Reviewed November 2008
What is the official name of the TYROBP gene?
The official name of this gene is “TYRO protein tyrosine kinase binding protein.”
TYROBP is the gene's official symbol. The TYROBP gene is also known by other names, listed below.
What is the normal function of the TYROBP gene?
The TYROBP gene (also known as the DAP12 gene) provides instructions for making a protein called the TYRO protein tyrosine kinase binding protein. This protein is found in a variety of cells produced in bone marrow (myeloid cells) and other immune system cells (lymphoid cells). The protein is located on the cell surface, where it helps transmit chemical signals that activate the cell.
The TYROBP protein interacts with several other proteins on the surface of cells. For example, it forms a complex with the protein produced from the TREM2 gene. The TYROBP protein and its partners were first identified in the immune system, where they activate certain cells (such as natural killer cells and dendritic cells) that trigger 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 TYROBP gene related to health conditions?
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy - caused by mutations in the TYROBP gene
At least six mutations in the TYROBP gene have been identified in people with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (commonly known as PLOSL). One TYROBP mutation has been found to cause PLOSL in all affected people of Finnish ancestry. This mutation deletes a significant portion of the TYROBP gene, which prevents the cell from producing any protein from this gene. Mutations in other populations result in the production of an abnormally short, nonfunctional version of the protein or prevent the protein 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 TYROBP gene located?
Cytogenetic Location: 19q13.1
Molecular Location on chromosome 19: base pairs 35,904,400 to 35,908,514
The TYROBP gene is located on the long (q) arm of chromosome 19 at position 13.1.
More precisely, the TYROBP gene is located from base pair 35,904,400 to base pair 35,908,514 on chromosome 19.
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 TYROBP?
You and your healthcare professional may find the following resources about TYROBP 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 TYROBP (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7305%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- OMIM - Genetic disorder catalog (http://omim.org/entry/604142)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_TYROBP.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7305)
- HGNC Gene Symbol Report (http://www.genenames.org/data/hgnc_data.php?hgnc_id=12449)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7305)
What other names do people use for the TYROBP gene or gene products?
- DNAX-activation protein 12
- KAR-associated protein
- killer activating receptor associated protein
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 TYROBP?
bone marrow ;
bone remodeling ;
central nervous system ;
immune system ;
killer cells ;
natural killer cells ;
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)
- Gene Review: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) (http://www.ncbi.nlm.nih.gov/books/NBK1197)
- Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura MC. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004 Feb;19(2):224-34. Epub 2003 Dec 16. (http://www.ncbi.nlm.nih.gov/pubmed/14969392?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)
- Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998 Feb 12;391(6668):703-7. (http://www.ncbi.nlm.nih.gov/pubmed/9490415?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7305)
- Paloneva J, Kestilä M, Wu J, Salminen A, Böhling T, Ruotsalainen V, Hakola P, Bakker AB, Phillips JH, Pekkarinen P, Lanier LL, Timonen T, Peltonen L. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat Genet. 2000 Jul;25(3):357-61. (http://www.ncbi.nlm.nih.gov/pubmed/10888890?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)
- Takaki R, Watson SR, Lanier LL. DAP12: an adapter protein with dual functionality. Immunol Rev. 2006 Dec;214:118-29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17100880?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.