set/590)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=17761)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/54209)
What other names do people use for the TREM2 gene or gene products?
- triggering receptor expressed on monocytes 2
- triggering receptor expressed on myeloid cells 2a
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding TREM2?
bone marrow ;
bone remodeling ;
central nervous system ;
immune system ;
nervous system ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bouchon A, Hernández-Munain C, Cella M, Colonna M. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J Exp Med. 2001 Oct 15;194(8):1111-22. (http://www.ncbi.nlm.nih.gov/pubmed/11602640?dopt=Abstract)
- Cella M, Buonsanti C, Strader C, Kondo T, Salmaggi A, Colonna M. Impaired differentiation of osteoclasts in TREM-2-deficient individuals. J Exp Med. 2003 Aug 18;198(4):645-51. Epub 2003 Aug 11. (http://www.ncbi.nlm.nih.gov/pubmed/12913093?dopt=Abstract)
- Colonna M, Turnbull I, Klesney-Tait J. The enigmatic function of TREM-2 in osteoclastogenesis. Adv Exp Med Biol. 2007;602:97-105. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17966394?dopt=Abstract)
- Colonna M. TREMs in the immune system and beyond. Nat Rev Immunol. 2003 Jun;3(6):445-53. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12776204?dopt=Abstract)
- Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura MC. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006 Feb;21(2):237-45. Epub 2005 Oct 20. (http://www.ncbi.nlm.nih.gov/pubmed/16418779?dopt=Abstract)
- Kiialainen A, Hovanes K, Paloneva J, Kopra O, Peltonen L. Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiol Dis. 2005 Mar;18(2):314-22. (http://www.ncbi.nlm.nih.gov/pubmed/15686960?dopt=Abstract)
- 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. Epub 2007 May 26. (http://www.ncbi.nlm.nih.gov/pubmed/17530208?dopt=Abstract)
- Klünemann 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. (http://www.ncbi.nlm.nih.gov/pubmed/15883308?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/54209)
- 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. Epub 2007 Jan 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17239445?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/12925681?dopt=Abstract)
- 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. Epub 2002 Jun 21. Erratum in: Am J Hum Genet. 2003 Jan;72(1):225.. (http://www.ncbi.nlm.nih.gov/pubmed/12080485?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.