The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through w... See more...

Aliases for IL37 Gene

Aliases for IL37 Gene

  • Interleukin 37 2 3 5
  • Interleukin-1-Related Protein 2 3 4
  • Interleukin-1 Homolog 4 2 3 4
  • IL-1RP1 2 3 4
  • IL-1F7 2 3 4
  • IL-1H4 2 3 4
  • FIL1Z 2 3 4
  • Interleukin 1, Zeta 2 3
  • Interleukin-37 3 4
  • Interleukin-23 3 4
  • FIL1(ZETA) 2 3
  • FIL1 Zeta 3 4
  • IL-1 Zeta 3 4
  • IL1RP1 3 4
  • IL-1H 3 4
  • IL-23 3 4
  • IL-37 3 4
  • IL1F7 3 4
  • IL1H4 3 4
  • FIL1 2 3
  • Interleukin 1 Family, Member 7 (Zeta) 2
  • IL1F7 (Canonical Product IL-1F7b) 3
  • IL-1F7b (IL-1H4, IL-1H, IL-1RP1) 3
  • Interleukin 1 Family Member 7 3
  • Interleukin-1 Family Member 7 4
  • Interleukin-1 Superfamily Z 3
  • Interleukin-1 Zeta 4
  • IL-1X Protein 3
  • IL-1X 4
  • IL37 5

External Ids for IL37 Gene

Previous HGNC Symbols for IL37 Gene

  • IL1F7

Previous GeneCards Identifiers for IL37 Gene

  • GC02P113672
  • GC02P112912
  • GC02P113966
  • GC02P114219
  • GC02P114257
  • GC02P114902
  • GC02P112914
  • GC02P113041
  • GC02P113142
  • GC02P113366
  • GC02P113606
  • GC02P113833
  • GC02P115304
  • GC02P115719

Summaries for IL37 Gene

Entrez Gene Summary for IL37 Gene

  • The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18. This gene along with eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

GeneCards Summary for IL37 Gene

IL37 (Interleukin 37) is a Protein Coding gene. Diseases associated with IL37 include Adult-Onset Still's Disease and Idiopathic Anterior Uveitis. Among its related pathways are Cytokine Signaling in Immune system and Toll-Like receptor Signaling Pathways. Gene Ontology (GO) annotations related to this gene include cytokine activity and interleukin-1 receptor binding. An important paralog of this gene is IL36G.

UniProtKB/Swiss-Prot Summary for IL37 Gene

  • Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.

Gene Wiki entry for IL37 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IL37 Gene

Genomics for IL37 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IL37 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J112911 Promoter 0.3 EPDnew 250.7 0.0 -19 0.1 IL37 HSALNG0018010 IL1B
GH02J112875 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 16.6 -30.3 -30250 11 BCLAF1 SP1 ZNF207 ZNF654 ZNF580 CEBPA NFIC ZIC2 CHD4 BCL11A lnc-IL1B-2 piR-47728 IL1B IL1RN IL1A IL36B IL37 IL36G CKAP2L CDK8P2
GH02J112781 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 14.5 -127.5 -127531 3.9 POLR2A BCL11A CEBPB ZNF592 MAX ARNT KLF9 ZNF316 TBP EBF1 IL1A JA662187 IL37 IL1B ENSG00000243389 CHCHD5 ENSG00000207383 piR-41306-146 CKAP2L HSALNG0017997
GH02J112811 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 15.3 -97.9 -97930 4.5 BCLAF1 SP1 BCL11A TARDBP TRIM22 HOMEZ NR2C1 SMAD4 IRF4 ETV4 HSALNG0018001-002 IL1B IL1RN IL1A IL37 IL36B IL36G CKAP2L IL36RN HSALNG0018001-001
GH02J112720 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.2 -186.0 -185964 11.2 BCLAF1 ZNF654 MYC NCOR1 IKZF1 ZNF592 ZMYM3 CEBPA NFIC ZBTB10 NT5DC4 ENSG00000237753 ANAPC1 SLC20A1 ENSG00000231747 ENSG00000243389 CHCHD5 ENSG00000207383 TMEM87B IL1B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IL37 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IL37

Genomic Locations for IL37 Gene

Latest Assembly
chr2:112,911,165-112,918,882
(GRCh38/hg38)
Size:
7,718 bases
Orientation:
Plus strand

Previous Assembly
chr2:113,668,742-113,676,459
(GRCh37/hg19 by Entrez Gene)
Size:
7,718 bases
Orientation:
Plus strand

chr2:113,670,548-113,676,459
(GRCh37/hg19 by Ensembl)
Size:
5,912 bases
Orientation:
Plus strand

Genomic View for IL37 Gene

Genes around IL37 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IL37 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IL37 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IL37 Gene

Proteins for IL37 Gene

  • Protein details for IL37 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NZH6-IL37_HUMAN
    Recommended name:
    Interleukin-37
    Protein Accession:
    Q9NZH6
    Secondary Accessions:
    • B5BU97
    • Q56AP9
    • Q8TD04
    • Q8TD05
    • Q9HBF2
    • Q9HBF3
    • Q9UHA6

    Protein attributes for IL37 Gene

    Size:
    218 amino acids
    Molecular mass:
    24126 Da
    Quaternary structure:
    • Interacts with SMAD3. Binds IL18R1, but not to IL1R1, with lower affinity than IL18, and does not seem to act as a receptor antagonist for IL18. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
    Miscellaneous:
    • [Isoform B]: The name IL-HL refers to isoform B containing polymorphisms Val-31 and Ala-42.

    Three dimensional structures from OCA and Proteopedia for IL37 Gene

    Alternative splice isoforms for IL37 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IL37 Gene

Post-translational modifications for IL37 Gene

  • Proteolytically converted to the mature form by CASP1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Assay products for research

  • Boster Bio ELISA Kits for IL37
  • Abcam assays for IL37

No data available for DME Specific Peptides for IL37 Gene

Domains & Families for IL37 Gene

Gene Families for IL37 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for IL37 Gene

InterPro:
Blocks:
  • Interleukin-1 precursor family signature

Suggested Antigen Peptide Sequences for IL37 Gene

GenScript: Design optimal peptide antigens:
  • Interleukin-23 (IL37_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NZH6

UniProtKB/Swiss-Prot:

IL37_HUMAN :
  • Belongs to the IL-1 family.
Family:
  • Belongs to the IL-1 family.
genes like me logo Genes that share domains with IL37: view

Function for IL37 Gene

Molecular function for IL37 Gene

UniProtKB/Swiss-Prot Function:
Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.
UniProtKB/Swiss-Prot Induction:
Highly induced by bacterial lipopolysaccharides (LPS) and TGFB1, more moderately by IFNG, IL18, IL1B, TNF and the dinucleotide CpG (at protein level). Constitutive expression in bone marrow macrophages is down-regulated in the presence of IL4 and CSF2. Induced by phorbol myristate acetate (PMA) in different cell lines.

Phenotypes From GWAS Catalog for IL37 Gene

Gene Ontology (GO) - Molecular Function for IL37 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IBA 21873635
GO:0005149 interleukin-1 receptor binding TAS 10625660
GO:0005515 protein binding IPI 32296183
genes like me logo Genes that share ontologies with IL37: view

Phenotypes for IL37 Gene

genes like me logo Genes that share phenotypes with IL37: view

miRNA for IL37 Gene

miRTarBase miRNAs that target IL37

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL37

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for IL37 Gene

Localization for IL37 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IL37 Gene

Cytoplasm, cytosol. Nucleus. Secreted. Note=Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions (PubMed:20935647). Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation (PubMed:18390730). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059). {ECO:0000269 PubMed:32272059}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IL37 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
plasma membrane 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IL37 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS 10744718
GO:0005615 extracellular space IBA 21873635
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with IL37: view

Pathways & Interactions for IL37 Gene

genes like me logo Genes that share pathways with IL37: view

Pathways by source for IL37 Gene

Gene Ontology (GO) - Biological Process for IL37 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002437 inflammatory response to antigenic stimulus IBA 21873635
GO:0006954 inflammatory response IBA 21873635
GO:0006955 immune response NAS 10625660
GO:0010628 positive regulation of gene expression IBA 21873635
GO:0019221 cytokine-mediated signaling pathway IBA 21873635
genes like me logo Genes that share ontologies with IL37: view

No data available for SIGNOR curated interactions for IL37 Gene

Drugs & Compounds for IL37 Gene

(1) Drugs for IL37 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ustekinumab Approved, Investigational Pharma antibody 157
genes like me logo Genes that share compounds with IL37: view

Transcripts for IL37 Gene

mRNA/cDNA for IL37 Gene

5 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL37

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for IL37 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b
SP1: -
SP2: - -
SP3:
SP4: - - -
SP5: - -

Relevant External Links for IL37 Gene

GeneLoc Exon Structure for
IL37

Expression for IL37 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IL37 Gene

mRNA differential expression in normal tissues according to GTEx for IL37 Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x28.2) and Skin - Not Sun Exposed (Suprapubic) (x22.9).

Protein differential expression in normal tissues from HIPED for IL37 Gene

This gene is overexpressed in Lung (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for IL37 Gene



Protein tissue co-expression partners for IL37 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IL37

SOURCE GeneReport for Unigene cluster for IL37 Gene:

Hs.166371

mRNA Expression by UniProt/SwissProt for IL37 Gene:

Q9NZH6-IL37_HUMAN
Tissue specificity: In general, low constitutive expression, if any, in healthy tissues; high expression in inflammatory counterparts, including in synovial tissues from individuals with active rheumatoid arthritis. Isoform A, isoform B and isoform C are expressed in testis, colon, placenta, lung and lymph node. Isoform D and isoform E were found only in testis and bone marrow. Whereas only isoform A is found in brain, only isoform B in kidney and only isoform C in heart.

Evidence on tissue expression from TISSUES for IL37 Gene

  • Blood(4.4)
  • Intestine(4.3)
  • Lung(4.3)
  • Skin(2.8)
genes like me logo Genes that share expression patterns with IL37: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for IL37 Gene

Orthologs for IL37 Gene

This gene was present in the common ancestor of chordates.

Orthologs for IL37 Gene

Organism Taxonomy Gene Similarity Type Details
Dog
(Canis familiaris)
Mammalia IL37 29 30
  • 81.38 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IL37 29 30
  • 73.81 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 34 (a)
ManyToMany
-- 30
  • 30 (a)
ManyToMany
-- 30
  • 29 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 27 (a)
ManyToMany
-- 30
  • 27 (a)
ManyToMany
-- 30
  • 26 (a)
ManyToMany
-- 30
  • 23 (a)
ManyToMany
Species where no ortholog for IL37 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Mouse (Mus musculus)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for IL37 Gene

ENSEMBL:
Gene Tree for IL37 (if available)
TreeFam:
Gene Tree for IL37 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IL37: view image
Alliance of Genome Resources:
Additional Orthologs for IL37

Paralogs for IL37 Gene

Paralogs for IL37 Gene

(2) SIMAP similar genes for IL37 Gene using alignment to 1 proteins:

  • IL37_HUMAN
genes like me logo Genes that share paralogs with IL37: view

Variants for IL37 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IL37 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs139354551 Likely Benign: not provided 112,917,258(+) A/C
NM_014439.3(IL37):c.265+10A>C
INTRON
rs28947200 Benign: not provided 112,918,606(+) C/Tp.Arg152Trp
NM_014439.3(IL37):c.454C>T (p.Arg152Trp)
MISSENSE
rs3811047 Benign: not provided 112,913,833(+) A/Gp.Thr42Ala
NM_014439.3(IL37):c.124A>G (p.Thr42Ala)
MISSENSE_VARIANT,INTRON
rs2708943 -- p.Pro50Arg
rs2708947 -- p.Trp164Arg

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for IL37 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for IL37 Gene

Variant ID Type Subtype PubMed ID
esv3584019 CNV loss 25503493
nsv1003372 CNV loss 25217958
nsv2879 CNV insertion 18451855

Variation tolerance for IL37 Gene

Residual Variation Intolerance Score: 81% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.54; 82.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IL37 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
IL37
Leiden Open Variation Database (LOVD)
IL37

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IL37 Gene

Disorders for IL37 Gene

MalaCards: The human disease database

(9) MalaCards diseases for IL37 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
adult-onset still's disease
  • adult onset still's disease
idiopathic anterior uveitis
  • anterior uveitis idiopathic
eumycotic mycetoma
  • eumycetoma
dermatomycosis
  • dermatomycoses
rheumatoid arthritis
  • ra
- elite association - COSMIC cancer census association via MalaCards
Search IL37 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for IL37

genes like me logo Genes that share disorders with IL37: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IL37 Gene

Publications for IL37 Gene

  1. Four new members expand the interleukin-1 superfamily. (PMID: 10625660) Smith DE … Sims JE (The Journal of biological chemistry 2000) 2 3 4 22
  2. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. (PMID: 18390730) Sharma S … Bufler P (Journal of immunology (Baltimore, Md. : 1950) 2008) 3 4 22
  3. IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. (PMID: 11145836) Pan G … Vandlen R (Cytokine 2001) 3 4 22
  4. IL-37 is a fundamental inhibitor of innate immunity. (PMID: 20935647) Nold MF … Dinarello CA (Nature immunology 2010) 3 4
  5. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PMID: 15815621) Hillier LW … Wilson RK (Nature 2005) 3 4

Products for IL37 Gene

Sources for IL37 Gene