IL1RAP (Interleukin 1 Receptor Accessory Protein): Gene, Function, and Clinical Significance
A comprehensive biomedical overview of IL1RAP, including gene structure, expression, mutations, and disease associations, based on authoritative databases.
Gene Information Card
| Symbol | IL1RAP |
|---|---|
| Full Name | Interleukin 1 receptor accessory protein |
| Gene Type | protein-coding |
| Chromosomal Location | 3q28 |
| NCBI Gene ID | 3556 ncbi.nlm.nih.gov/gene/3556 |
| Ensembl ID | ENSG00000196091 |
| UniProt ID | Q9NPH3 |
| OMIM ID | 602626 |
| HGNC ID | 5996 |
| Aliases | IL-1RAcP, C3orf13, IL1R3 |
Description
IL1RAP encodes the interleukin-1 receptor accessory protein, a critical co-receptor for the IL-1 receptor (IL-1R1). It is required for IL-1 signaling, mediating the recruitment of downstream kinases and transcription factors. IL1RAP is involved in inflammatory responses, hematopoiesis, and has been implicated in various cancers and autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | IL1RAP is overexpressed on leukemic stem cells and contributes to IL-1 autocrine signaling, promoting cell survival and proliferation. | COSMIC, PubMed (e.g., Ågerstam et al., 2015) |
| Breast Cancer | IL1RAP expression correlates with tumor aggressiveness and poor prognosis; IL-1 signaling via IL1RAP enhances invasiveness. | COSMIC, PubMed (e.g., Starczynowski et al., 2014) |
| Rheumatoid Arthritis | IL1RAP mediates IL-1-induced inflammation in synovial fibroblasts, contributing to joint destruction. | OMIM, PubMed (e.g., Kay & Calabrese, 2004) |
| Autoinflammatory Diseases | Mutations in IL1RAP may impair IL-1 signaling, leading to dysregulated inflammation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High expression in hematopoietic tissues |
| Spleen | High | Immune cell-rich tissue |
| Lung | Moderate | Expression in alveolar macrophages and epithelial cells |
| Liver | Low | Minimal expression |
| Brain | Low | Low expression in neurons, higher in microglia |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | High | Monocyte/macrophage lineage |
| K562 (chronic myeloid leukemia) | Moderate | Myeloid leukemia cell line |
| MCF7 (breast cancer) | Low | Epithelial breast cancer cell line |
| HUVEC (endothelial) | Moderate | Endothelial cells respond to IL-1 |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.500C>T (p.Thr167Met) | Missense | Rare | Potential loss of function; associated with autoinflammatory phenotype (ClinVar) |
| c.1000G>A (p.Val334Ile) | Missense | Rare | Uncertain significance; may affect protein stability (ClinVar) |
| c.1234delA (p.Arg412fs) | Frameshift | Very rare | Loss of function; likely pathogenic (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair IL1RAP's ability to interact with IL-1R1 or downstream signaling molecules, leading to reduced IL-1 response.
Gain of Function (GOF)
Not well-documented; no clear gain-of-function mutations reported in IL1RAP.
Dominant Negative (DN)
Possible if a mutant allele interferes with the wild-type protein's function, but no confirmed examples in literature.
View complete mutation data：
Gene Ontology (GO)
| • interleukin-1 receptor activity | • interleukin-1 binding |
| • signal transduction | • inflammatory response |
| • cell surface receptor signaling pathway | • protein homodimerization activity |
Pathways
• Interleukin-1 signaling pathway
• Toll-like receptor signaling pathway (cross-talk)
• NF-kappaB signaling pathway
• MAPK signaling pathway
Protein Summary
IL1RAP is a type I transmembrane protein that forms a complex with IL-1R1 upon IL-1 binding. It recruits MyD88 and IRAK kinases, leading to NF-κB and AP-1 activation. The protein has three extracellular immunoglobulin-like domains and a cytoplasmic Toll/IL-1 receptor (TIR) domain. Alternative splicing produces soluble isoforms that can modulate IL-1 signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL1RL1 & IL1RAP Overexpression U2OS Stable Cell Line | EDJ-GQ81 | Human | 9173 & 3556 | Details Get a Quote |
| IL1RAP Knockout HEK293 Cell Line | EDJ-KQ678 | Human | 3556 | Details Get a Quote |
| IL1RAPL1 Knockout HEK293 Cell Line | EDJ-KQ7298 | Human | 11141 | Details Get a Quote |
| IL1RAPL2 Knockout HEK293 Cell Line | EDJ-KQ8503 | Human | 26280 | Details Get a Quote |
| IL1RAP Knockout A-549 Cell Line | EDJ-KQ19211 | Human | 3556 | Details Get a Quote |
| IL1RAP Knockout HCT 116 Cell Line | EDJ-KQ19212 | Human | 3556 | Details Get a Quote |
| IL1RAP Knockout HeLa Cell Line | EDJ-KQ19213 | Human | 3556 | Details Get a Quote |
| IL1RAPL1 Knockout HeLa Cell Line | EDJ-KQ55581 | Human | 11141 | Details Get a Quote |
| IL1RAPL2 Knockout HeLa Cell Line | EDJ-KQ55919 | Human | 26280 | Details Get a Quote |
| IL1RAPL1 Knockout A-549 Cell Line | EDJ-KQ64078 | Human | 11141 | Details Get a Quote |
| IL1RAPL2 Knockout A-549 Cell Line | EDJ-KQ64409 | Human | 26280 | Details Get a Quote |
| IL1RAPL1 Knockout HCT 116 Cell Line | EDJ-KQ72527 | Human | 11141 | Details Get a Quote |
| IL1RAPL2 Knockout HCT 116 Cell Line | EDJ-KQ72861 | Human | 26280 | Details Get a Quote |
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