GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans


  • Y. Yao
  • P. Du Jiang
  • B.N. Chao
  • D. Cagdas
  • S. Kubo
  • A. Balasubramaniyam
  • Y. Zhang
  • B. Shadur
  • A. NaserEddin
  • L.R. Folio
  • B. Schwarz
  • E. Bohrnsen
  • L. Zheng
  • M. Lynberg
  • S. Gottlieb
  • M.A. Leney-Greene
  • A.Y. Park
  • I. Tezcan
  • A. Akdogan
  • R. Gocmen
  • S. Onder
  • A. Rosenberg
  • E.J. Soilleux
  • E. Johnson
  • P.K. Jackson
  • J. Demeter
  • S.D. Chauvin
  • F. Paul
  • M. Selbach
  • H. Bulut
  • M.R. Clatworthy
  • Z.K. Tuong
  • H. Zhang
  • B.J. Stewart
  • C.M. Bosio
  • P. Stepensky
  • S. Clare
  • S. Ganesan
  • J.C. Pascall
  • O. Daumke
  • G.W. Butcher
  • A.J. McMichael
  • A.K. Simon
  • M.J. Lenardo


  • Journal of Experimental Medicine


  • J Exp Med 219 (6): e20201405


  • Inborn errors of immunity (IEIs) unveil regulatory pathways of human immunity. We describe a new IEI caused by mutations in the GTPase of the immune-associated protein 6 (GIMAP6) gene in patients with infections, lymphoproliferation, autoimmunity, and multiorgan vasculitis. Patients and Gimap6(-/-) mice show defects in autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)-containing lipids. We find that GIMAP6 complexes with GABARAPL2 and GIMAP7 to regulate GTPase activity. Also, GIMAP6 is induced by IFN-γ and plays a critical role in antibacterial immunity. Finally, we observed that Gimap6(-/-) mice died prematurely from microangiopathic glomerulosclerosis most likely due to GIMAP6 deficiency in kidney endothelial cells.