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Gene Review

Kirrel  -  kin of IRRE like (Drosophila)

Mus musculus

Synonyms: 6720469N11Rik, Kin of IRRE-like protein 1, Kin of irregular chiasm-like protein 1, Kirrel1, Neph1, ...
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Disease relevance of Kirrel1

  • Disruption of the Neph1-nephrin interaction in vivo by injecting combinations of individual subnephritogenic doses of anti-Neph1 and anti-nephrin results in complement- and leukocyte-independent proteinuria with preserved foot processes [1].
  • Neph1-deficient mice develop nephrotic syndrome at birth, indicating the importance of this protein in the development of a normal glomerular filtration barrier [1].
  • The Neph1(-/-) animals that survived beyond the first week of life were sickly and small but without edema, and all died between 3 and 8 weeks of age [2].

High impact information on Kirrel1


Chemical compound and disease context of Kirrel1

  • The importance of several of them (nephrin, podocin, CD2AP, and Neph1) in the maintenance of the glomerular filtration barrier has been demonstrated by the occurrence of massive proteinuria when they are defective [4].

Associations of Kirrel1 with chemical compounds

  • Here it colocalizes with the synaptic scaffolder calmodulin-associated serin/threonin kinase (CASK), and both Neph1 and Neph2 interact with the PDZ domain of CASK via their cytoplasmic tail [5].

Analytical, diagnostic and therapeutic context of Kirrel1

  • In this paper, we localize the expression of Neph1 to the glomerular slit diaphragm by immunogold electron microscopy in rodents and describe its direct interaction with two other components of the slit diaphragm, nephrin and ZO-1 [1].
  • While the precise subcellular localization of Neph1 remains unknown, its relationship with other components of the glomerular filtration barrier is of great interest in this field [1].
  • Neph1 migrated as a 90-kDa protein on SDS-PAGE under reducing conditions [3].


  1. Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability. Liu, G., Kaw, B., Kurfis, J., Rahmanuddin, S., Kanwar, Y.S., Chugh, S.S. J. Clin. Invest. (2003) [Pubmed]
  2. Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Donoviel, D.B., Freed, D.D., Vogel, H., Potter, D.G., Hawkins, E., Barrish, J.P., Mathur, B.N., Turner, C.A., Geske, R., Montgomery, C.A., Starbuck, M., Brandt, M., Gupta, A., Ramirez-Solis, R., Zambrowicz, B.P., Powell, D.R. Mol. Cell. Biol. (2001) [Pubmed]
  3. Nephrin and Neph1 co-localize at the podocyte foot process intercellular junction and form cis hetero-oligomers. Barletta, G.M., Kovari, I.A., Verma, R.K., Kerjaschki, D., Holzman, L.B. J. Biol. Chem. (2003) [Pubmed]
  4. Podocyte differentiation and hereditary proteinuria/nephrotic syndromes. Gubler, M.C. J. Am. Soc. Nephrol. (2003) [Pubmed]
  5. Neuronal expression and interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis. Gerke, P., Benzing, T., Höhne, M., Kispert, A., Frotscher, M., Walz, G., Kretz, O. J. Comp. Neurol. (2006) [Pubmed]
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