Affinage

IL2RG

Cytokine receptor common subunit gamma · UniProt P31785

Length
369 aa
Mass
42.3 kDa
Annotated
2026-06-10
100 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL2RG encodes the common gamma chain (γc/CD132), a shared signal-transducing subunit used by the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, and its loss produces an early block in T and NK lymphocyte differentiation by depriving early lymphoid progenitors of growth, survival, and differentiation signals (PMID:10784449). Point mutations spanning all eight exons—splice-site disruptions, premature terminations, and amino acid substitutions—cause X-linked SCID (SCIDX1), the gene mapping to Xq13.1, with γc required to associate with the IL-2 receptor beta chain for ligand internalization and cell activation (PMID:8401490, PMID:9058718). Signaling proceeds through the γc intracellular domain, which recruits JAK3 to drive STAT5 phosphorylation; a critical three-residue region of this domain is required for receptor stabilization and JAK3-dependent signaling, and mutations such as R328X impair JAK3 binding while permitting partial JAK3-independent STAT5 phosphorylation (PMID:31799703). The lymphoid requirement is direct and cell-autonomous: retroviral restoration of γc in patient CD34+ cells rescues T and NK (and B) cell development and function (PMID:10784449, PMID:12070011), and a spontaneous reversion to normal sequence in committed T-cell progenitors conferred selective outgrowth, establishing γc as necessary for T-cell competitive fitness (PMID:23403317). Hypomorphic lesions act largely by limiting surface receptor: the p.Pro58Ser mutation traps γc at the ER/Golgi interface through aberrant interactions, impairing IL-2/IL-21-driven STAT5 phosphorylation and proliferation (PMID:32072341). A labile Cys183–Cys232 disulfide bond, reducible by thioredoxin, GILT, and protein disulfide isomerase, modulates IL-2-dependent proliferation and STAT5 signaling, linking receptor function to redox state during inflammation (PMID:22645657). Beyond lymphocytes, functional γc/JAK3/STAT5 signaling operates in fibroblast-like synoviocytes and contributes to the growth of pancreatic cancer cells and ITK-SYK-driven T-cell lymphoma cells (PMID:11238664, PMID:29137350, PMID:31545408).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Established the molecular cause of X-linked SCID by mapping IL2RG and showing its mutations ablate the IL-2 receptor gamma chain required for receptor assembly and activation.

    Evidence FISH/somatic-cell-hybrid mapping, genomic sequencing, and mutation analysis in SCID pedigrees

    PMID:8401490

    Open questions at the time
    • Did not resolve which downstream signaling molecule the gamma chain recruits
    • Sharing of the chain across multiple cytokine receptors not yet established
  2. 1997 High

    Defined the mutational landscape across the full gene and linked the intracellular domain to interaction with signal-transducing molecules including JAK3.

    Evidence Sequencing, SSCP, surface anti-γc staining, and X-inactivation analysis in a large SCID cohort

    PMID:9058718

    Open questions at the time
    • Genotype-to-residual-signaling correlations for individual mutations not functionally dissected
    • JAK3-binding region not mapped to specific residues
  3. 2000 High

    Demonstrated directly that IL2RG is the shared gamma chain whose restoration rescues lymphoid development, defining its role in delivering signals to early lymphoid progenitors.

    Evidence Retroviral IL2RG transfer into patient CD34+ cells with immune reconstitution and functional assays

    PMID:10784449

    Open questions at the time
    • Did not address insertional/oncogenic risks of the corrective vector
    • Relative contribution of each cytokine receptor to the rescue not parsed
  4. 2001 Medium

    Showed γc signaling is not lymphocyte-restricted by demonstrating functional IL-2Rβ/γc receptors on fibroblast-like synoviocytes driving chemokine production.

    Evidence Receptor detection, IL-2 stimulation, anti-CD122 blockade, and tyrosine phosphorylation/MCP-1 readouts in FLS

    PMID:11238664

    Open questions at the time
    • JAK/STAT involvement in FLS not directly tested
    • In vivo relevance to synovial pathology not established
  5. 2002 Medium

    Established that γc expression is specifically required for lymphoid lineage differentiation from progenitors in vivo.

    Evidence Retroviral correction of patient CD34+ cells in a chimeric sheep fetal transplantation model with lineage analysis

    PMID:12070011

    Open questions at the time
    • Single large-animal model, not human in vivo
    • Quantitative thresholds of γc needed per lineage not defined
  6. 2004 Low

    Indicated differential cytokine-receptor sensitivity to limiting γc, with IL-15-mediated NK signaling preferentially retained.

    Evidence Splice-variant RT-PCR and surface γc FACS in a single SCID patient with NK+ phenotype

    PMID:15108287

    Open questions at the time
    • Single patient, no functional signaling assays to confirm IL-15 retention
    • Mechanism of preferential retention not tested
  7. 2006 Medium

    Distinguished γc restoration from oncogenesis, showing IL2RG itself is not directly transforming but enables developmental progression permissive for LMO2-driven leukemogenesis.

    Evidence Comparative retroviral overexpression of IL2RG vs LMO2 in human CD34+ cells with T-cell development assays

    PMID:16988660

    Open questions at the time
    • Did not exclude rare insertional cooperative events with IL2RG vector
    • Single in vitro developmental system
  8. 2012 Medium

    Identified a redox-regulatory mechanism, the labile Cys183–Cys232 disulfide, whose reduction impairs IL-2 binding and STAT5 signaling.

    Evidence In vitro enzymatic reduction, proliferation and STAT5 phosphorylation assays, and an LPS in vivo inflammation model

    PMID:22645657

    Open questions at the time
    • Direct structural confirmation of altered IL-2 binding not obtained
    • Physiological contexts where reduction occurs incompletely defined
  9. 2013 Medium

    Provided isogenic in vivo evidence that γc expression confers T-cell competitive fitness via a spontaneous reversion event.

    Evidence Reversion sequencing, surface CD132 and subset flow cytometry, TCR repertoire analysis, longitudinal follow-up in a patient

    PMID:23403317

    Open questions at the time
    • Single patient natural experiment
    • Mechanism of selective CD8+ advantage not dissected
  10. 2017 Medium

    Extended γc/JAK3 signaling to cell-autonomous tumor growth in pancreatic cancer.

    Evidence CRISPR knockout of IL2RG in orthotopically implanted pancreatic cancer cells with tumor growth and JAK3 expression readouts

    PMID:29137350

    Open questions at the time
    • Single in vivo loss-of-function approach
    • Ligand/upstream cytokine driving the signaling not identified
  11. 2019 Medium

    Showed the IL2RG/JAK3/STAT5 axis is required for ITK-SYK-driven oncogenic growth, converging genetic and pharmacologic evidence.

    Evidence siRNA knockdown vs tofacitinib in ITK-SYK-expressing Jurkat cells with proliferation, apoptosis, and cell-cycle assays

    PMID:31545408

    Open questions at the time
    • Single cell-line model
    • In vivo relevance not tested
  12. 2020 Medium

    Defined two hypomorphic mechanisms: mislocalization of γc to the ER/Golgi (p.Pro58Ser) and impaired JAK3 binding with residual JAK3-independent STAT5 signaling (R328X), mapping a critical intracellular three-residue region.

    Evidence BioID proximity labeling, Co-IP with JAK3, surface expression, STAT5 phosphorylation, and proliferation assays on patient mutants

    PMID:31799703 PMID:32072341

    Open questions at the time
    • Identity of the JAK3-independent STAT5 kinase not established
    • ER/Golgi retention partners not validated reciprocally
  13. 2022 Low

    Implicated CD132 signaling in decidual macrophage-mediated maternal-fetal tolerance.

    Evidence Adoptive transfer of Tim-3+ vs Tim-3- macrophages, CD132 pathway blockade, and pregnancy-outcome readouts in mice

    PMID:35550500

    Open questions at the time
    • CD132 involvement inferred from pathway blockade, not gene-specific perturbation
    • Single lab, indirect mechanistic link

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the JAK3-independent kinase mediating residual STAT5 phosphorylation, and the structural basis by which the critical intracellular region stabilizes the receptor and recruits JAK3, remain unresolved.
  • No structure of the γc intracellular domain bound to JAK3 in the corpus
  • JAK3-independent STAT5 activation mechanism uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
IL2RBJAK3STAT5
Complex memberships
IL-2 receptor complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 IL2RG maps to Xq13.1 and encodes the gamma chain of the IL-2 receptor; point mutations in IL2RG (including splice-donor site ablation, premature chain termination, and amino acid changes) are causally associated with X-linked SCID, establishing IL2RG as the SCIDX1 gene. The gamma chain was shown to be required to associate with the beta chain for IL-2 internalization and cell activation. Fluorescence in situ hybridization, somatic cell hybrid PCR mapping, genomic sequencing, mRNA expression analysis in patient B-cell lines, mutation analysis in SCID pedigrees Human molecular genetics High 8401490
2000 IL2RG encodes the gamma-c cytokine receptor subunit shared by IL-2, IL-4, IL-7, IL-9, and IL-15 receptors; mutations cause an early block in T and NK lymphocyte differentiation by impairing delivery of growth, survival, and differentiation signals to early lymphoid progenitors. Retroviral transfer of IL2RG cDNA into CD34+ cells restored T and NK cell development and function in SCID-X1 patients. Retrovirus-mediated gene transfer into autologous CD34+ cells, patient follow-up with T/NK/B cell counts and functional assays including antigen-specific responses Science (New York, N.Y.) High 10784449
1997 Sixty-two different mutations spanning all eight IL2RG exons were found in 87 SCID cases; abnormal gamma-c chains are expressed in up to two-thirds of patients. Mutations disrupt conserved cytokine receptor family motifs or alter the intracellular domain critical for interaction with signal-transducing molecules including JAK3. DNA sequencing, SSCP, mRNA expression analysis, cell-surface staining with anti-gamma-c antibodies, X-chromosome inactivation analysis in 103 unrelated SCID males Blood High 9058718
2012 The Cys183–Cys232 disulfide bond in CD132 (IL2RG) is labile and can be reduced by thioredoxin, gamma-interferon-inducible lysosomal thiolreductase, and protein disulfide isomerase. Reduction of this disulfide bond inhibits IL-2-dependent T cell proliferation and STAT-5 signaling, and is proposed to impair IL-2 binding to the receptor complex. The bond is also reduced in vivo in an LPS-induced acute inflammation model. In vitro reduction assays with recombinant enzymes, T-cell proliferation assay, STAT-5 phosphorylation analysis, LPS-induced in vivo inflammation model, structural analysis of published receptor complex data Open biology Medium 22645657
2006 Retroviral overexpression of IL2RG in human CD34+ cells has no effect on T-cell development, whereas overexpression of LMO2 leads to severe abnormalities. IL2RG restoration of normal IL-7 receptor signaling in SCID precursor cells allows T-cell progression to stages permissive for pro-leukemic LMO2 effects, but IL2RG itself is not directly oncogenic. Retroviral overexpression of IL2RG or LMO2 in human CD34+ cells, in vitro T-cell development assay, comparison of developmental outcomes Nature Medium 16988660
2001 Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed on fibroblast-like synoviocytes (FLS). IL-2 stimulation of FLS via these receptors induces MCP-1 production and increased tyrosine phosphorylation, an effect partially blocked by anti-CD122 neutralizing antibody. Western blot and RT-PCR for CD122 and CD132 protein/mRNA, receptor quantification (binding sites), ELISA for MCP-1, anti-CD122 blocking antibody, tyrosine phosphorylation assay Journal of immunology (Baltimore, Md. : 1950) Medium 11238664
2002 Retroviral transduction of IL2RG into XSCID patient CD34+ cells restores cell-surface gamma-c expression and permits development of T and B cells (but not myeloid-only differentiation seen with untransduced cells) in the chimeric sheep fetal model, demonstrating that gamma-c expression is specifically required for lymphoid (T and B cell) differentiation from hematopoietic progenitors. Retroviral gene transfer, surface gamma-c expression analysis, chimeric sheep fetal transplantation model, lineage differentiation analysis Blood Medium 12070011
2017 CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth and reduced JAK3 expression in vivo, indicating that IL2RG/JAK3 signaling contributes to pancreatic cancer cell-autonomous growth. CRISPR/Cas9 knockout of IL2RG in pancreatic cancer cells, orthotopic implantation in mice, tumor growth measurement, JAK3 expression analysis in tumors Oncotarget Medium 29137350
2019 siRNA-specific knockdown of IL2RG in Jurkat cells expressing the ITK-SYK fusion gene showed the same suppression of cell growth, apoptosis induction, and G1/S cell cycle arrest as the JAK3-selective inhibitor tofacitinib, demonstrating that the IL2RG/JAK3/STAT5 signaling axis is required for ITK-SYK-driven oncogenic growth. siRNA knockdown of IL2RG, cell proliferation assay, apoptosis assay, cell cycle analysis, comparison with pharmacological JAK3 inhibition (tofacitinib) in Jurkat cells International journal of oncology Medium 31545408
2020 A hypomorphic IL2RG p.Pro58Ser mutation impairs surface expression of IL2RG on lymphocytes. BioID proximity labeling showed aberrant interactions between the mutated IL2RG and ER/Golgi proteins, causing mislocalization of the mutated protein to the ER/Golgi interface rather than the plasma membrane, leading to impaired STAT5 phosphorylation in response to IL-2 and IL-21 and reduced T-cell proliferation. Flow cytometry for surface IL2RG expression, BioID proximity labeling, STAT5 phosphorylation assay, T-cell proliferation assay, IL-2 target gene expression analysis Journal of clinical immunology Medium 32072341
2020 The IL2RG R328X nonsense mutation allows partial STAT-5 phosphorylation through a JAK3-independent pathway. Co-immunoprecipitation demonstrated that the R328X mutant protein has impaired JAK3 binding. A critical three-amino-acid region in the gamma-c intracellular domain was identified as necessary for receptor stabilization and JAK3-dependent signaling. Co-immunoprecipitation of mutant IL2RG with JAK3, STAT-5 phosphorylation assays, CD132 surface expression analysis, functional lymphocyte assays in patients Clinical and experimental immunology Medium 31799703
2013 An IL2RG reversion mutation to normal sequence occurred specifically in committed T-cell progenitors and conferred selective outgrowth advantage to CD8+ T cells. Only revertant cells showed normal CD132 surface expression and normal cytokine-dependent proliferative responses, demonstrating that gamma-c expression is required for T-cell competitive fitness in vivo. IL2RG mutation and reversion analysis by sequencing, flow cytometry for CD132 surface expression and T-cell subset analysis, TCR repertoire analysis, longitudinal follow-up Haematologica Medium 23403317
2004 A novel splice-site mutation (c.468+3A>C in intron 3 of IL2RG) produces two aberrantly spliced gamma-c mRNA species with reduction of correctly spliced message to trace levels, resulting in failure to detect gamma-c on the surface of B and NK cells. The NK+ (but not T+) phenotype supports the hypothesis that IL-15 receptor-mediated signaling is preferentially retained as cell-surface gamma-c becomes limiting. Sequencing, RT-PCR for splice variant analysis, FACS for surface gamma-c expression on lymphocyte subsets Human mutation Low 15108287
2022 Tim-3+ decidual macrophages with higher CD132 expression induced Th2 and Treg bias in decidual CD4+ T cells; blockade of the CD132 pathway led to dysfunction of maternal-fetal tolerance and increased fetal loss, demonstrating a functional role for CD132 signaling in decidual macrophage-mediated immune regulation during pregnancy. Flow cytometry, adoptive transfer of Tim-3+ vs. Tim-3- macrophages into macrophage-depleted mice, CD132 pathway blockade with functional pregnancy outcome readout, microarray analysis Cell death & disease Low 35550500

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science (New York, N.Y.) 2787 14564000
2000 Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science (New York, N.Y.) 1883 10784449
2008 Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. The Journal of clinical investigation 1462 18688285
2008 Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. The Journal of clinical investigation 1016 18688286
1993 The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Human molecular genetics 229 8401490
2007 Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. The Journal of clinical investigation 210 17671652
2019 Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. The New England journal of medicine 188 30995372
2017 Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Science translational medicine 182 29021165
2007 Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo. The Journal of clinical investigation 166 17671654
2019 Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nature communications 157 30967552
1997 Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood 134 9058718
2012 Il2rg gene-targeted severe combined immunodeficiency pigs. Cell stem cell 125 22704516
2009 Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfection. Blood 117 19286997
2010 Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial. Blood 106 20228274
2006 Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. The Journal of infectious diseases 99 16425129
2010 A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells. Blood 91 20457870
2005 Failure of SCID-X1 gene therapy in older patients. Blood 83 15687233
2004 Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. Genetics in medicine : official journal of the American College of Medical Genetics 81 14726805
2013 Natural killer cells generated from cord blood hematopoietic progenitor cells efficiently target bone marrow-residing human leukemia cells in NOD/SCID/IL2Rg(null) mice. PloS one 76 23755121
2012 Multiorgan metastasis of human HER-2+ breast cancer in Rag2-/-;Il2rg-/- mice and treatment with PI3K inhibitor. PloS one 75 22737248
2009 Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy. PLoS genetics 63 19461887
2012 Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice. PloS one 59 23155466
2004 Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial. Blood 58 15585650
2017 Umbilical cord blood CD34+ progenitor-derived NK cells efficiently kill ovarian cancer spheroids and intraperitoneal tumors in NOD/SCID/IL2Rgnull mice. Oncoimmunology 57 28919991
2017 Decitabine enhances targeting of AML cells by CD34+ progenitor-derived NK cells in NOD/SCID/IL2Rgnull mice. Blood 56 29138222
2015 Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs. Cell stem cell 56 25772073
2006 Gene therapy: is IL2RG oncogenic in T-cell development? Nature 52 16988660
2015 Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1. Blood 50 25869287
2017 Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report. Blood 49 28209722
2022 Enhanced development of functional human NK cells in NOD-scid-IL2rgnull mice expressing human IL15. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 47 35959876
2016 Biallelic modification of IL2RG leads to severe combined immunodeficiency in pigs. Reproductive biology and endocrinology : RB&E 47 27809915
2012 Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg-/- mice. Clinical cancer research : an official journal of the American Association for Cancer Research 47 22383738
2014 NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer. Digestive diseases and sciences 46 24798995
2015 siRNA silencing of PD-1 ligands on dendritic cell vaccines boosts the expansion of minor histocompatibility antigen-specific CD8(+) T cells in NOD/SCID/IL2Rg(null) mice. Cancer immunology, immunotherapy : CII 44 25724840
2010 Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression. Molecular therapy : the journal of the American Society of Gene Therapy 44 20354504
2010 Molecular diagnosis of severe combined immunodeficiency--identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children. Journal of clinical immunology 42 21184155
2012 Transduction of human CD34+ repopulating cells with a self-inactivating lentiviral vector for SCID-X1 produced at clinical scale by a stable cell line. Human gene therapy methods 40 23075105
2005 Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1) by gene therapy in Australia. The Medical journal of Australia 37 15865589
2013 A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells. Haematologica 36 23403317
2019 IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 35 30622570
2019 Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency. Blood advances 35 30755435
2018 B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood 34 29728406
2014 Intravenous injection of a foamy virus vector to correct canine SCID-X1. Blood 34 24642749
2020 Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in ART-/-IL2RG-/ SCID Pigs. Frontiers in immunology 32 32117254
2011 Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning. Molecular therapy : the journal of the American Society of Gene Therapy 32 21750532
2012 Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor. Open biology 31 22645657
2015 IL2RG reversion event in a common lymphoid progenitor leads to delayed diagnosis and milder phenotype. Journal of clinical immunology 30 26076747
2001 Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production. Journal of immunology (Baltimore, Md. : 1950) 29 11238664
2000 Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency. Clinical immunology (Orlando, Fla.) 28 10794430
2020 IL2RG-deficient minipigs generated via CRISPR/Cas9 technology support the growth of human melanoma-derived tumours. Cell proliferation 27 32871045
2018 Generation of Immunodeficient Rats With Rag1 and Il2rg Gene Deletions and Human Tissue Grafting Models. Transplantation 25 29688994
2022 Tim-3+ decidual Mφs induced Th2 and Treg bias in decidual CD4+T cells and promoted pregnancy maintenance via CD132. Cell death & disease 23 35550500
2018 Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy. Blood advances 23 29720491
2020 The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. PloS one 22 33027304
2012 Multiple reversions of an IL2RG mutation restore T cell function in an X-linked severe combined immunodeficiency patient. Journal of clinical immunology 22 22460439
2009 A novel model of SCID-X1 reconstitution reveals predisposition to retrovirus-induced lymphoma but no evidence of gammaC gene oncogenicity. Molecular therapy : the journal of the American Society of Gene Therapy 22 19337236
2004 A novel splice-site mutation in the common gamma chain (gammac) gene IL2RG results in X-linked severe combined immunodeficiency with an atypical NK+ phenotype. Human mutation 22 15108287
1993 Refinement of linkage of human severe combined immunodeficiency (SCIDX1) to polymorphic markers in Xq13. American journal of human genetics 22 8317482
2019 Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nature communications 21 31796738
2015 Late-Onset Combined Immunodeficiency with a Novel IL2RG Mutation and Probable Revertant Somatic Mosaicism. Journal of clinical immunology 21 26407811
2017 IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth. Oncotarget 20 29137350
1998 The circulating common gamma chain (CD132) in inflammatory bowel disease. The American journal of gastroenterology 20 9517632
2019 Epstein-Barr Virus-Associated γδ T-Cell Lymphoproliferative Disorder Associated With Hypomorphic IL2RG Mutation. Frontiers in pediatrics 19 30778380
2020 Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency. Journal of clinical immunology 18 32072341
2001 Abundant expression of common cytokine receptor gamma chain (CD132) in rheumatoid joints. The Journal of rheumatology 18 11246656
2021 CD34+ progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rgnull mice. Oncoimmunology 17 34616589
2021 Somatic Reversion of a Novel IL2RG Mutation Resulting in Atypical X-Linked Combined Immunodeficiency. Genes 16 35052377
2019 Biological Characteristics of Severe Combined Immunodeficient Mice Produced by CRISPR/Cas9-Mediated Rag2 and IL2rg Mutation. Frontiers in genetics 16 31134127
2019 Comparison of biological features between severely immuno-deficient NOD/Shi-scid Il2rgnull and NOD/LtSz-scid Il2rgnull mice. Experimental animals 15 31118345
2016 A novel deletion mutation in IL2RG gene results in X-linked severe combined immunodeficiency with an atypical phenotype. Immunogenetics 15 27566612
2014 Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus. Scientific reports 15 24853770
2012 Description of a new xenograft model of metastatic neuroblastoma using NOD/SCID/Il2rg null (NSG) mice. In vivo (Athens, Greece) 15 22210712
2020 Generation and characterization of an Il2rg knockout Syrian hamster model for XSCID and HAdV-C6 infection in immunocompromised patients. Disease models & mechanisms 14 32651192
2020 Reference Values for Hematology, Plasma Biochemistry, Bone Marrow Cytology and Bone Histology of NOD.Cg-Prkdc SzJ Immunodeficient Mice. Journal of the American Association for Laboratory Animal Science : JAALAS 14 33046180
2019 A synonymous splice site mutation in IL2RG gene causes late-onset combined immunodeficiency. International journal of hematology 14 30850927
2023 Chlamydia muridarum infection causes bronchointerstitial pneumonia in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Veterinary pathology 13 37434451
2019 Ex Vivo Gene Therapy: Graft-versus-host Disease (GVHD) in NSG™ (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) Mice Transplanted with CD34+ Human Hematopoietic Stem Cells. Toxicologic pathology 12 31064282
2018 Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice. Molecular therapy : the journal of the American Society of Gene Therapy 12 29606506
2002 Retroviral transduction of IL2RG into CD34(+) cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras. Blood 12 12070011
2020 In Vivo Gene Therapy for Canine SCID-X1 Using Cocal-Pseudotyped Lentiviral Vector. Human gene therapy 11 32741228
2019 Genome profiling revealed the activation of IL2RG/JAK3/STAT5 in peripheral T‑cell lymphoma expressing the ITK‑SYK fusion gene. International journal of oncology 11 31545408
2017 CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/IL2rg-/- Mice Results in Severe Immunodeficiency. Scientific reports 11 28798321
2014 Higher susceptibility of NOD/LtSz-scid Il2rg (-/-) NSG mice to xenotransplanted lung cancer cell lines. Cancer management and research 11 25364273
2008 Establishing EGFP congenic mice in a NOD/Shi-scid IL2Rg(null) (NOG) genetic background using a marker-assisted selection protocol (MASP). Experimental animals 11 18946184
2019 Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells. Nature communications 10 31028274
2011 Correction of SCID-X1 using an enhancerless Vav promoter. Human gene therapy 10 20887212
2006 A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency. Journal of human genetics 10 16601912
2023 The SELP, CD93, IL2RG, and VAV1 Genes Associated with Atherosclerosis May Be Potential Diagnostic Biomarkers for Psoriasis. Journal of inflammation research 9 36876153
2023 Integrome signatures of lentiviral gene therapy for SCID-X1 patients. Science advances 9 37801507
2020 The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype. Clinical and experimental immunology 9 31799703
2012 Increased percentage of T cells with the expression of CD127 and CD132 in hypertrophic adenoid in children with otitis media with effusion. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 9 22382400
2012 A germline-competent embryonic stem cell line from NOD.Cg-Prkdc ( scid ) Il2rg ( tm1Wjl )/SzJ (NSG) mice. Transgenic research 9 22767020
1998 Mutation analysis by a non-radioactive single-strand conformation polymorphism assay in nine families with X-linked severe combined immunodeficiency (SCIDX1). British journal of haematology 9 9633906
1989 Linkage of PGK1 to X-linked severe combined immunodeficiency (IMD4) allows predictive testing in families with no surviving male. Human genetics 9 2606471
2022 Defects in mucosal immunity and nasopharyngeal dysbiosis in HSC-transplanted SCID patients with IL2RG/JAK3 deficiency. Blood 8 35157765
2018 Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg-/- mice. Protein & cell 8 29948854
2015 A New IL-2RG Gene Mutation in an X-linked SCID Identified through TREC/KREC Screening: a Case Report. Iranian journal of allergy, asthma, and immunology 8 26547715
2022 Allogeneic and xenogeneic lymphoid reconstitution in a RAG2 -/- IL2RG severe combined immunodeficient pig: A preclinical model for intrauterine hematopoietic transplantation. Frontiers in veterinary science 7 36311661
2021 Reduction of Graft-versus-Host-Disease in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) Mice by Cotransplantation of Syngeneic Human Umbilical Cord-Derived Mesenchymal Stromal Cells. Transplantation and cellular therapy 7 33964513
2015 CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice. Journal of comparative pathology 7 25670669

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