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FLASH GENE
Symbol IL21 contributors: mct - updated : 10-04-2019
HGNC name interleukin 21
HGNC id 6005
Corresponding disease
CVID11 common variable immunodeficiency 11
Location 4q27      Physical location : 123.533.782 - 123.542.211
Synonym name interleukin-21 isoform
Synonym symbol(s) IL-21, Za11
DNA
TYPE functioning gene
STRUCTURE 8.43 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure
  • a REL binding site identified in the proximal promoter of IL21 is confirmed to bind REL and to regulate expression from the IL21 promoter in T cells )
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC391691 4 similar to ARHGAP20 protein MAD2L1 4q27 MAD2 mitotic arrest deficient-like 1 (yeast) LOC344988 4q27 similar to GTP-binding protein SAR1a (COPII-associated small GTPase) PRDM5 4q27 PR domain containing 5 FLJ23191 4q27 hypothetical protein FLJ23191 TNIP3 4q27 TNFAIP3 interacting protein 3 GPR103 4q27 G protein-coupled receptor 103 LOC391692 4 similar to TUBULIN BETA CHAIN ANXA5 4q26-q27 annexin A5 FLJ30834 4q27 hypothetical protein FLJ30834 PMSCL1 4q27 polymyositis/scleroderma autoantigen 1, 75kDa CCNA2 4q27 cyclin A2 BBS7 4q27 Bardet-Biedl syndrome 7 TRPC3 4q25-q27 transient receptor potential cation channel, subfamily C, member 3 KIAA1109 4q28.1 hypothetical protein KIAA1109 Tenr 4q28.1 testis nuclear RNA-binding protein IL2 4q26-q27 interleukin 2 IL21 4q26-q27 interleukin 21 FLJ35630 4q28.1 hypothetical protein FLJ35630 FGF2 4q26 fibroblast growth factor 2 (basic) NUDT6 4q26 nudix (nucleoside diphosphate linked moiety X)-type motif 6 SPATA5 4q27 spermatogenesis associated 5 SPRY1 4q26-q27 sprouty homolog 1, antagonist of FGF signaling (Drosophila) LOC391693 4 similar to ribosomal protein L21 LOC391694 4 similar to Peptidylprolyl isomerase A (cyclophilin A) LOC391695 4 similar to Tubulin alpha-4 chain (Alpha-tubulin 4) LOC391696 4 similar to Synaptic glycoprotein SC2 KIAA1223 4q28.1 KIAA1223 protein LOC339951 4q28.1 similar to ENSANGP00000007226
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 616 - 162 - 2010 20817119
    4 - 707 - 153 - 2010 20817119
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunenatural killer Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • IL-15/IL-21 family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text
  • IL21 is mainly produced from activated CD4+ T cells and natural killer T (NKT) cells
  • basic FUNCTION
  • involved in the cross-talk between epithelial and immune cells in the gut
  • has pleiotropic actions, from augmenting the proliferation of T cells and driving the differentiation of B cells into memory cells and terminally differentiated plasma cells to augmenting the activity of natural killer cells
  • serves as a critical helper factor that is required for viral control in CD8+ T cells
  • acts directly on B cells and cooperates with TLR signaling for optimal B cell responses
  • plays a critical role in the expansion and differentiation of the Th cell subsets, Th17 and follicular helper T (T(FH)) cells
  • IL21 and CD40LG collaborate through at least two distinct mechanisms to synergistically promote PRDM1 activation and plasma cells (PCs) differentiation
  • IL21 and CSF2 exhibit cross-regulatory actions on gene regulation and apoptosis, regulating conventional dendritic cells (cDCs) numbers and thereby the magnitude of the immune response
  • IL21 suppresses the development of Th2 cells and functions of polarized Th2 cells
  • critical role of IL21 in breaking immune homeostasis in aplastic anemia (AA) by promoting Th17 cells, activating BM T cells and suppressing Tregs
  • is a type I cytokine essential for immune cell differentiation and function
  • IL21 exerts major effects on B-cell activation and differentiation or apoptosis during humoral immune responses and induces differentiation of na
  • ve B cells and memory B cells into plasma cells
  • IL21 modulates the effector functions of T, B and NK cells, which not only have key roles in antitumoral and antiviral immunity but also in exerting major effects on inflammatory responses promoting the development of autoimmune diseases
  • context-dependent role for IL21 in sustaining effector phenotype CD8 T cells and influencing their migratory properties, accumulation, and functions
  • IL21 may link immune responses to physiological or pathological platelet-dependent processes
  • regulates megakaryocyte development and platelet homeostasis
  • IL21 reinforces humoral immunity by restricting T follicular regulatory (Tfr) cell proliferation
  • is crucial for the development of a robust CD8+ T cell response and has been shown to promote antitumor immunity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • IL21/IL21R pathway is a critical component of the memory B cell response
  • IL21 signaling has an intrinsic role in promoting the protective capacity of T cells
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • link between IL21-induced JAK/STAT signaling, MYC regulation, and differentiation of human B cells
  • IL21 drives CD8(+) CTL differentiation via the actions of the transcription factor TBX21
  • role for IL21 as an inducer of the costimulatory ligand CD86 on B lymphocytes
  • IL21 is an inducer of IL22 production in CD4+ T cells
  • STAT1 and STAT3 have at least partially opposing roles in IL21 signaling in CD4(+) T cells
  • interplay between STAT1 and STAT3 in fine-tuning IL21 actions
  • IL6 is a master regulator of IL21 in effector CD8+ T cells
  • is produced predominantly by activated CD4+ T cells and has pleiotropic effects on immunity via IL21R
  • IL4 and IL21 cooperate to induce the high BCL6 protein level required for germinal center formation
  • PTPN11 is involved in the IL21-mediated ERK1/2 activation and cell proliferation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CVID11
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    IL21 and IL21R expression in lymphocytes and neurons in multiple sclerosis brain
    tumoral     --low  
    in osteosarcoma patients
    Susceptibility to systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP
  • both IL21 rs907715 and rs2221903 polymorphisms may be associated with SLE susceptibility
  • Candidate gene
    Marker
  • IL21 is a candidate biomarker of resistance to tuberculosis
  • Therapy target
    ANIMAL & CELL MODELS