IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database

Hum Mutat. 2013 Oct;34(10):1329-39. doi: 10.1002/humu.22380. Epub 2013 Aug 8.


IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and IL-23 signaling. IL-12Rβ1 deficiency is caused by bi-allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL-12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL-12Rβ1 protein. In addition to disease-causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database ( In this article, we review the function of IL-12Rβ1 and molecular genetics of human IL12RB1.

Keywords: IL-12Rβ1 deficiency; IL12RB1; Mendelian susceptibility to mycobacterial disease.

Publication types

  • Review

MeSH terms

  • Databases, Genetic*
  • Founder Effect
  • Genes, Recessive
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Mutation*
  • Penetrance
  • Polymorphism, Genetic
  • Receptors, Interleukin-12 / deficiency*
  • Receptors, Interleukin-12 / genetics*
  • Receptors, Interleukin-12 / metabolism


  • IL12RB1 protein, human
  • Receptors, Interleukin-12