This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays... See more...

Aliases for IL21 Gene

Aliases for IL21 Gene

  • Interleukin 21 2 3 5
  • IL-21 2 3 4
  • Za11 2 3 4
  • Interleukin-21 3 4
  • CVID11 3
  • IL21 5

External Ids for IL21 Gene

Previous GeneCards Identifiers for IL21 Gene

  • GC04M124446
  • GC04M123813
  • GC04M123926
  • GC04M123992
  • GC04M123891
  • GC04M123534
  • GC04M119260

Summaries for IL21 Gene

Entrez Gene Summary for IL21 Gene

  • This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GeneCards Summary for IL21 Gene

IL21 (Interleukin 21) is a Protein Coding gene. Diseases associated with IL21 include Immunodeficiency, Common Variable, 11 and Inflammatory Bowel Disease 25, Autosomal Recessive. Among its related pathways are PEDF Induced Signaling and Akt Signaling. Gene Ontology (GO) annotations related to this gene include cytokine activity and interleukin-2 receptor binding.

UniProtKB/Swiss-Prot Summary for IL21 Gene

  • Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). Implicated in the generation and maintenance of T follicular helper (Tfh) cells and the formation of germinal-centers. Together with IL6, control the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells (PubMed:11081504, PubMed:15178704). During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation (By similarity).

Gene Wiki entry for IL21 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IL21 Gene

Genomics for IL21 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IL21 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
GH04J122621 Promoter 0.3 EPDnew 250.7 0.0 -20 0.1 HSALNG0036853 IL21 piR-39098-183 IL21-AS1 BBS12
GH04J122665 Enhancer 0.7 Ensembl ENCODE 11 -46.3 -46281 4.7 JUND CEBPB EP300 TCF7L2 L3MBTL2 POLR2A DACH1 FOS IL21 IL21-AS1 FGF2 piR-39098-183 BBS12
GH04J122150 Promoter/Enhancer 2 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 1.1 +469.0 469001 3.9 SP1 MYC ZNF600 KLF9 POLR2A ZIC2 YY1 SMAD5 SIN3A TBP KIAA1109 HSALNG0036842 lnc-KIAA1109-1 lnc-TRPC3-4 IL2 IL21 piR-34822-252 TRPC3
GH04J122729 Enhancer 0.2 Ensembl 10.6 -108.0 -108035 0.2 HSALNG0036858 IL21 NUDT6 SPATA5 IL21-AS1 CETN4P lnc-IL21-1 BBS12 FGF2
GH04J122602 Enhancer 1 Ensembl ENCODE 0.4 +17.6 17566 2.6 ZNF654 ZNF592 REST TRIM22 CTCF NBN RAD21 SMC3 TAL1 YY1 HSALNG0036854 NUDT6 SPATA5 KIAA1109 IL21 piR-48553-226 IL21-AS1 IL2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IL21 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IL21

Top Transcription factor binding sites by QIAGEN in the IL21 gene promoter:
  • C/EBPalpha
  • GR
  • GR-alpha
  • GR-beta
  • HTF
  • NF-AT
  • NF-AT1
  • NF-AT2
  • Pbx1a
  • STAT3

Genomic Locations for IL21 Gene

Latest Assembly
chr4:122,610,108-122,621,066
(GRCh38/hg38)
Size:
10,959 bases
Orientation:
Minus strand

Previous Assembly
chr4:123,531,263-123,542,221
(GRCh37/hg19 by Entrez Gene)
Size:
10,959 bases
Orientation:
Minus strand

chr4:123,533,783-123,542,224
(GRCh37/hg19 by Ensembl)
Size:
8,442 bases
Orientation:
Minus strand

Genomic View for IL21 Gene

Genes around IL21 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IL21 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IL21 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IL21 Gene

Proteins for IL21 Gene

  • Protein details for IL21 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HBE4-IL21_HUMAN
    Recommended name:
    Interleukin-21
    Protein Accession:
    Q9HBE4
    Secondary Accessions:
    • A5J0L4

    Protein attributes for IL21 Gene

    Size:
    162 amino acids
    Molecular mass:
    18653 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for IL21 Gene

    Alternative splice isoforms for IL21 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IL21 Gene

Post-translational modifications for IL21 Gene

  • Glycosylation at Asn97
  • Modification sites at PhosphoSitePlus

Other Protein References for IL21 Gene

Antibodies for research

  • Abcam antibodies for IL21

No data available for DME Specific Peptides for IL21 Gene

Domains & Families for IL21 Gene

Gene Families for IL21 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for IL21 Gene

Suggested Antigen Peptide Sequences for IL21 Gene

GenScript: Design optimal peptide antigens:
  • Za11 (IL21_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HBE4

UniProtKB/Swiss-Prot:

IL21_HUMAN :
  • Belongs to the IL-15/IL-21 family.
Family:
  • Belongs to the IL-15/IL-21 family.
genes like me logo Genes that share domains with IL21: view

Function for IL21 Gene

Molecular function for IL21 Gene

UniProtKB/Swiss-Prot Function:
Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). Implicated in the generation and maintenance of T follicular helper (Tfh) cells and the formation of germinal-centers. Together with IL6, control the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells (PubMed:11081504, PubMed:15178704). During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation (By similarity).

Phenotypes From GWAS Catalog for IL21 Gene

Gene Ontology (GO) - Molecular Function for IL21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IEA --
GO:0005126 cytokine receptor binding TAS 15546387
GO:0005134 interleukin-2 receptor binding IPI 12504082
GO:0005515 protein binding IPI 32296183
genes like me logo Genes that share ontologies with IL21: view
genes like me logo Genes that share phenotypes with IL21: view

Human Phenotype Ontology for IL21 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for IL21 Gene

MGI Knock Outs for IL21:

Animal Models for research

  • Taconic Biosciences Mouse Models for IL21

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL21

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for IL21 Gene

Localization for IL21 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IL21 Gene

Secreted.

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 IL21 gene
Compartment Confidence
extracellular 5
plasma membrane 2
nucleus 2
cytoskeleton 1
mitochondrion 1
endosome 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for IL21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space NAS 11081504
genes like me logo Genes that share ontologies with IL21: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for IL21 Gene

Pathways & Interactions for IL21 Gene

PathCards logo

SuperPathways for IL21 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.47
.46
2 ERK Signaling
.61
.61
.51
3 Th17 cell differentiation
4 Th17 Differentiation Pathway
5 Akt Signaling
.60
.60
genes like me logo Genes that share pathways with IL21: view

Pathways by source for IL21 Gene

1 GeneGo (Thomson Reuters) pathway for IL21 Gene
  • Cytokine production by Th17 cells in CF (Mouse model)
15 Qiagen pathways for IL21 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway
  • ERK Signaling

Interacting Proteins for IL21 Gene

SIGNOR curated interactions for IL21 Gene

Activates:

Gene Ontology (GO) - Biological Process for IL21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001819 positive regulation of cytokine production IDA 19322899
GO:0002314 germinal center B cell differentiation ISS --
GO:0002377 immunoglobulin production ISS --
GO:0006955 immune response IEA --
GO:0007165 signal transduction NAS 11081504
genes like me logo Genes that share ontologies with IL21: view

Drugs & Compounds for IL21 Gene

(2) Drugs for IL21 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for IL21 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IL21: view

Transcripts for IL21 Gene

mRNA/cDNA for IL21 Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
3 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 IL21

Alternative Splicing Database (ASD) splice patterns (SP) for IL21 Gene

No ASD Table

Relevant External Links for IL21 Gene

GeneLoc Exon Structure for
IL21

Expression for IL21 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IL21 Gene

mRNA differential expression in normal tissues according to GTEx for IL21 Gene

This gene is overexpressed in Testis (x41.3).

Protein differential expression in normal tissues from HIPED for IL21 Gene

This gene is overexpressed in Testis (23.6), Adrenal (19.9), Heart (12.1), and Stomach (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for IL21 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IL21

SOURCE GeneReport for Unigene cluster for IL21 Gene:

Hs.567559

mRNA Expression by UniProt/SwissProt for IL21 Gene:

Q9HBE4-IL21_HUMAN
Tissue specificity: Expressed in activated CD4-positive T-cells but not in CD8-positive T-cells, B-cells, or monocytes.

Evidence on tissue expression from TISSUES for IL21 Gene

  • Lymph node(2.5)
  • Blood(2.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for IL21 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • reproductive
  • respiratory
Regions:
Abdomen:
  • intestine
  • large intestine
  • small intestine
  • stomach
Pelvis:
  • anus
  • rectum
  • vagina
General:
  • blood
  • bone marrow
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with IL21: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for IL21 Gene

Orthologs for IL21 Gene

This gene was present in the common ancestor of chordates.

Orthologs for IL21 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia IL21 29 30
  • 99.59 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia IL21 29 30
  • 89.04 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IL21 29 30
  • 87.92 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Il21 29 16 30
  • 76.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Il21 29
  • 75.8 (n)
Oppossum
(Monodelphis domestica)
Mammalia IL21 30
  • 45 (a)
OneToOne
Chicken
(Gallus gallus)
Aves IL21 30
  • 30 (a)
OneToOne
Species where no ortholog for IL21 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)
  • 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)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • 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 IL21 Gene

ENSEMBL:
Gene Tree for IL21 (if available)
TreeFam:
Gene Tree for IL21 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IL21: view image
Alliance of Genome Resources:
Additional Orthologs for IL21

Paralogs for IL21 Gene

No data available for Paralogs for IL21 Gene

Variants for IL21 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IL21 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
1041152 Uncertain Significance: not provided 122,620,975(-) T/C
NM_021803.4(IL21):c.37A>G (p.Ile13Val)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1047806 Uncertain Significance: not provided 122,615,705(-) C/T
NM_021803.4(IL21):c.337G>A (p.Gly113Arg)
MISSENSE
854415 Uncertain Significance: not provided 122,620,929(-) C/T
NM_021803.4(IL21):c.83G>A (p.Ser28Asn)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
856120 Uncertain Significance: not provided 122,615,765(-) C/T
NM_021803.4(IL21):c.277G>A (p.Glu93Lys)
MISSENSE
858592 Uncertain Significance: not provided 122,612,724(-) T/G
NM_021803.4(IL21):c.475A>C (p.Ser159Arg)
MISSENSE_VARIANT,THREE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for IL21 Gene

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

Variation tolerance for IL21 Gene

Residual Variation Intolerance Score: 48.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.09; 2.05% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IL21 Gene

Human Gene Mutation Database (HGMD)
IL21
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IL21
Leiden Open Variation Database (LOVD)
IL21

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for IL21 Gene

Disorders for IL21 Gene

MalaCards: The human disease database

(16) MalaCards diseases for IL21 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search IL21 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

IL21_HUMAN
  • Immunodeficiency, common variable, 11 (CVID11) [MIM:615767]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269 PubMed:24746753}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for IL21

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with IL21: view

No data available for Genatlas for IL21 Gene

Publications for IL21 Gene

  1. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. (PMID: 24746753) Salzer E … Boztug K (The Journal of allergy and clinical immunology 2014) 3 4 72
  2. Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. (PMID: 17720724) Sawalha AH … Harley JB (Annals of the rheumatic diseases 2008) 3 22 40
  3. Molecular scanning of interleukin-21 gene and genetic susceptibility to type 1 diabetes. (PMID: 17462506) Asano K … Ogihara T (Human immunology 2007) 3 22 40
  4. Cloning and characterization of an isoform of interleukin-21. (PMID: 17673207) Rahman M … Asao H (FEBS letters 2007) 3 4 22
  5. IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. (PMID: 15178704) Strengell M … Matikainen S (Journal of leukocyte biology 2004) 3 4 22

Products for IL21 Gene

Sources for IL21 Gene