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    IL1RN interleukin 1 receptor antagonist [ Homo sapiens (human) ]

    Gene ID: 3557, updated on 14-Nov-2024

    Summary

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    Official Symbol
    IL1RNprovided by HGNC
    Official Full Name
    interleukin 1 receptor antagonistprovided by HGNC
    Primary source
    HGNC:HGNC:6000
    See related
    Ensembl:ENSG00000136689 MIM:147679; AllianceGenome:HGNC:6000
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DIRA; IRAP; CRMO2; IL1F3; IL1RA; MVCD4; IL-1RN; IL-1ra; IL-1ra3; ICIL-1RA
    Summary
    The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Biased expression in esophagus (RPKM 367.9), bone marrow (RPKM 53.9) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IL1RN in Genome Data Viewer
    Location:
    2q14.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (113099360..113134014)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (113544556..113560594)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (113875548..113891591)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:113835447-113836646 Neighboring gene interleukin 1 family member 10 Neighboring gene Sharpr-MPRA regulatory region 10370 Neighboring gene RNA, U6 small nuclear 1180, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16412 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11878 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11879 Neighboring gene Sharpr-MPRA regulatory region 7144 Neighboring gene uncharacterized LOC124907872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:113930391-113930891 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:113929890-113930390 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16414 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16415 Neighboring gene pleckstrin and Sec7 domain containing 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16416 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16417 Neighboring gene Sharpr-MPRA regulatory region 2961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16418 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11881 Neighboring gene paired box 8 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:113998497-113999696 Neighboring gene PAX8 antisense RNA 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Prognostic value of interleukin-1 receptor antagonist gene polymorphism and cytomegalovirus seroprevalence in patients with coronary artery disease. Rothenbacher D, et al. BMC Cardiovasc Disord, 2005 May 20. PMID 15943888, Free PMC Article
    2. Interleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth. Iglesias-Linares A, et al. Histol Histopathol, 2013 Jun. PMID 23212299
    3. Association of the IL1RN gene VNTR polymorphism with human male infertility. Jaiswal D, et al. PLoS One, 2012. PMID 23251650, Free PMC Article
    4. Anion binding and controlled aggregation of human interleukin-1 receptor antagonist. Raibekas AA, et al. Biochemistry, 2005 Jul 26. PMID 16026159
    5. [The association study of interleukin-1beta and interleukin-1 receptor antagonist and clinical symptoms of schizophrenia]. Golimbet VE, et al. Zh Nevrol Psikhiatr Im S S Korsakova, 2012. PMID 23388595

    See all (1000) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study.
      Title: IL27 and IL1RN are causally associated with acute pancreatitis: a Mendelian randomization study.
    2. Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.
      Title: Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.
    3. The Influence of Genetic Polymorphisms on the Expression of Interleukin-1beta, Prostaglandin E2 and Tumor Necrosis Factor Alpha in Peri-Implant Crevicular Fluid: A Cross-Sectional Study.
      Title: The Influence of Genetic Polymorphisms on the Expression of Interleukin-1beta, Prostaglandin E2 and Tumor Necrosis Factor Alpha in Peri-Implant Crevicular Fluid: A Cross-Sectional Study.
    4. Elevated IL-1beta and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players.
      Title: Elevated IL-1β and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players.
    5. Association of MIF-173G/C, IL-4 VNTR, and IL-1RA VNTR variants with FMF-related amyloidosis in a Turkish cohort.
      Title: Association of MIF-173G/C, IL-4 VNTR, and IL-1RA VNTR variants with FMF-related amyloidosis in a Turkish cohort.
    6. DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis.
      Title: DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis.
    7. Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis.
      Title: Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis.
    8. IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway.
      Title: IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway.
    9. The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia.
      Title: The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia.
    10. Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses.
      Title: Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses.
    Submit: New GeneRIF Correction See all GeneRIFs (561)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Gastric cancer
    MedGen: C0024623 OMIM: 613659 GeneReviews: Not available
    		Compare labs
    Microvascular complications of diabetes, susceptibility to, 4
    MedGen: C2675112 OMIM: 612628 GeneReviews: Not available
    		Compare labs
    Sterile multifocal osteomyelitis with periostitis and pustulosis
    MedGen: C2748507 OMIM: 612852 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    EBI GWAS Catalog
    Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women.
    EBI GWAS Catalog
    Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of interleukin 1 receptor antagonist (IL1RN) in human B cells PubMed
    Tat tat HIV-1 Tat upregulates the expression of IL-1 receptor antagonist through binding to and inhibiting CD26 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC10430

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables interleukin-1 receptor antagonist activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables interleukin-1 receptor antagonist activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables interleukin-1 receptor antagonist activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables interleukin-1 receptor binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables interleukin-1 type I receptor antagonist activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables interleukin-1 type II receptor antagonist activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables interleukin-1, type I receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables interleukin-1, type II receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in acute-phase response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in immune response NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of cytokine-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of heterotypic cell-cell adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of interleukin-1-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of interleukin-1-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to glucocorticoid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    interleukin-1 receptor antagonist protein
    Names
    IL1 inhibitor
    intracellular IL-1 receptor antagonist type II
    intracellular interleukin-1 receptor antagonist (icIL-1ra)
    type II interleukin-1 receptor antagonist

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_021240.1 RefSeqGene

      Range
      5001..21124
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_188

    mRNA and Protein(s)

    1. NM_000577.5 → NP_000568.1  interleukin-1 receptor antagonist protein isoform 3

      See identical proteins and their annotated locations for NP_000568.1

      Status: REVIEWED

      Source sequence(s)
      AC024704, BC009745, M55646
      Consensus CDS
      CCDS2113.1
      UniProtKB/Swiss-Prot
      P18510
      Related
      ENSP00000329072.3, ENST00000354115.6
      Conserved Domains (1) summary
      smart00125
      Location:16 → 156
      IL1; Interleukin-1 homologues

    2. NM_001318914.2 → NP_001305843.1  interleukin-1 receptor antagonist protein isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC024704, AF043143, BC009745, DA667440
      Consensus CDS
      CCDS2115.1
      Related
      ENSP00000512949.1, ENST00000696881.1
      Conserved Domains (1) summary
      smart00125
      Location:1 → 140
      IL1; Interleukin-1 homologues

    3. NM_001379360.1 → NP_001366289.1  interleukin-1 receptor antagonist protein isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC024704
      Consensus CDS
      CCDS2115.1
      Related
      ENSP00000512947.1, ENST00000696879.1
      Conserved Domains (1) summary
      smart00125
      Location:1 → 140
      IL1; Interleukin-1 homologues

    4. NM_173841.3 → NP_776213.1  interleukin-1 receptor antagonist protein isoform 2

      See identical proteins and their annotated locations for NP_776213.1

      Status: REVIEWED

      Source sequence(s)
      AC024704
      Consensus CDS
      CCDS2114.1
      UniProtKB/Swiss-Prot
      P18510
      Related
      ENSP00000259206.5, ENST00000259206.9
      Conserved Domains (1) summary
      smart00125
      Location:37 → 177
      IL1; Interleukin-1 homologues

    5. NM_173842.3 → NP_776214.1  interleukin-1 receptor antagonist protein isoform 1 precursor

      See identical proteins and their annotated locations for NP_776214.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' end compared to variant 2, resulting in an isoform (1) that has a distinct and shorter N-terminus, as compared to the longest isoform (2).
      Source sequence(s)
      AC024704, BC009745, BI766516
      Consensus CDS
      CCDS46396.1
      UniProtKB/Swiss-Prot
      A8K4G1, P18510, Q14628, Q53SC2, Q7RTZ4, Q96GD6, Q9UPC0
      Related
      ENSP00000387173.3, ENST00000409930.4
      Conserved Domains (1) summary
      smart00125
      Location:34 → 174
      IL1; Interleukin-1 homologues

    6. NM_173843.3 → NP_776215.1  interleukin-1 receptor antagonist protein isoform 4

      See identical proteins and their annotated locations for NP_776215.1

      Status: REVIEWED

      Source sequence(s)
      AC024704, AF043143, BC009745
      Consensus CDS
      CCDS2115.1
      Related
      ENSP00000354816.3, ENST00000361779.7
      Conserved Domains (1) summary
      smart00125
      Location:1 → 140
      IL1; Interleukin-1 homologues

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      113099360..113134014
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047444184.1 → XP_047300140.1  interleukin-1 receptor antagonist protein isoform X1

    2. XM_047444185.1 → XP_047300141.1  interleukin-1 receptor antagonist protein isoform X1

    3. XM_011511121.2 → XP_011509423.1  interleukin-1 receptor antagonist protein isoform X1

      See identical proteins and their annotated locations for XP_011509423.1

      Related
      ENSP00000387210.1, ENST00000409052.6
      Conserved Domains (1) summary
      smart00125
      Location:1 → 140
      IL1; Interleukin-1 homologues

    4. XM_047444186.1 → XP_047300142.1  interleukin-1 receptor antagonist protein isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      113544556..113560594
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P18510.1 GenPept UniProtKB/Swiss-Prot:P18510

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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