IL2RG Gene (Interleukin-2 Receptor Subunit Gamma): Structure, Function, and Clinical Significance
A comprehensive biomedical resource on IL2RG, its role in immune signaling, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | IL2RG |
|---|---|
| Full Name | Interleukin 2 receptor subunit gamma |
| Gene Type | Protein coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 3561 ncbi.nlm.nih.gov/gene/3561 |
| Ensembl ID | ENSG00000147168 |
| UniProt ID | P31785 |
| OMIM ID | 308380 |
| HGNC ID | 6010 |
| Aliases | CD132, SCIDX1, IMD4, p64, IL-2RG |
Description
The IL2RG gene encodes the common gamma chain (γc), a critical subunit of multiple cytokine receptors including those for interleukins 2, 4, 7, 9, 15, and 21. This protein is essential for the development and function of lymphocytes, particularly T cells and natural killer (NK) cells. Mutations in IL2RG cause X-linked severe combined immunodeficiency (SCID-X1), a life-threatening condition characterized by absent T cells and NK cells, with B cells present but non-functional. The gene is located on the X chromosome, and its expression is primarily in immune tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked severe combined immunodeficiency (SCID-X1) | Loss-of-function mutations in IL2RG disrupt cytokine signaling, leading to impaired T and NK cell development. | ClinVar; OMIM #300400 |
| Immunodeficiency 4 (IMD4) | Mutations in IL2RG cause a form of combined immunodeficiency with variable severity. | OMIM #300400; HGNC |
| Severe combined immunodeficiency, autosomal recessive (rare) | Biallelic mutations in IL2RG (in females) can cause SCID, though X-linked inheritance is typical. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 10.8 | High |
| Bone marrow | 8.2 | Medium |
| Thymus | 7.9 | Medium |
| Blood | 6.5 | Medium |
| Lung | 2.1 | Low |
| Small intestine | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| MOLT-4 (T-ALL) | 12.7 | High expression |
| GM12878 (B-lymphocyte) | 9.4 | Medium expression |
| HeLa (cervical carcinoma) | 1.2 | Low expression |
| A549 (lung carcinoma) | 0.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.202G>A (p.Gly68Arg) | Missense | Rare | Loss of function; disrupts cytokine binding |
| c.654C>T (p.Arg218Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.868C>T (p.Arg290Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.IVS1+1G>A | Splice site | Rare | Loss of function; aberrant splicing |
| c.925A>G (p.Lys309Glu) | Missense | Rare | Loss of function; affects receptor dimerization |
Mutation functional classification
Loss of Function (LOF)
Most IL2RG mutations are loss-of-function, leading to SCID-X1. These include nonsense, frameshift, splice-site, and missense mutations that impair protein expression or signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for IL2RG in the context of disease.
Dominant Negative (DN)
Not applicable; IL2RG is X-linked and mutations are typically recessive in males (hemizygous) or cause disease in females due to skewed X-inactivation.
View complete mutation data：
Gene Ontology (GO)
| • Interleukin-2 receptor activity | • Interleukin-4 receptor activity |
| • Interleukin-7 receptor activity | • Interleukin-9 receptor activity |
| • Interleukin-15 receptor activity | • Interleukin-21 receptor activity |
| • Cytokine receptor activity | • Protein binding |
| • Signal transduction | • Immune response |
Pathways
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Jak-STAT signaling pathway (KEGG hsa04630)
• Hematopoietic cell lineage (KEGG hsa04640)
• T cell receptor signaling pathway (KEGG hsa04660)
• Natural killer cell mediated cytotoxicity (KEGG hsa04650)
Protein Summary
The IL2RG protein, also known as the common gamma chain (γc), is a type I transmembrane protein of 369 amino acids. It contains an extracellular domain with a WSXWS motif, a transmembrane region, and a cytoplasmic tail that interacts with Janus kinases (JAK1 and JAK3). The γc chain is a shared component of receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Upon ligand binding, it initiates intracellular signaling cascades, primarily the JAK-STAT pathway, which is crucial for lymphocyte proliferation, differentiation, and survival. Defects in this protein lead to severe immune dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL2RG Knockout HEK293 Cell Line | EDJ-KQ495 | Human | 3561 | Details Get a Quote |
| IL2RG Knockout HeLa Cell Line | EDJ-KQ53633 | Human | 3561 | Details Get a Quote |
| IL2RG Knockout A-549 Cell Line | EDJ-KQ62108 | Human | 3561 | Details Get a Quote |
| IL2RG Knockout HCT 116 Cell Line | EDJ-KQ70595 | Human | 3561 | Details Get a Quote |
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