Human Gene IL1RN (ENST00000409930.4) from GENCODE V44
  Description: Homo sapiens interleukin 1 receptor antagonist (IL1RN), transcript variant 1, mRNA. (from RefSeq NM_173842)
RefSeq Summary (NM_173842): 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. 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, Jan 2016].
Gencode Transcript: ENST00000409930.4
Gencode Gene: ENSG00000136689.20
Transcript (Including UTRs)
   Position: hg38 chr2:113,127,598-113,134,014 Size: 6,417 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg38 chr2:113,127,625-113,132,871 Size: 5,247 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:113,127,598-113,134,014)mRNA (may differ from genome)Protein (177 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: IL1RA_HUMAN
DESCRIPTION: RecName: Full=Interleukin-1 receptor antagonist protein; Short=IL-1RN; Short=IL-1ra; Short=IRAP; AltName: Full=ICIL-1RA; AltName: Full=IL1 inhibitor; AltName: INN=Anakinra; Flags: Precursor;
FUNCTION: Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.
SUBCELLULAR LOCATION: Isoform 1: Secreted.
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
SUBCELLULAR LOCATION: Isoform 4: Cytoplasm.
TISSUE SPECIFICITY: The intracellular form of IL1RN is predominantly expressed in epithelial cells.
DISEASE: Genetic variation in IL1RN is associated with susceptibility to microvascular complications of diabetes type 4 (MVCD4) [MIM:612628]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new- onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
DISEASE: Defects in IL1RN are the cause of interleukin 1 receptor antagonist deficiency (DIRA) [MIM:612852]; also known as deficiency of interleukin 1 receptor antagonist. Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T-cells. DIRA is a rare, autosomal recessive, genetic autoinflammatory disease that results in sterile multifocal osteomyelitis (bone inflammation in multiple places), periostitis (inflammation of the membrane surrounding the bones), and pustulosis (due to skin inflammation) from birth.
PHARMACEUTICAL: Available under the name Kineret (Amgen). Used for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis.
WEB RESOURCE: Name=R&D Systems' cytokine source book: IL-1ra; URL="http://www.rndsystems.com/molecule_detail.aspx?m=1637";
WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry; URL="http://en.wikipedia.org/wiki/Interleukin_1";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/il1rn/";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=IL1RN";
WEB RESOURCE: Name=Kineret professional medical information"; URL="http://www.rxlist.com/kineret-drug.htm";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: IL1RN
Diseases sorted by gene-association score: interleukin 1 receptor antagonist deficiency* (1370), microvascular complications of diabetes 4* (594), gastric cancer risk after h. pylori infection* (389), periostitis (24), osteomyelitis (23), atrophic gastritis (21), schnitzler syndrome (18), duodenal ulcer (17), adult-onset still's disease (13), alopecia areata (13), cryopyrin-associated periodic syndrome (13), acute cholangitis (12), silicosis (11), cinca syndrome (11), rheumatoid arthritis (10), acne (10), exanthem (10), pericardium disease (10), aphthous stomatitis (9), vulvar vestibulitis syndrome (9), constrictive pericarditis (9), pouchitis (9), aseptic meningitis (9), aggressive periodontitis (8), gastritis (8), root resorption (8), mevalonic aciduria (7), bronchopulmonary dysplasia (7), pars planitis (7), synovitis (7), hyper-igd syndrome (7), idiopathic neutropenia (7), gastric ulcer (7), peptic ulcer disease (7), histiocytosis (7), arthritis (7), cerebral artery occlusion (7), temporal arteritis (7), rheumatoid arthritis, systemic juvenile (6), necrotizing fasciitis (6), chondromalacia (6), anterior scleritis (6), meningococcemia (6), dengue shock syndrome (6), brucellosis (6), pseudopapilledema (6), joint disorders (6), yellow fever (6), sweat gland disease (5), somatoform disorder (5), hydrarthrosis (5), scleral disease (5), non-langerhans-cell histiocytosis (5), extrapulmonary tuberculosis (5), cartilage disease (5), acute hemorrhagic leukoencephalitis (5), spondyloarthropathy 1 (5), neisseria meningitidis infection (5), bone inflammation disease (4), omenn syndrome (4), hypersensitivity reaction type iv disease (4), osteosclerotic myeloma (4), periodontal disease (4), sudden infant death syndrome (4), ischemia (3), osteoporosis (2), malaria (2), autoinflammation, lipodystrophy, and dermatosis syndrome (2), eye disease (2), pulmonary fibrosis, idiopathic (1), west syndrome (1), gastric cancer, somatic (1), behcet syndrome (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 700.22 RPKM in Esophagus - Mucosa
Total median expression: 1047.16 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -5.3027-0.196 Picture PostScript Text
3' UTR -344.001143-0.301 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008996 - Cytokine_IL1-like
IPR003297 - IL_rcpt_IL1RA
IPR020877 - Interleukin-1_CS
IPR000975 - Interleukin_1

Pfam Domains:
PF00340 - Interleukin-1 / 18

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1ILR - X-ray MuPIT 1ILT - X-ray MuPIT 1IRA - X-ray MuPIT 1IRP - NMR MuPIT 1ITN - Model 2IRT - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P18510
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005125 cytokine activity
GO:0005149 interleukin-1 receptor binding
GO:0005150 interleukin-1, Type I receptor binding
GO:0005151 interleukin-1, Type II receptor binding
GO:0005152 interleukin-1 receptor antagonist activity
GO:0005515 protein binding
GO:0045352 interleukin-1 Type I receptor antagonist activity
GO:0045353 interleukin-1 Type II receptor antagonist activity

Biological Process:
GO:0001660 fever generation
GO:0001960 negative regulation of cytokine-mediated signaling pathway
GO:0006629 lipid metabolic process
GO:0006953 acute-phase response
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0010469 regulation of receptor activity
GO:0019221 cytokine-mediated signaling pathway
GO:0030073 insulin secretion
GO:0034115 negative regulation of heterotypic cell-cell adhesion
GO:0051384 response to glucocorticoid
GO:0070498 interleukin-1-mediated signaling pathway
GO:2000660 negative regulation of interleukin-1-mediated signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0031982 vesicle
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BC068441 - Homo sapiens interleukin 1 receptor antagonist, mRNA (cDNA clone IMAGE:5270437), partial cds.
AF043143 - Homo sapiens interleukin-1 intracellular receptor antagonist variant (IL1RN) mRNA, partial cds.
M55646 - Human icIL-1ra mRNA, complete cds.
AK290898 - Homo sapiens cDNA FLJ75678 complete cds, highly similar to Homo sapiens interleukin 1 receptor antagonist (IL1RN), transcript variant 2, mRNA.
X84348 - H.sapiens mRNA for intracellular IL-1 receptor antagonist type II.
BC009745 - Homo sapiens interleukin 1 receptor antagonist, mRNA (cDNA clone MGC:10430 IMAGE:3689284), complete cds.
MP067515 - Sequence 19 from Patent WO2018232288.
AK290926 - Homo sapiens cDNA FLJ77102 complete cds, highly similar to Homo sapiens interleukin 1 receptor antagonist (IL1RN), transcript variant 1, mRNA.
X52015 - H.sapiens mRNA for interleukin-1 receptor antagonist.
X53296 - H.sapiens mRNA for IRAP.
DQ895781 - Synthetic construct Homo sapiens clone IMAGE:100010241; FLH187595.01L; RZPDo839B02149D interleukin 1 receptor antagonist (IL1RN) gene, encodes complete protein.
AB529162 - Synthetic construct DNA, clone: pF1KB6875, Homo sapiens IL1RN gene for interleukin 1 receptor antagonist, without stop codon, in Flexi system.
KJ897043 - Synthetic construct Homo sapiens clone ccsbBroadEn_06437 IL1RN gene, encodes complete protein.
DQ892566 - Synthetic construct clone IMAGE:100005196; FLH187599.01X; RZPDo839B02150D interleukin 1 receptor antagonist (IL1RN) gene, encodes complete protein.
JD137741 - Sequence 118765 from Patent EP1572962.
JD022596 - Sequence 3620 from Patent EP1572962.
JD032196 - Sequence 13220 from Patent EP1572962.
JD139211 - Sequence 120235 from Patent EP1572962.
JD457288 - Sequence 438312 from Patent EP1572962.
JD118981 - Sequence 100005 from Patent EP1572962.
JD375215 - Sequence 356239 from Patent EP1572962.
JD226456 - Sequence 207480 from Patent EP1572962.
JD125458 - Sequence 106482 from Patent EP1572962.
JD544305 - Sequence 525329 from Patent EP1572962.
JD177902 - Sequence 158926 from Patent EP1572962.
JD042544 - Sequence 23568 from Patent EP1572962.
JD396984 - Sequence 378008 from Patent EP1572962.
JD036883 - Sequence 17907 from Patent EP1572962.
JD054728 - Sequence 35752 from Patent EP1572962.
JD456415 - Sequence 437439 from Patent EP1572962.
JD400082 - Sequence 381106 from Patent EP1572962.
JD154098 - Sequence 135122 from Patent EP1572962.
JD189834 - Sequence 170858 from Patent EP1572962.
JD153947 - Sequence 134971 from Patent EP1572962.
JD261319 - Sequence 242343 from Patent EP1572962.
JD101575 - Sequence 82599 from Patent EP1572962.
JD079722 - Sequence 60746 from Patent EP1572962.
JD131072 - Sequence 112096 from Patent EP1572962.
JD102862 - Sequence 83886 from Patent EP1572962.
JD426387 - Sequence 407411 from Patent EP1572962.
JD295479 - Sequence 276503 from Patent EP1572962.
JD204865 - Sequence 185889 from Patent EP1572962.
JD226220 - Sequence 207244 from Patent EP1572962.
JD133083 - Sequence 114107 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_il1rPathway - Signal transduction through IL1R

Reactome (by CSHL, EBI, and GO)

Protein P18510 (Reactome details) participates in the following event(s):

R-HSA-445757 IL1 receptor antagonist protein binds Interleukin 1 receptors
R-HSA-9020702 Interleukin-1 signaling
R-HSA-6783783 Interleukin-10 signaling
R-HSA-446652 Interleukin-1 family signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8K4G1, ENST00000409930.1, ENST00000409930.2, ENST00000409930.3, IL1F3, IL1RA, IL1RA_HUMAN, NM_173842, P18510, Q14628, Q53SC2, Q7RTZ4, Q96GD6, Q9UPC0, uc002tjb.1, uc002tjb.2, uc002tjb.3, uc002tjb.4, uc002tjb.5
UCSC ID: ENST00000409930.4
RefSeq Accession: NM_173842
Protein: P18510 (aka IL1RA_HUMAN or IL1X_HUMAN)
CCDS: CCDS46396.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.