IL7R Gene (Interleukin 7 Receptor): Function, Mutations, and Associated Diseases
Comprehensive guide to IL7R: genomic location, protein function, expression, disease links, and mutation classification.
Gene Information Card
| Symbol | IL7R |
|---|---|
| Full Name | Interleukin 7 receptor |
| Gene Type | protein coding |
| Chromosomal Location | 5p13.2 |
| NCBI Gene ID | 3575 ncbi.nlm.nih.gov/gene/3575 |
| Ensembl ID | ENSG00000168685 |
| UniProt ID | P16871 |
| OMIM ID | 146661 |
| HGNC ID | 6024 |
| Aliases | CD127, IL7RA, IL-7R-alpha |
Description
The IL7R gene encodes the alpha subunit of the interleukin-7 receptor (IL-7Rα), a critical component for the development and homeostasis of lymphocytes, particularly T cells. The receptor is composed of the IL7Rα chain (encoded by this gene) and the common gamma chain (γc, encoded by IL2RG). IL-7 signaling is essential for V(D)J recombination of T-cell receptor genes, survival of naive and memory T cells, and regulation of immune responses. Mutations in IL7R can lead to severe combined immunodeficiency (SCID) or contribute to oncogenic transformation in certain leukemias and lymphomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Severe combined immunodeficiency (SCID) | Loss-of-function mutations in IL7R impair IL-7 signaling, leading to defective T-cell development and function. | ClinVar; OMIM #146661; PubMed studies |
| T-cell acute lymphoblastic leukemia (T-ALL) | Gain-of-function mutations (e.g., IL7R exon 6 insertions) cause constitutive activation of the receptor, promoting uncontrolled T-cell proliferation. | COSMIC; multiple studies (e.g., Zenatti et al., 2011) |
| Multiple sclerosis (MS) | Genetic variants (e.g., rs6897932) in IL7R are associated with altered splicing and increased soluble IL-7R levels, influencing immune dysregulation. | GWAS; ClinVar; PubMed |
| Rheumatoid arthritis | IL7R polymorphisms have been linked to increased susceptibility, possibly via enhanced IL-7 signaling in autoreactive T cells. | ClinVar; PubMed |
| Inflammatory bowel disease (IBD) | IL7R variants may affect mucosal T-cell homeostasis, contributing to chronic inflammation. | ClinVar; PubMed |
| Hodgkin lymphoma | Somatic mutations in IL7R have been observed, potentially driving aberrant signaling in malignant cells. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymphoid tissues (spleen, lymph node, tonsil) | High (e.g., spleen nTPM ~ 20-30) | High expression in T and B cells |
| Bone marrow | Moderate (nTPM ~ 10-20) | Expression in hematopoietic progenitors |
| Thymus | High (nTPM ~ 30-40) | Critical for T-cell development |
| Peripheral blood | Moderate (nTPM ~ 15-25) | Expressed on T cells, NK cells, monocytes |
| Lung | Low (nTPM < 5) | Limited expression in tissue-resident immune cells |
| Liver | Low (nTPM < 3) | Minimal expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | High (nTPM ~ 50) | Constitutive expression; used in IL-7 signaling studies |
| MOLT-4 (T-ALL) | High (nTPM ~ 40) | Overexpression due to mutations |
| K-562 (CML) | Low (nTPM ~ 5) | Minimal expression |
| HeLa (cervical carcinoma) | Low (nTPM ~ 2) | Non-immune cell line |
| A549 (lung carcinoma) | Low (nTPM ~ 1) | Non-immune cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.456+1G>A (splice site) | Splice-site mutation | Rare (found in SCID patients) | Loss of function: disrupts splicing, leading to truncated protein |
| c.839C>T (p.Thr280Met) | Missense | Rare (SCID) | Loss of function: impairs receptor trafficking or ligand binding |
| c.1024_1026dup (p.Leu342dup) | In-frame insertion | Somatic in T-ALL (5-10% of cases) | Gain of function: constitutive activation via disulfide bond formation |
| c.1025_1030del (p.Leu342_Leu343del) | In-frame deletion | Somatic in T-ALL | Gain of function: similar to insertion, constitutive signaling |
| rs6897932 (c.565A>G, p.Ile188Val) | SNP | Common (allele frequency ~25%) | Alters splicing, increases soluble IL-7R; associated with MS risk |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair IL-7Rα expression, ligand binding, or downstream signaling (e.g., JAK/STAT pathway) lead to SCID. These are typically recessive and result in T-cell deficiency.
Gain of Function (GOF)
Somatic mutations, particularly in exon 6, introduce cysteine residues that cause ligand-independent receptor dimerization and constitutive activation of JAK/STAT and PI3K/AKT pathways, driving T-ALL.
Dominant Negative (DN)
Some missense mutations may produce a truncated receptor that can dimerize with wild-type subunits, interfering with normal signaling, though this is less documented for IL7R.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-7 receptor activity | • cytokine receptor activity |
| • protein homodimerization activity | • protein heterodimerization activity |
| • signal transduction | • immune response |
| • T cell differentiation | • lymphocyte homeostasis |
| • JAK-STAT cascade | • positive regulation of cell proliferation |
Pathways
• IL-7 signaling pathway
• JAK-STAT signaling pathway
• PI3K-Akt signaling pathway
• T cell receptor signaling pathway
• Cytokine-cytokine receptor interaction
• Hematopoietic cell lineage
Protein Summary
The IL-7 receptor alpha chain (IL-7Rα) is a type I transmembrane glycoprotein of approximately 459 amino acids. It consists of an extracellular domain with a fibronectin type III domain, a transmembrane region, and a cytoplasmic tail containing Box1 and Box2 motifs essential for JAK1 binding. Upon IL-7 binding, IL-7Rα heterodimerizes with the common gamma chain (γc), activating JAK1 and JAK3, which phosphorylate STAT5, leading to transcriptional regulation of target genes like BCL2 and MYC. The receptor is critical for T-cell development, survival, and memory formation. Soluble IL-7Rα (sCD127) is generated by alternative splicing and can modulate IL-7 bioavailability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL7R Knockout HEK293 Cell Line | EDJ-KQ502 | Human | 3575 | Details Get a Quote |
| IL7R Knockout HeLa Cell Line | EDC10330 | Human | 3575 | Details Get a Quote |
| IL7R Knockout A-549 Cell Line | EDJ-KQ62114 | Human | 3575 | Details Get a Quote |
| IL7R Knockout HCT 116 Cell Line | EDJ-KQ70603 | Human | 3575 | Details Get a Quote |
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