A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1

Nat Genet. 1997 Oct;17(2):149-53. doi: 10.1038/ng1097-149.


Juvenile nephronophthisis (NPH), an autosomal recessive cystic kidney disease, is the primary genetic cause of chronic renal failure in children. About two thirds of patients with NPH carry a large homozygous deletion at the gene locus NPH1 on 2q13. We here identify a novel gene. NPHP1, which extends over most of this common deletion. The 4.5-kb transcript encodes a protein with an SH3 domain, which is highly conserved throughout evolution. The 11-kb interval between the 3' end of NPHP1 and an inverted repeat containing the distal deletion breakpoint was found to contain the first exon of a second gene, MALL. In patients with a hemizygous deletion of the NPH1 region, additional point mutations were found in NPHP1 but not in MALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Exons
  • Gene Expression
  • Humans
  • Kidney Diseases, Cystic / genetics*
  • Membrane Proteins
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Sequence Tagged Sites
  • src Homology Domains / genetics*


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • DNA Primers
  • DNA, Complementary
  • Membrane Proteins
  • NPHP1 protein, human
  • Proteins

Associated data

  • GENBANK/AF023674