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Gene Review

IL12RB1  -  interleukin 12 receptor, beta 1

Homo sapiens

Synonyms: CD212, IL-12 receptor beta component, IL-12 receptor subunit beta-1, IL-12R subunit beta-1, IL-12R-BETA1, ...
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Disease relevance of IL12RB1

  • This is illustrated by patients with unusual severe infections caused by poorly pathogenic mycobacteria and Salmonella species, in whom genetic deficiencies have been identified in several key genes in the type-1 cytokine pathway, including IL12RB1, the gene encoding the beta1 chain of the IL-12 and IL-23 receptors [1].
  • In conclusion, missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14 M), and 1443 T/C (L467P) of the IFNGR1 encoding genes have no association with the susceptibility to lepromatous leprosy in the Korean population [2].
  • It also reveals that the dysfunction in IL-12R expression seen in cells from HIV(+) patients occurs at the transcriptional level [3].
  • Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes [4].
  • A comprehensive genetic study of IL12RB1 was conducted among 101 Moroccan families, including 157 offspring (age, >15 years) who had culture-positive pulmonary tuberculosis (PTB) [5].

High impact information on IL12RB1

  • Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12 [6].
  • IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells [6].
  • CT inhibited the production of IFN-gamma by anti-CD3-stimulated human peripheral blood mononuclear cell, due in part to suppression of IL-12 production, but also to the inhibition of expression of the beta1 and beta2 chains of the IL-12 receptor on T cells [7].
  • Interestingly, Ba/F3 cells transfected with IL-12R beta 2 alone proliferated in response to huIL-12 with an ED50 of about 50 pM, although a role for endogenous mouse IL-12R beta 1 in IL-12 signal transduction in these transfectants cannot be ruled out [8].
  • When coexpressed in COS-7 cells with the previously identified IL-12 beta receptor (IL-12R beta) protein, two classes of 125I-huIL-12 binding sites were measured with Kds of about 55 pM and 8 nM, corresponding to the high- and low-affinity binding sites seen on phytohemagglutinin-activated lymphoblasts [8].

Biological context of IL12RB1


Anatomical context of IL12RB1

  • Here, in human primary B cells, we found a functional IL-12 receptor (IL-12R) that internalizes following IL-12 binding [11].
  • IL-12 responsiveness and expression of IL-12 receptor in human peripheral blood monocyte-derived dendritic cells [12].
  • Expression of IL-12 and the IL-12 receptor beta1 (IL-12Rbeta1) and IL-12Rbeta2 subunits are suppressed in the spleens of LPS-tolerant mice [13].
  • NK cells from cancer patients who received low-dose IL-2 treatment also exhibited increased expression of IL-12 receptor chains, suggesting that IL-2 may enhance the response to IL-12 in vivo [14].
  • Transfection of a human embryonal kidney cell line 293 (HEKC293) with wild-type IL-12Rbeta1wt gene led to cell surface IL-12Rbeta1 expression; however, no expression was seen in HEKC293 transfected with the mutated IL-12Rbeta1R213W gene [15].

Associations of IL12RB1 with chemical compounds


Physical interactions of IL12RB1


Regulatory relationships of IL12RB1


Other interactions of IL12RB1

  • Complete IL-12 p40 and IL-12 receptor beta1 deficiencies and partial IFNgamma receptor 1 (IFNgammaR1) and IFNgammaR2 deficiencies generally lead to curable infections at various ages, and antibiotics supplemented with IFNgamma if required are likely to be effective [24].
  • However, examination of mRNA showed that both IL-12R beta 1 and IL-12R beta 2 mRNAs were markedly reduced in HIV(+) PBMCs when compared with HIV(-) PBMCs [3].
  • After mitogen activation there was an increase in IL-12R beta 1 expression on the cell surface of HIV(+) and HIV(-) PBMCs and this level was not altered by coculture with rhIL-12 or interferon gamma (IFN-gamma) [3].
  • The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4 [25].
  • Interleukin (IL)-12 production and IL-12 receptor (IL-12R) beta2 chain expression were investigated in patients with allergic asthma successfully treated with rush immunotherapy (RIT) and control patients with mild allergic asthma [26].

Analytical, diagnostic and therapeutic context of IL12RB1

  • Examination of resting PBMCs from HIV(+) and HIV(-) donors showed that neither of these populations expressed IL-12R beta 1 or IL-12R beta 2 chains on their cell surface as detected by flow cytometry [3].
  • Examination at the message level showed a correction of IL-12R beta 1 to normal levels with activation that was further enhanced by rhIL-12 coculture for both the HIV(+) and HIV(-) PBMCs [3].
  • These results indicate that the biological defects of T cells from patients carrying IL-12Rbeta1 deficiency can be corrected by gene transfer and form the basis for further development of gene therapy for this disease [27].
  • Sequence analysis of the cDNA of IL-12R beta(2) revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-gamma production following IL-12 stimulation was under the detection limit [28].
  • Human mutations in IFN-gamma receptor-1 (IFN-gammaR1), IFN-gammaR2, IL-12p40, IL-12 receptor-beta1, signal transducer and activator of transcription-1, and nuclear factor-kappaB essential modulator are analyzed in the context of genetic susceptibility to mycobacterial diseases [29].


  1. Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function. van de Vosse, E., Lichtenauer-Kaligis, E.G., van Dissel, J.T., Ottenhoff, T.H. Immunogenetics (2003) [Pubmed]
  2. Missense mutations of the interleukin-12 receptor beta 1(IL12RB1) and interferon-gamma receptor 1 (IFNGR1) genes are not associated with susceptibility to lepromatous leprosy in Korea. Lee, S.B., Kim, B.C., Jin, S.H., Park, Y.G., Kim, S.K., Kang, T.J., Chae, G.T. Immunogenetics (2003) [Pubmed]
  3. Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear cells from HIV-seropositive individuals is associated with interleukin 12 receptor beta 2 upregulation. Jones, M.L., Young, J.M., Huang, Q.R., Puls, R.L., Webber, C.A., Benson, E.M. AIDS Res. Hum. Retroviruses (2003) [Pubmed]
  4. Association of the IL12RB1 promoter polymorphisms with increased risk of atopic dermatitis and other allergic phenotypes. Takahashi, N., Akahoshi, M., Matsuda, A., Ebe, K., Inomata, N., Obara, K., Hirota, T., Nakashima, K., Shimizu, M., Tamari, M., Doi, S., Miyatake, A., Enomoto, T., Nakashima, H., Ikezawa, Z., Shirakawa, T. Hum. Mol. Genet. (2005) [Pubmed]
  5. Association of IL12RB1 polymorphisms with pulmonary tuberculosis in adults in Morocco. Remus, N., El Baghdadi, J., Fieschi, C., Feinberg, J., Quintin, T., Chentoufi, M., Schurr, E., Benslimane, A., Casanova, J.L., Abel, L. J. Infect. Dis. (2004) [Pubmed]
  6. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. de Jong, R., Altare, F., Haagen, I.A., Elferink, D.G., Boer, T., van Breda Vriesman, P.J., Kabel, P.J., Draaisma, J.M., van Dissel, J.T., Kroon, F.P., Casanova, J.L., Ottenhoff, T.H. Science (1998) [Pubmed]
  7. Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1 and beta2 chain expression. Braun, M.C., He, J., Wu, C.Y., Kelsall, B.L. J. Exp. Med. (1999) [Pubmed]
  8. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Presky, D.H., Yang, H., Minetti, L.J., Chua, A.O., Nabavi, N., Wu, C.Y., Gately, M.K., Gubler, U. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. A novel form of complete IL-12/IL-23 receptor beta1 deficiency with cell surface-expressed nonfunctional receptors. Fieschi, C., Bosticardo, M., de Beaucoudrey, L., Boisson-Dupuis, S., Feinberg, J., Santos, O.F., Bustamante, J., Levy, J., Candotti, F., Casanova, J.L. Blood (2004) [Pubmed]
  10. Influence of interleukin-12 receptor beta1 polymorphisms on tuberculosis. Akahoshi, M., Nakashima, H., Miyake, K., Inoue, Y., Shimizu, S., Tanaka, Y., Okada, K., Otsuka, T., Harada, M. Hum. Genet. (2003) [Pubmed]
  11. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Durali, D., de Goër de Herve, M.G., Giron-Michel, J., Azzarone, B., Delfraissy, J.F., Taoufik, Y. Blood (2003) [Pubmed]
  12. IL-12 responsiveness and expression of IL-12 receptor in human peripheral blood monocyte-derived dendritic cells. Nagayama, H., Sato, K., Kawasaki, H., Enomoto, M., Morimoto, C., Tadokoro, K., Juji, T., Asano, S., Takahashi, T.A. J. Immunol. (2000) [Pubmed]
  13. Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice. Varma, T.K., Toliver-Kinsky, T.E., Lin, C.Y., Koutrouvelis, A.P., Nichols, J.E., Sherwood, E.R. Infect. Immun. (2001) [Pubmed]
  14. Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Wang, K.S., Frank, D.A., Ritz, J. Blood (2000) [Pubmed]
  15. Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Sakai, T., Matsuoka, M., Aoki, M., Nosaka, K., Mitsuya, H. Blood (2001) [Pubmed]
  16. Depressed IL-12-mediated signal transduction in T cells from patients with Sézary syndrome is associated with the absence of IL-12 receptor beta 2 mRNA and highly reduced levels of STAT4. Showe, L.C., Fox, F.E., Williams, D., Au, K., Niu, Z., Rook, A.H. J. Immunol. (1999) [Pubmed]
  17. Direct interaction of STAT4 with the IL-12 receptor. Yao, B.B., Niu, P., Surowy, C.S., Faltynek, C.R. Arch. Biochem. Biophys. (1999) [Pubmed]
  18. Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19. Tello-Ruiz, M.K., Curley, C., DelMonte, T., Giallourakis, C., Kirby, A., Miller, K., Wild, G., Cohen, A., Langelier, D., Latiano, A., Wedemeyer, N., Lander, E., Schreiber, S., Annese, V., Daly, M.J., Rioux, J.D. Eur. J. Hum. Genet. (2006) [Pubmed]
  19. Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. Wu, C.Y., Wang, K., McDyer, J.F., Seder, R.A. J. Immunol. (1998) [Pubmed]
  20. Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity. Ling, P., Gately, M.K., Gubler, U., Stern, A.S., Lin, P., Hollfelder, K., Su, C., Pan, Y.C., Hakimi, J. J. Immunol. (1995) [Pubmed]
  21. IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Elser, B., Lohoff, M., Kock, S., Giaisi, M., Kirchhoff, S., Krammer, P.H., Li-Weber, M. Immunity (2002) [Pubmed]
  22. Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation. Han, P., Hodge, G. Br. J. Haematol. (1999) [Pubmed]
  23. Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7. Monteleone, G., Parrello, T., Luzza, F., Pallone, F. Gut (1998) [Pubmed]
  24. Impaired interferon gamma-mediated immunity and susceptibility to mycobacterial infection in childhood. Remus, N., Reichenbach, J., Picard, C., Rietschel, C., Wood, P., Lammas, D., Kumararatne, D.S., Casanova, J.L. Pediatr. Res. (2001) [Pubmed]
  25. Mutations of the IL-12 receptor beta2 chain gene in atopic subjects. Matsui, E., Kaneko, H., Fukao, T., Teramoto, T., Inoue, R., Watanabe, M., Kasahara, K., Kondo, N. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  26. Allergen rush immunotherapy increases interleukin (IL)-12 production and IL-12 receptor beta2 chain expression in patients with allergic asthma. Tazaki, T., Minoguchi, K., Yokoe, T., Oda, N., Hashimoto, T., Tanaka, A., Okada, S., Yamamoto, Y., Watanabe, Y., Adachi, M. Cell. Immunol. (2004) [Pubmed]
  27. Retroviral-mediated gene transfer restores IL-12 and IL-23 signaling pathways in T cells from IL-12 receptor beta1-deficient patients. Bosticardo, M., Witte, I., Fieschi, C., Novelli, F., Casanova, J.L., Candotti, F. Mol. Ther. (2004) [Pubmed]
  28. Reduced interferon-gamma production and mutations of the interleukin-12 receptor beta(2) chain gene in atopic subjects. Kondo, N., Matsui, E., Kaneko, H., Fukao, T., Teramoto, T., Inoue, R., Watanabe, M., Kasahara, K., Morimoto, N. Int. Arch. Allergy Immunol. (2001) [Pubmed]
  29. Defects in the interferon-gamma and interleukin-12 pathways. Rosenzweig, S.D., Holland, S.M. Immunol. Rev. (2005) [Pubmed]
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