Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

@article{Flannick2014LossoffunctionMI,
  title={Loss-of-function mutations in SLC30A8 protect against type 2 diabetes},
  author={J. Flannick and G. Thorleifsson and N. Beer and S. B. Jacobs and N. Grarup and N. Burtt and A. Mahajan and C. Fuchsberger and G. Atzmon and R. Benediktsson and J. Blangero and D. Bowden and I. Brandslund and J. Brosnan and F. Burslem and J. Chambers and Y. S. Cho and C. Christensen and Desir{\'e}e A. Douglas and R. Duggirala and Zachary Dymek and Y. Farjoun and T. Fennell and P. Fontanillas and T. Fors{\'e}n and S. Gabriel and B. Glaser and D. Gudbjartsson and C. Hanis and T. Hansen and {\'A}. Hreidarsson and K. Hveem and E. Ingelsson and B. Isomaa and S. Johansson and T. J{\o}rgensen and M. J{\o}rgensen and S. Kathiresan and A. Kong and J. Kooner and Jasmina Kravic and M. Laakso and Jong-Young Lee and L. Lind and C. Lindgren and A. Linneberg and G. M{\'a}sson and T. Meitinger and K. Mohlke and A. Molven and A. Morris and S. Potluri and R. Rauramaa and R. Ribel‐Madsen and A. Richard and T. Rolph and V. Salomaa and Ayellet V. Segr{\`e} and H. Sk{\"a}rstrand and V. Steinthorsdottir and H. Stringham and P. Sulem and E. Tai and Y. Teo and Tanya M. Teslovich and U. Thorsteinsdottir and J. Trimmer and T. Tuomi and J. Tuomilehto and F. Vaziri-Sani and B. Voight and James G. Wilson and M. Boehnke and M. McCarthy and P. Nj{\o}lstad and O. Pedersen and L. Groop and D. Cox and K. Stef{\'a}nsson and D. Altshuler},
  journal={Nature Genetics},
  year={2014},
  volume={46},
  pages={357-363}
}
Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein… Expand
Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms
Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity
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