Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis--a review

Eur J Pediatr. 2009 Nov;168(11):1291-304. doi: 10.1007/s00431-009-1017-x. Epub 2009 Jun 27.


This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin beta2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction.

Publication types

  • Review

MeSH terms

  • Actinin / genetics
  • Adaptor Proteins, Signal Transducing / genetics
  • Cytoskeletal Proteins / genetics
  • Genetic Markers / genetics*
  • Genome
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Glomerulosclerosis, Focal Segmental / physiopathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney Glomerulus / physiopathology*
  • Laminin / genetics
  • Membrane Proteins / genetics
  • Mutation
  • Phosphoinositide Phospholipase C / genetics
  • Podocytes*
  • Proteinuria / genetics
  • TRPC Cation Channels / genetics
  • TRPC6 Cation Channel
  • WT1 Proteins / genetics


  • ACTN4 protein, human
  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Cytoskeletal Proteins
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • Laminin
  • Membrane Proteins
  • NPHS2 protein
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • WT1 Proteins
  • nephrin
  • Actinin
  • laminin beta2
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon