Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11

An Erratum to this article was published on 01 February 2008


The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Identification and characterization of TTBK2 mutations.
Figure 2: In situ hybridization and immunohistochemistry.


  1. Schols, L. et al. Lancet Neurol. 3, 291–304 (2004).

    Article  Google Scholar 

  2. Harding, A.E. Brain 105, 1–28 (1982).

    Article  CAS  Google Scholar 

  3. Ranum, L.P. & Day, J.W. Curr. Opin. Genet. Dev. 12, 266–271 (2002).

    Article  CAS  Google Scholar 

  4. Orr, H.T. & Zoghbi, H.Y. Annu. Rev. Neurosci. 30, 575–621 (2007).

    Article  CAS  Google Scholar 

  5. Worth, P.F. et al. Am. J. Hum. Genet. 65, 420–426 (1999).

    Article  CAS  Google Scholar 

  6. Baker, M. et al. Nature 442, 916–919 (2006).

    Article  CAS  Google Scholar 

  7. Riudavets, M.A. et al. J. Neuropathol. Exp. Neurol. 65, 1143–1148 (2006).

    Article  Google Scholar 

  8. Mann, D.M. et al. Neuropathol. Appl. Neurobiol. 16, 17–25 (1990).

    Article  CAS  Google Scholar 

  9. Mukaetova-Ladinska, E.B. et al. Am. J. Pathol. 143, 565–578 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Ballatore, C., Lee, V.M. & Trojanowski, J.Q. Nat. Rev. Neurosci. 8, 663–672 (2007).

    Article  CAS  Google Scholar 

  11. Takahashi, M. et al. FEBS Lett. 372, 59–64 (1995).

    Article  CAS  Google Scholar 

  12. Sato, S. et al. J. Neurochem. 98, 1573–1584 (2006).

    Article  CAS  Google Scholar 

  13. Kitano-Takahashi, M. et al. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 63, 602–604 (2007).

    Article  CAS  Google Scholar 

  14. Noble, W. et al. Proc. Natl. Acad. Sci. USA 102, 6990–6995 (2005).

    Article  CAS  Google Scholar 

  15. Kraemer, B.C. et al. Hum. Mol. Genet. 15, 1483–1496 (2006).

    Article  CAS  Google Scholar 

Download references


We are grateful to the UK Medical Research Council (MRC) for their support of the entire project: H.H. holds an MRC clinician scientist fellowship. We also thank the European Commission (EUROSCA) for supporting the initial work. This work was undertaken at University College London Hospital/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centers funding scheme. This work was supported in part by the Intramural Program of the US National Institute on Aging, National Institutes of Health, Department of Health and Human Services. We thank S. Schorge for her helpful comments on the paper as well as the members of the affected families that we studied and the organization Ataxia UK for their continued support and assistance with our work.

Author information

Authors and Affiliations



H.H. planned and supervised the project. J.J. carried out the candidate gene sequencing and genetic analysis. C.G.-T., P.W., P.G. and N.W.W. performed phenotypic assessment of family members. P.W. and M.B.D. carried out the genetic linkage analysis. T.L. and H.H. carried out the in situ hybridization. T.L. prepared the pathology material to be analyzed by D.A.H., J.H. and T.R. D.H. and A.B.S. contributed to the writing of the manuscript and carried out whole-genome arrays. H.H. and N.W.W. wrote the manuscript.

Corresponding authors

Correspondence to Henry Houlden or Nicholas W Wood.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Figures 1–5 and Supplementary Tables 1 and 2 (PDF 987 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Houlden, H., Johnson, J., Gardner-Thorpe, C. et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet 39, 1434–1436 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing