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Chen, H. TYROBP Gene. Encyclopedia. Available online: (accessed on 20 June 2024).
Chen H. TYROBP Gene. Encyclopedia. Available at: Accessed June 20, 2024.
Chen, Hongliu. "TYROBP Gene" Encyclopedia, (accessed June 20, 2024).
Chen, H. (2020, December 23). TYROBP Gene. In Encyclopedia.
Chen, Hongliu. "TYROBP Gene." Encyclopedia. Web. 23 December, 2020.

TYRO protein tyrosine kinase binding protein.


1. Normal Function

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.

2. Health Conditions Related to Genetic Changes

2.1. Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy

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.

3. Other Names for This Gene

  • DAP12

  • DNAX-activation protein 12

  • KAR-associated protein


  • killer activating receptor associated protein



  1. Bouchon A, Hernández-Munain C, Cella M, Colonna M. A DAP12-mediated pathwayregulates expression of CC chemokine receptor 7 and maturation of human dendriticcells. J Exp Med. 2001 Oct 15;194(8):1111-22.
  2. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL,Nakamura MC. The signaling adapter protein DAP12 regulates multinucleation duringosteoclast development. J Bone Miner Res. 2004 Feb;19(2):224-34.
  3. 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.
  4. Kiialainen A, Veckman V, Saharinen J, Paloneva J, Gentile M, Hakola P,Hemelsoet D, Ridha B, Kopra O, Julkunen I, Peltonen L. Transcript profiles ofdendritic cells of PLOSL patients link demyelinating CNS disorders withabnormalities in pathways of actin bundling and immune response. J Mol Med(Berl). 2007 Sep;85(9):971-83.
  5. Klünemann HH, Ridha BH, Magy L, Wherrett JR, Hemelsoet DM, Keen RW, DeBleecker JL, Rossor MN, Marienhagen J, Klein HE, Peltonen L, Paloneva J. Thegenetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12and TREM2. Neurology. 2005 May 10;64(9):1502-7.
  6. Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12bearing a tyrosine-based activation motif is involved in activating NK cells.Nature. 1998 Feb 12;391(6668):703-7.
  7. Paloneva J, Autti T, Hakola P, Haltia MJ. Polycystic LipomembranousOsteodysplasia with Sclerosing Leukoencephalopathy. 2002 Jan 24 [updated 2020 Dec10]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available from
  8. 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.
  9. Paloneva J, Mandelin J, Kiialainen A, Bohling T, Prudlo J, Hakola P, Haltia M,Konttinen YT, Peltonen L. DAP12/TREM2 deficiency results in impaired osteoclastdifferentiation and osteoporotic features. J Exp Med. 2003 Aug 18;198(4):669-75.
  10. Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R,Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, PeltonenL. Mutations in two genes encoding different subunits of a receptor signalingcomplex result in an identical disease phenotype. Am J Hum Genet. 2002Sep;71(3):656-62.Jan;72(1):225..
  11. Takaki R, Watson SR, Lanier LL. DAP12: an adapter protein with dualfunctionality. Immunol Rev. 2006 Dec;214:118-29. Review.
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