NPHS2, Encoding the Glomerular Protein Podocin, Is Mutated in Autosomal Recessive Steroid-Resistant Nephrotic Syndrome

Nat Genet. 2000 Apr;24(4):349-54. doi: 10.1038/74166.

Abstract

Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / genetics
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Expressed Sequence Tags
  • Fetus
  • Genes, Recessive
  • Genetic Linkage
  • Helminth Proteins / genetics
  • Humans
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Kidney Glomerulus / embryology
  • Kidney Glomerulus / metabolism*
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Multigene Family
  • Mutation / genetics*
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / metabolism
  • Organ Specificity
  • Pedigree
  • Physical Chromosome Mapping
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid

Substances

  • Blood Proteins
  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Intracellular Signaling Peptides and Proteins
  • MEC-2 protein, C elegans
  • Membrane Proteins
  • NPHS2 protein
  • STOM protein, human

Associated data

  • GENBANK/AJ279246
  • GENBANK/AJ279247
  • GENBANK/AJ279248
  • GENBANK/AJ279249
  • GENBANK/AJ279250
  • GENBANK/AJ279251
  • GENBANK/AJ279252
  • GENBANK/AJ279253
  • GENBANK/AJ279254