Details for: IL18R1

Gene ID: 8809

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IL18R1

Ensembl ID: ENSG00000115604

Description: interleukin 18 receptor 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • basophil CL0000767
    CSI 16.14
    rCSI 34.14%
    PRS 97.12
  • CD4-positive helper T cell CL0000492
    CSI 13.41
    rCSI 10.14%
    PRS 98.84
  • group 3 innate lymphoid cell CL0001071
    CSI 13
    rCSI 9.77%
    PRS 96.36
  • cerebral cortex endothelial cell CL1001602
    CSI 12.31
    rCSI 21.29%
    PRS 91.36
  • glutamatergic neuron CL0000679
    CSI 9.6
    rCSI 19.73%
    PRS 85.47
  • glial cell CL0000125
    CSI 7.35
    rCSI 27.98%
    PRS 89.62
  • neutrophil CL0000775
    CSI 6.53
    rCSI 36.53%
    PRS 92.01
  • mast cell CL0000097
    CSI 6.4
    rCSI 13.82%
    PRS 91.63
  • granulocyte CL0000094
    CSI 6.03
    rCSI 9.21%
    PRS 97.08
  • GABAergic neuron CL0000617
    CSI 5.23
    rCSI 17.51%
    PRS 84.4
  • alpha-beta T cell CL0000789
    CSI 4.7
    rCSI 5.51%
    PRS 98.44
  • intermediate monocyte CL0002393
    CSI 4.37
    rCSI 6.59%
    PRS 97.39
  • Langerhans cell CL0000453
    CSI 4.28
    rCSI 6.53%
    PRS 98.03
  • mature T cell CL0002419
    CSI 3.61
    rCSI 2.81%
    PRS 98.56
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.59
    rCSI 6.85%
    PRS 97.48
  • hepatic stellate cell CL0000632
    CSI 3.55
    rCSI 13.29%
    PRS 92.13
  • renal interstitial pericyte CL1001318
    CSI 3.23
    rCSI 8.89%
    PRS 93.36
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 3.21
    rCSI 2.41%
    PRS 98.4
  • blood vessel endothelial cell CL0000071
    CSI 3.15
    rCSI 6.53%
    PRS 93.48
  • pulmonary artery endothelial cell CL1001568
    CSI 3.08
    rCSI 4.19%
    PRS 97.21
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.85
    rCSI 2.58%
    PRS 93.79
  • T-helper 17 cell CL0000899
    CSI 2.64
    rCSI 2.1%
    PRS 99.03
  • T follicular helper cell CL0002038
    CSI 2.56
    rCSI 1.91%
    PRS 98.64
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 2.43
    rCSI 6.98%
    PRS 99.19
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 2.38
    rCSI 27.64%
    PRS 98.11
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.27
    rCSI 2.74%
    PRS 97.47
  • cardiac endothelial cell CL0010008
    CSI 2.23
    rCSI 9%
    PRS 95.17
  • T-helper 1 cell CL0000545
    CSI 1.83
    rCSI 3.3%
    PRS 98.45
  • myeloid dendritic cell CL0000782
    CSI 1.81
    rCSI 2.63%
    PRS 98.78
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 1.75
    rCSI 5.39%
    PRS 95.45
  • helper T cell CL0000912
    CSI 1.63
    rCSI 2.3%
    PRS 89.87
  • innate lymphoid cell CL0001065
    CSI 1.61
    rCSI 3.32%
    PRS 88.86
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 1.6
    rCSI 4.14%
    PRS 98.4
  • lung macrophage CL1001603
    CSI 1.03
    rCSI 2.3%
    PRS 97.67
  • group 2 innate lymphoid cell CL0001069
    CSI 0.59
    rCSI 3.18%
    PRS 98.48

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [IL18R1](/details-gene/8809) (Interleukin 18 Receptor 1) is a protein-coding gene located on chromosome 2q12.1. It encodes the alpha chain of the interleukin-18 (IL-18) receptor, a member of the interleukin-1 receptor superfamily [Link](https://pubmed.ncbi.nlm.nih.gov/8626725/). This receptor is a critical component for mediating the biological effects of IL-18, a pro-inflammatory cytokine that plays a pivotal role in driving T-helper 1 (Th1) cell responses, natural killer cell activation, and interferon-gamma (IFN-γ) production [Link](https://pubmed.ncbi.nlm.nih.gov/10653850/). **Overall**, expression data reveals that [IL18R1](/details-gene/8809) is a highly significant gene in various immune cells, particularly [basophils](/details-cell/CL0000767), [CD4-positive helper T cells](/details-cell/CL0000492), and [group 3 innate lymphoid cells](/details-cell/CL0001071), underscoring its central function in both innate and adaptive immunity. Notably, its significant expression in non-immune cells, including [cerebral cortex endothelial cells](/details-cell/CL1001602) and [glutamatergic neurons](/details-cell/CL0000679), suggests broader physiological roles, potentially in neuroinflammation and vascular biology. ## Cellular Roles and Expression Landscape The expression profile of [IL18R1](/details-gene/8809) highlights its profound importance in the immune system. The gene demonstrates its highest significance (CSI: 16.14) in [basophils](/details-cell/CL0000767), a key cell type involved in allergic inflammation and immune regulation. This is closely followed by high significance in cell types central to adaptive and innate immunity, including [CD4-positive helper T cells](/details-cell/CL0000492) (CSI: 13.41), [group 3 innate lymphoid cells](/details-cell/CL0001071) (CSI: 13.00), [neutrophils](/details-cell/CL0000775) (CSI: 6.53), and [mast cells](/details-cell/CL0000097) (CSI: 6.40). This pattern is consistent with the established role of IL-18 signaling in promoting Th1 differentiation and activating effector functions in these lineages. Intriguingly, the data also reveal a significant expression signature for [IL18R1](/details-gene/8809) outside of the hematopoietic system. Its high Cell Significance Index in [cerebral cortex endothelial cells](/details-cell/CL1001602) (CSI: 12.31) and notable presence in neuronal populations such as [glutamatergic neurons](/details-cell/CL0000679) (CSI: 9.60) and [GABAergic neurons](/details-cell/CL0000617) (CSI: 5.23) suggests a direct role for IL-18 signaling within the central nervous system. This may involve modulation of blood-brain barrier function, regulation of neuronal activity, or participation in neuroinflammatory processes. The expression in [pulmonary capillary endothelial cells](/details-cell/CL4028001) further supports a role in vascular biology beyond the CNS. ## Pathways and Molecular Function Functionally, [IL18R1](/details-gene/8809) is integral to cytokine-mediated signaling pathways that govern immune responses. As a cell surface protein located on the [plasma membrane](/details-cell/GO:0005886), it functions as the ligand-binding component of the [interleukin-18 receptor complex](/details-cell/GO:0045092) [Link](https://pubmed.ncbi.nlm.nih.gov/11046021/). Its primary molecular functions are [interleukin-18 binding](/details-cell/GO:0042007) and [interleukin-18 receptor activity](/details-cell/GO:0042008). Upon binding IL-18, the receptor complex initiates the [interleukin-18-mediated signaling pathway](/details-cell/GO:0035655), which is a key process within the broader frameworks of [cytokine signaling in the immune system](/details-pathway/R-HSA-1280215) and specifically [interleukin-1 family signaling](/details-pathway/R-HSA-446652). This signaling cascade leads to the [positive regulation of nf-kappab transcription factor activity](/details-cell/GO:0051092), a central hub for inflammatory gene expression. The downstream biological consequences are highly relevant to the cell types where [IL18R1](/details-gene/8809) is prominently expressed. These include [T-helper 1 cell differentiation](/details-cell/GO:0045063), [natural killer cell activation](/details-cell/GO:0030101), and the [positive regulation of type ii interferon production](/details-cell/GO:0032729) (i.e., IFN-γ), which collectively orchestrate a robust inflammatory and cell-mediated immune response [Link](https://pubmed.ncbi.nlm.nih.gov/10925275/). ## Research Directions The expression profile and functional annotation of [IL18R1](/details-gene/8809) suggest several avenues for future investigation, particularly concerning its role beyond canonical immunology. **Proposed Hypotheses:** 1. Given its high significance in [cerebral cortex endothelial cells](/details-cell/CL1001602) and [glutamatergic neurons](/details-cell/CL0000679), [IL18R1](/details-gene/8809)-mediated signaling may directly regulate blood-brain barrier permeability and neuronal excitability during neuroinflammatory events, contributing to the pathogenesis of conditions like ischemic stroke or multiple sclerosis. 2. The exceptionally high CSI of [IL18R1](/details-gene/8809) in [basophils](/details-cell/CL0000767) suggests that IL-18 acts as a primary, non-IgE-mediated activator of these cells, potentially driving steroid-resistant allergic inflammation or contributing to host defense against certain pathogens. **Experimental Approach:** To test the first hypothesis regarding the neurovascular role of [IL18R1](/details-gene/8809), an *in vitro* co-culture model of the human blood-brain barrier could be established using primary human cerebral microvascular endothelial cells grown on transwell inserts with primary human neurons cultured below. The impact of recombinant IL-18 on barrier integrity could be quantified by measuring trans-endothelial electrical resistance (TEER) and permeability to fluorescently-labeled dextrans. To establish causality, the experiment would be repeated following siRNA-mediated knockdown or CRISPR/Cas9 knockout of [IL18R1](/details-gene/8809) in the endothelial cells. The direct effect on neuronal function could be simultaneously assessed using calcium imaging or multi-electrode arrays to monitor changes in neuronal firing patterns in response to IL-18 stimulation. **Therapeutic Potential:** As a cell surface receptor that initiates potent pro-inflammatory signaling, [IL18R1](/details-gene/8809) represents a compelling therapeutic target for **inhibition**. Its activity is implicated in a wide range of inflammatory and autoimmune diseases. Blocking the IL-18/[IL18R1](/details-gene/8809) axis with monoclonal antibodies or small molecule inhibitors could be a viable strategy to ameliorate pathology in conditions characterized by excessive Th1-mediated inflammation, such as inflammatory bowel disease, rheumatoid arthritis, or acute graft-versus-host disease. Its expression on non-immune cells in the CNS also suggests potential utility in treating neuroinflammatory disorders.

Genular Protein ID: 3045351616

Symbol: IL18R_HUMAN

Name: Interleukin-18 receptor 1

UniProtKB Accession Codes:

Q13478 B2R9Y5 Q52LC9

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 5 ChEMBL 1 DNASU 1 DisGeNET 1 EC 1 EMBL 6 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 19 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 Rhea 2 SASBDB 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8626725

Title: IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP.

PubMed ID: 8626725

DOI: 10.1074/jbc.271.8.3967

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9325300

Title: Purification and characterization of the human interleukin-18 receptor.

PubMed ID: 9325300

DOI: 10.1074/jbc.272.41.25737

PubMed ID: 10653850

Title: IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells.

PubMed ID: 10653850

DOI: 10.1093/intimm/12.2.151

PubMed ID: 10925275

Title: IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells.

PubMed ID: 10925275

DOI: 10.4049/jimmunol.165.4.1933

PubMed ID: 11046021

Title: IL-18 receptors, their role in ligand binding and function: anti-IL-1RAcPL antibody, a potent antagonist of IL-18.

PubMed ID: 11046021

DOI: 10.4049/jimmunol.165.9.4950

PubMed ID: 14528293

Title: The structure and binding mode of interleukin-18.

PubMed ID: 14528293

DOI: 10.1038/nsb993

PubMed ID: 37993714

Title: Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome.

PubMed ID: 37993714

DOI: 10.1038/s41586-023-06742-w

PubMed ID: 25261253

Title: Structural basis for the specific recognition of IL-18 by its alpha receptor.

PubMed ID: 25261253

DOI: 10.1016/j.febslet.2014.09.019

PubMed ID: 25500532

Title: The structural basis for receptor recognition of human interleukin-18.

PubMed ID: 25500532

DOI: 10.1038/ncomms6340

Sequence Information:

  • Length: 541
  • Mass: 62304
  • Checksum: 7173DB9C7EA71D32
  • Sequence:
    • MNCRELPLTL WVLISVSTAE SCTSRPHITV VEGEPFYLKH CSCSLAHEIE TTTKSWYKSS 
GSQEHVELNP RSSSRIALHD CVLEFWPVEL NDTGSYFFQM KNYTQKWKLN VIRRNKHSCF 
TERQVTSKIV EVKKFFQITC ENSYYQTLVN STSLYKNCKK LLLENNKNPT IKKNAEFEDQ 
GYYSCVHFLH HNGKLFNITK TFNITIVEDR SNIVPVLLGP KLNHVAVELG KNVRLNCSAL 
LNEEDVIYWM FGEENGSDPN IHEEKEMRIM TPEGKWHASK VLRIENIGES NLNVLYNCTV 
ASTGGTDTKS FILVRKADMA DIPGHVFTRG MIIAVLILVA VVCLVTVCVI YRVDLVLFYR 
HLTRRDETLT DGKTYDAFVS YLKECRPENG EEHTFAVEIL PRVLEKHFGY KLCIFERDVV 
PGGAVVDEIH SLIEKSRRLI IVLSKSYMSN EVRYELESGL HEALVERKIK IILIEFTPVT 
DFTFLPQSLK LLKSHRVLKW KADKSLSYNS RFWKNLLYLM PAKTVKPGRD EPEVLPVLSE 
S