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Tbio Interleukin-12 receptor subunit beta-2

Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production.

The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

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Property Summary

NCBI Gene PubMed Count 79
PubMed Score 29.58
PubTator Score 46.80

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count
Behcet Syndrome 23
Disease Target Count Z-score Confidence
Primary biliary cirrhosis 45 3.706 1.9

Expression

  Differential Expression (13)

Disease log2 FC p
cutaneous lupus erythematosus 1.300 1.3e-02
posterior fossa group A ependymoma -1.300 1.3e-06
glioblastoma -1.500 1.4e-03
atypical teratoid / rhabdoid tumor -1.500 6.8e-05
medulloblastoma -1.400 6.9e-04
primitive neuroectodermal tumor -1.700 4.5e-03
Atopic dermatitis 1.100 2.3e-03
cystic fibrosis 1.100 1.1e-03
pediatric high grade glioma -1.100 3.5e-03
pilocytic astrocytoma -1.200 1.4e-03
psoriasis 1.900 1.6e-115
pulmonary arterial hypertension -2.500 4.5e-02
acute myeloid leukemia -2.500 3.3e-03

Synonym

Accession Q99665 B1AN98 B7ZKL9 F5H7L6 Q2M3V3 IL-12 receptor subunit beta-2
Symbols

Gene

IL12RB2

PANTHER Protein Class (3)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (13)

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 GO Function (1)

 GO Component (3)

 GO Process (6)

 Compartment GO Term (17)

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 IMPC Phenotype (1)

 MGI Phenotype (9)

 GWAS Trait (2)

 HCA RNA Cell Line (52)

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Pathway (18)

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Protein-protein Interaction (3)

IL6ST   EBI3   HLA-A  

Gene RIF (62)

PMID Text
26552659 The effects of rs3762315 and rs3762316 single nucleotide polymorphisms in 5' flanking region on IL12RB2 transcription
26547104 IL12RB2 polymorphisms correlate with risk of lung adenocarcinoma.
25720506 IL12RB2 polymorphism is associated with systemic lupus erythematosus in the Chinese population.
25695486 Estrogen receptor beta 2 regulates IL12RB2 expression via p38 MAPK signaling and inhibits non-small-cell lung cancer proliferation and invasion.
24859272 Genetic variations of IL-12B, IL-12Rbeta1, IL-12Rbeta2 in Behcet's disease and VKH syndrome.
24486579 Polymorphisms present in the promoter region of IL12RB2 may not be associated with susceptibility to leprosy or its clinical forms.
24434271 results suggest the rs924080 risk A allele does not affect baseline expression of IL-12RB2, IL-23R, IFN-gamma and TNF-alpha but enhances IL-23R and TNF-alpha expression capacity in response to LPS stimulation; the A allele appears to enhance baseline IL-6 production
23911393 Data indicate that four of the IL-12Rbeta2 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant.
23677568 ERbeta2 and IL-12Rbeta5 had longer OS.
23152861 Association of IL12RB2 rs6679356 polymorphism with the age of type 1 diabetes mellitus onset suggests that this gene plays a role in defining the time of disease onset.
23009887 Data indicate that SNP (rs452204) in the IL1RN gene was significantly associated with higher levels of IL-2 secretion, and IL12RB2 SNP rs3790567 was associated with a decrease in IL-1beta secretion.
22715389 a differential regulation pattern for genes solely expressed in Th17 cells (IL17A and CCL20) compared to genes expressed in both Th17 and Th1 cells (IL23R and IL12RB2), where high levels of promoter methylation are correlated to near zero
22509293 the -237 polymorphic site in the 5' promoter region of the IL-12Rbeta2 (SNP ID: rs11810249) gene associated with the AP-4 transcription motif GAGCTG
22378604 Variants in IL10 and IL23R-IL12RB2 are associated with Behcet's disease in Iranian patients.
22076442 data clearly support the IL12RB2 genetic association with systemic sclerosis (SSc), and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
21285166 Our results support a potential influence of the rs3790567 IL12RB2 polymorphism in the pathogenesis of giant cell arteritis.
20716621 Observational study of gene-disease association. (HuGE Navigator)
20673868 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20622879 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
20622878 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
20568250 Observational study of gene-disease association. (HuGE Navigator)
20525402 Observational study of gene-disease association. (HuGE Navigator)
20503287 Observational study of gene-disease association. (HuGE Navigator)
20452482 Observational study of gene-disease association. (HuGE Navigator)
20424473 Observational study of gene-disease association. (HuGE Navigator)
20350312 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
20060272 significant interaction between the IL-12RB1 and IL-12RB2 genes contributes to a 4-fold increased risk for developing extrinsic atopic dermatitis
20060272 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19773279 Observational study of gene-disease association. (HuGE Navigator)
19720917 Studies established the concept that the IL-12Rbeta2 gene is a gatekeeper from cancer.
19604093 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
19573080 Observational study of gene-disease association. (HuGE Navigator)
19458352 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19458352 Our data show significant associations between primary biliary cirrhosis and common genetic variants at the HLA class II, IL12A, and IL12RB2 loci
19258923 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
18927311 Single Nucleotide Polymorphism in interleukin 12 receptor beta 2 is associated with susceptibility to radiation dermatitis in breast cancer.
18927311 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18771340 These results suggest that these SNPs in IL12RB2 have differential effects on cellular activation of T cells and NK cells.
18715339 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18474725 IL-12R beta 2 directly restrains multiple myeloma cell growth
18353079 frequencies of variant alleles were significantly higher in aggressive periodontitis patients as compared with healthy controls or chronic periodontitis patients
18353079 Observational study of gene-disease association. (HuGE Navigator)
17703412 Observational study of gene-disease association. (HuGE Navigator)
17622942 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17602269 Epigenetic silencing of IL-12Rbeta2 is a frequent event in lung cancers. Aberrant methylation of this gene seems to be a useful predictor of long-term outcome for adenocarcinoma of the lung.
17236132 Observational study of gene-disease association. (HuGE Navigator)
17152005 Observational study of gene-disease association. (HuGE Navigator)
15976343 Observational study of gene-disease association. (HuGE Navigator)
15901746 Study showed recombinant human interleukin-12 (rhIL-12) safe/well tolerated in healthy subjects given single doses (1 up to 8 ug) subcutaneously. Interferon-gamma and, signal transducer and activator of transcription may be useful biomarkers of rhIL-12.
15140029 Observational study of gene-disease association. (HuGE Navigator)
15140029 promoter activity is increased in case of the -465G allele, disrupting the intact GATA site
15004750 Observational study of gene-disease association. (HuGE Navigator)
12804004 upregulated in Il-12 augmented T cell activation of mononclear leukocytes from HIV seropositive individuals
12768436 Observational study of genotype prevalence. (HuGE Navigator)
12743658 Observational study of gene-disease association. (HuGE Navigator)
12719941 Observational study of gene-disease association. (HuGE Navigator)
11940489 STATE OF ART REVIEW. IL-12Rb2 gene is not expressed in EBV-transformed normal B-lymphocytes and in Burkitt's lymphoma B-cell lines.
11441083 In the generation of cell-mediated immunity against intracellular infection, the expression and function of the IL-12 receptor beta 2 chain correlate with the response of Th1-type cells to Mycobacterium leprae antigen.
11306945 Observational study of gene-disease association. (HuGE Navigator)

AA Sequence 

MAHTFRGCSLAFMFIITWLLIKAKIDACKRGDVTVKPSHVILLGSTVNITCSLKPRQGCFHYSRRNKLIL      1 - 70
YKFDRRINFHHGHSLNSQVTGLPLGTTLFVCKLACINSDEIQICGAEIFVGVAPEQPQNLSCIQKGEQGT     71 - 140
VACTWERGRDTHLYTEYTLQLSGPKNLTWQKQCKDIYCDYLDFGINLTPESPESNFTAKVTAVNSLGSSS    141 - 210
SLPSTFTFLDIVRPLPPWDIRIKFQKASVSRCTLYWRDEGLVLLNRLRYRPSNSRLWNMVNVTKAKGRHD    211 - 280
LLDLKPFTEYEFQISSKLHLYKGSWSDWSESLRAQTPEEEPTGMLDVWYMKRHIDYSRQQISLFWKNLSV    281 - 350
SEARGKILHYQVTLQELTGGKAMTQNITGHTSWTTVIPRTGNWAVAVSAANSKGSSLPTRINIMNLCEAG    351 - 420
LLAPRQVSANSEGMDNILVTWQPPRKDPSAVQEYVVEWRELHPGGDTQVPLNWLRSRPYNVSALISENIK    421 - 490
SYICYEIRVYALSGDQGGCSSILGNSKHKAPLSGPHINAITEEKGSILISWNSIPVQEQMGCLLHYRIYW    491 - 560
KERDSNSQPQLCEIPYRVSQNSHPINSLQPRVTYVLWMTALTAAGESSHGNEREFCLQGKANWMAFVAPS    561 - 630
ICIAIIMVGIFSTHYFQQKVFVLLAALRPQWCSREIPDPANSTCAKKYPIAEEKTQLPLDRLLIDWPTPE    631 - 700
DPEPLVISEVLHQVTPVFRHPPCSNWPQREKGIQGHQASEKDMMHSASSPPPPRALQAESRQLVDLYKVL    701 - 770
ESRGSDPKPENPACPWTVLPAGDLPTHDGYLPSNIDDLPSHEAPLADSLEELEPQHISLSVFPSSSLHPL    771 - 840
TFSCGDKLTLDQLKMRCDSLML                                                    841 - 862
//

Text Mined References (80)

PMID Year Title
26552659 2016 Functional analysis of differences in transcriptional activity conferred by genetic variants in the 5' flanking region of the IL12RB2 gene.
26547104 2016 IL12RB2 Polymorphisms correlate with risk of lung adenocarcinoma.
25720506 2015 Autoimmune risk loci of IL12RB2, IKZF1, XKR6, TMEM39A and CSK in Chinese patients with systemic lupus erythematosus.
25695486 2015 Estrogen receptor?2 regulates interlukin-12 receptor?2 expression via p38 mitogen-activated protein kinase signaling and inhibits non-small-cell lung cancer proliferation and invasion.
24859272 2014 Genetic variations of IL-12B, IL-12R?1, IL-12R?2 in Behcet's disease and VKH syndrome.
24486579 2014 Polymorphisms assessment in the promoter region of IL12RB2 in Amazon leprosy patients.
24434271 2014 Increased IL-23 receptor, TNF-? and IL-6 expression in individuals with the IL23R-IL12RB2 locus polymorphism.
23911393 2013 Differential expression and function of human IL-12R?2 polymorphic variants.
23677568 2013 The co-expression of ER?2 and IL-12R?2 is better prognostic factor in non-small-cell lung cancer progression.
23152861 2012 IL12RB2 gene is associated with the age of type 1 diabetes onset in Croatian family Trios.
23128233 2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
23009887 2012 Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity after smallpox vaccination.
22715389 2012 Effector CD4+ T cell expression signatures and immune-mediated disease associated genes.
22509293 2012 Prevalence, distribution and functional significance of the -237C to T polymorphism in the IL-12R?2 promoter in Indian tuberculosis patients.
22412388 2012 A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
22378604 2012 Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.
22076442 2012 A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations.
21399635 2011 Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
21285166 2011 Role of rs1343151 IL23R and rs3790567 IL12RB2 polymorphisms in biopsy-proven giant cell arteritis.
20716621 2010 Genetic polymorphisms in adaptive immunity genes and childhood acute lymphoblastic leukemia.
20673868 2010 A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM).
20639880 2010 Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20622879 2010 Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.
20622878 2010 Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease.
20568250 2010 Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.
20525402 2010 Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study.
20503287 2010 Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls.
20452482 2010 Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.
20424473 2010 L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms.
20350312 2010 Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20060272 2010 Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL-12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic dermatitis in Koreans.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19720917 2009 Interleukin-12 receptor beta2: from cytokine receptor to gatekeeper gene in human B-cell malignancies.
19604093 2009 Genetic polymorphisms, their allele combinations and IFN-beta treatment response in Irish multiple sclerosis patients.
19573080 2009 Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
19458352 2009 Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.
19258923 2009 Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.
18927311 2008 IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis.
18771340 2008 Differential effects of polymorphisms in the 5' flanking region of IL12RB2 on NK- and T-cell activity.
18715339 2008 Associations between cytokine/cytokine receptor single nucleotide polymorphisms and humoral immunity to measles, mumps and rubella in a Somali population.
18474725 2008 Constitutive expression of IL-12R beta 2 on human multiple myeloma cells delineates a novel therapeutic target.
18353079 2008 Polymorphisms in the 5' flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population.
17703412 2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.
17622942 2007 Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers.
17602269 2007 Aberrant methylation of IL-12Rbeta2 gene in lung adenocarcinoma cells is associated with unfavorable prognosis.
17236132 2007 A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes.
17152005 2007 Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15976343 2005 Polymorphism of the 5' flanking region of the IL-12 receptor beta2 gene partially determines the clinical types of leprosy through impaired transcriptional activity.
15901746 2005 A single administration of recombinant human interleukin-12 is associated with increased expression levels of interferon-gamma and signal transducer and activator of transcription in healthy subjects.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15140029 2004 A novel polymorphic GATA site in the human IL-12Rbeta2 promoter region affects transcriptional activity.
15004750 2004 Association between IFNA genotype and the risk of sarcoidosis.
14559241 2003 SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit.
12804004 2003 Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear cells from HIV-seropositive individuals is associated with interleukin 12 receptor beta 2 upregulation.
12768436 2003 Characterization of 458 single nucleotide polymorphisms of disease candidate genes in the Korean population.
12743658 2003 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.
12719941 2003 Association study between interleukin-12 receptor beta1/beta2 genes and type 1 diabetes or asthma in the Japanese population.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11940489 2002 The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes.
11441083 2001 A role for IL-12 receptor expression and signal transduction in host defense in leprosy.
11438525 2001 Silencer activity of NFATc2 in the interleukin-12 receptor beta 2 proximal promoter in human T helper cells.
11306945 Reduced interferon-gamma production and mutations of the interleukin-12 receptor beta(2) chain gene in atopic subjects.
11114383 2000 Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
10663559 2000 Genomic organization of the human interleukin-12 receptor beta2-chain gene.
10600539 1999 Mutations of the IL-12 receptor beta2 chain gene in atopic subjects.
10415122 1999 Direct interaction of STAT4 with the IL-12 receptor.
10198225 1999 Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus.
9890938 1999 Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling.
9605872 1997 Assignment of IL12RB2 to human chromosome 1p31.3-->p31.2 between D1S230 and D1S198.
9498755 1998 Analysis of the multiple interactions between IL-12 and the high affinity IL-12 receptor complex.
9284929 1997 Assignment of IL12RB1 and IL12RB2, interleukin-12 receptor beta 1 and beta 2 chains, to human chromosome 19 band p13.1 and chromosome 1 band p31.2, respectively, by in situ hybridization.
9120388 1997 Selective expression of an interleukin-12 receptor component by human T helper 1 cells.
8943050 1996 A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits.
8401589 1993 The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.
7911493 1994 Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130.