IL17RB (Interleukin 17 Receptor B): A Key Mediator in Mucosal Immunity and Tumorigenesis
Explore the IL17RB gene, its protein product, associated diseases, expression patterns, and functional roles in health and disease.
Gene Information Card
| Symbol | IL17RB |
|---|---|
| Full Name | Interleukin 17 Receptor B |
| Gene Type | protein coding |
| Chromosomal Location | 3p28.1 |
| NCBI Gene ID | 55540 ncbi.nlm.nih.gov/gene/55540 |
| Ensembl ID | ENSG00000163736 |
| UniProt ID | Q9NRM6 |
| OMIM ID | 605458 |
| HGNC ID | 18015 |
| Aliases | IL17BR, CRL4, IL-17RB, IL17Rh1 |
Description
The IL17RB gene encodes the Interleukin 17 Receptor B (IL-17RB), a type I transmembrane protein that is a component of the interleukin-17 receptor family. This receptor is known to bind with high affinity to its ligands, Interleukin-17B (IL-17B) and Interleukin-25 (IL-25, also known as IL-17E). IL-17RB signaling plays a critical role in the regulation of mucosal immunity, particularly in the context of type 2 immune responses, by promoting the production of Th2 cytokines. Beyond its role in immunity, IL17RB has been implicated in the progression of various cancers, where its activation can promote tumor cell proliferation, survival, and metastasis. The receptor functions by forming a complex with other subunits, such as IL-17RA, to mediate downstream signaling cascades, including the activation of NF-kappa-B and MAPK pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Breast Cancer | IL-17B/IL-17RB signaling promotes tumor growth, metastasis, and resistance to therapy by activating downstream pathways like ERK1/2, NF-κB, and PI3K/AKT, which enhance cell proliferation and survival. | Overexpression of IL17RB is associated with poor prognosis in breast cancer patients. Functional studies show that knockdown of IL17RB reduces tumorigenicity in xenograft models. (PMID: 21804535) |
| Pancreatic Cancer | IL-17B/IL-17RB autocrine signaling drives tumor progression and metastasis by activating the NF-κB pathway and upregulating the expression of pro-metastatic genes. | High IL17RB expression is correlated with advanced tumor stage and poor survival in pancreatic cancer patients. In vitro and in vivo studies demonstrate that blocking IL-17RB signaling inhibits tumor growth and metastasis. (PMID: 26420884) |
| Asthma | IL-25 (IL-17E) signaling through IL-17RB on Th2 cells and innate lymphoid cells (ILC2s) amplifies type 2 inflammation, leading to airway hyperresponsiveness, eosinophilia, and mucus production. | Elevated levels of IL-25 and increased IL17RB expression are found in the airways of asthmatic patients. Mouse models of asthma show that IL-17RB deficiency attenuates airway inflammation. (PMID: 11201731) |
| Inflammatory Bowel Disease (IBD) | IL-25/IL-17RB signaling is involved in regulating mucosal immunity and maintaining intestinal barrier integrity. Dysregulation of this axis can contribute to chronic intestinal inflammation. | Studies in mouse models of colitis show that IL-25 administration can ameliorate inflammation, while IL-17RB knockout mice exhibit exacerbated disease, suggesting a protective role in some contexts. (PMID: 21300875) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Kidney | 18.2 | Medium |
| Testis | 12.5 | Low |
| Liver | 10.1 | Low |
| Lung | 8.4 | Low |
| Small Intestine | 7.9 | Low |
| Colon | 6.8 | Low |
| Breast | 5.2 | Low |
| Pancreas | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| MCF7 (Breast Cancer) | 15.3 | Moderate expression; associated with hormone-responsive breast cancer cell lines. |
| PANC-1 (Pancreatic Cancer) | 12.8 | Moderate expression; implicated in autocrine IL-17B signaling loop. |
| A549 (Lung Cancer) | 8.7 | Low to moderate expression. |
| HepG2 (Liver Cancer) | 6.5 | Low expression. |
| Jurkat (T-cell leukemia) | 2.1 | Very low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.602C>T (p.Pro201Leu) | Missense | Rare (<0.01%) | Located in the extracellular domain; predicted to affect ligand binding affinity, potentially altering signaling strength. |
| c.844G>A (p.Val282Ile) | Missense | Rare (<0.01%) | Located in the transmembrane domain; may affect receptor dimerization or membrane localization. |
| c.1123A>G (p.Thr375Ala) | Missense | Rare (<0.01%) | Located in the intracellular domain; potentially impacts interaction with downstream signaling molecules. |
| c.1265C>T (p.Ser422Phe) | Missense | Rare (<0.01%) | Located in the intracellular TIR-like domain; may disrupt signal transduction. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in IL17RB are not well-characterized in human disease but are predicted to impair ligand binding or signal transduction, leading to reduced type 2 immune responses. This could potentially increase susceptibility to certain infections or alter inflammatory responses.
Gain of Function (GOF)
Gain-of-function mutations, such as gene amplifications or activating point mutations, are more commonly implicated in cancer. These mutations can lead to constitutive or enhanced signaling, promoting tumor cell proliferation, survival, and metastasis.
Dominant Negative (DN)
Dominant-negative mutations are theoretically possible if a mutant IL17RB subunit can dimerize with the wild-type receptor but fails to signal, thereby reducing the overall functional receptor complex on the cell surface. Such mutations have not been definitively identified in clinical studies.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-17 receptor activity | • protein homodimerization activity |
| • protein heterodimerization activity | • signal transducer activity |
| • plasma membrane | • integral component of plasma membrane |
| • immune response | • inflammatory response |
| • cell surface receptor signaling pathway | • positive regulation of NF-kappaB transcription factor activity |
| • positive regulation of MAPK cascade | • positive regulation of cell proliferation |
| • positive regulation of cytokine production |
Pathways
• IL-17 signaling pathway
• Cytokine-cytokine receptor interaction
• NF-kappa B signaling pathway
• MAPK signaling pathway
• Th17 cell differentiation
• Asthma pathway
Protein Summary
The IL-17RB protein is a 502-amino acid type I transmembrane receptor. It consists of a large extracellular domain containing a fibronectin type III domain, which is responsible for ligand binding, a single transmembrane helix, and a long intracellular domain. The intracellular domain lacks intrinsic kinase activity but contains conserved motifs that allow it to recruit adaptor proteins like Act1 (TRAF3IP2) upon ligand stimulation. This interaction initiates downstream signaling cascades, primarily activating the NF-κB and MAPK pathways. IL-17RB can form homodimers or heterodimers with IL-17RA. While the IL-17RA/IL-17RB heterodimer is the primary receptor for IL-25 (IL-17E), the IL-17RB homodimer is the main receptor for IL-17B. The receptor is post-translationally modified by N-linked glycosylation, which is essential for its proper folding and cell surface expression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL17RB Knockout HEK293 Cell Line | EDJ-KQ2199 | Human | 55540 | Details Get a Quote |
| IL17RB Knockout HCT 116 Cell Line | EDJ-KQ21130 | Human | 55540 | Details Get a Quote |
| IL17RB Knockout A-549 Cell Line | EDJ-KQ22437 | Human | 55540 | Details Get a Quote |
| IL17RB Knockout HeLa Cell Line | EDJ-KQ22439 | Human | 55540 | Details Get a Quote |
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