Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)

Nature. 1995 Sep 7;377(6544):65-8. doi: 10.1038/377065a0.


Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • Base Sequence
  • Cell Line, Transformed
  • DNA Mutational Analysis
  • DNA Primers
  • Humans
  • Janus Kinase 3
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics*
  • Sequence Deletion
  • Severe Combined Immunodeficiency / enzymology
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / immunology
  • T-Lymphocytes / immunology


  • DNA Primers
  • Protein-Tyrosine Kinases
  • JAK3 protein, human
  • Janus Kinase 3

Associated data

  • GENBANK/U09607