Atlas of Genetics and Cytogenetics in Oncology and Haematology

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IL3RA (Interleukin-3 Receptor alpha)

Written2005-05Ugo Testa
Department of Hematology, Oncology, Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy

(Note : for Links provided by Atlas : click)


Other namesCD123
LocusID (NCBI) 3563
Atlas_Id 40959
Location Xp22.33  [Link to chromosome band Xp22]
Location_base_pair Starts at 1455509 and ends at 1501582 bp from pter ( according to and)  [Mapping IL3RA.png]
Fusion genes
(updated 2016)
CSF2RA (Xp22.33) / IL3RA (Xp22.33)


Description The gene encoding interleukin-3 receptor is located in the pseudoautosomal region (PAR) at the end of the short arm of the X and Y chromosomes. The IL-3R alpha chain gene contains twelve exons and eleven introns that span an area of approximately 40 Kb. It is positioned near (190 Kbp) to the gene encoding for GM-CSFR alpha chain. Both the IL-3R alpha and GM-CSFR alpha genes display a similar structural organization, suggesting a common evolutionary origin for both genes.


Description The IL-3R alpha gene encodes a type I transmembrane protein of 41.3 KDa. The IL-3R alpha precursor chain protein is composed by 378 amino acids. Cleavage of the 18 amino acid signal peptide yelds a mature polypeptide chain of 360 amino acids, containing a 288 amino acid extracellular domain involved in IL-3 binding, a 20 amino acid transmembrane domain and a short cytoplasmic tail of 52 amino acids. The extracellular domain is composed by two regions: a N-terminal region of about 100 amino acids, whose sequence exhibits a great similarity to equivalent regions of the GM-CSF and IL-5 receptor alpha-chains; a region, proximal to the transmembrane domain, that contains four conserved cysteine residues and a WSXWS motif, common to other members of this cytokine receptor family. The ligand binding domain consists of about 200 amino acid residue cytokine receptor motifs (CRMs) made up of two Ig-like folding domains. The IL-3R alpha chain is highly glycosylated: six potential N-glycosylation sites have been detected in the extracellular domain. Due to the high glycosylation, the natural IL-3R alpha protein exhibit a MW of about 70 KDa. N-glycosylation is necessary for both ligand binding and receptor signaling. The IL-3R alpha cytoplasmic tail contains a short proline motif, similar to box 1 of the IL-3R beta common chain.
Expression At the level of the hematopoietic system IL-3R alpha expression was described on bone marrow CD34+ cells (including primitive multipotential and committed progenitors), granulocytes, monocytes/macrophages, megakaryocytes and B-lymphocytes. Although the IL-3R alpha is expressed on the large majority of progenitor cells, it does not seem to be expressed on the stem cell fraction. The large majority of CD34+ cells possess IL-3R alpha, but its expression is lost during the initial steps of erythroid differentiation, while its expression is maintained up to terminal stages of granulo-monocytic differentiation. The IL-3R alpha is also a distinctive marker of the "lymphoid" dendritic cells present in peripheral blood. IL-3R alpha expression has also been described in several cell types outside the hemopoeitic system, including endothelial cells, fibroblasts and smooth muscle cells.
Localisation functional mature IL-3R alpha is located at the level of the plasma membrane where it forms a molecular complex with the IL-3R beta chain.
Function IL-3R alpha function can be defined by the activity of its ligand interleukin-3. IL-3 is a multipotent cytokine that promotes the development of hemopoietic progenitors into cells of the erythroid, myeloid and lymphoid lineages. In in vitro colony forming assays IL-3 supports the colony formation by virtually all types of hemopoeitic progenitors, including CFU-GEMM, CFU-GM, CFU-G, CFU-M, CFU-Mk, CFU-E and BFU-E.


Note No mutations of the IL-3Ra gene have been reported in hematological and non hematological human malignancies. Elevated IL-3Ra expression has been reported in about 45% of patients with acute myeloid leukemia and in 40% of patients with acute B lymphoid leukemia. An high IL-3Ra expression has been reported also in hairy cell leukemia.


Analysis of the 5' promoters for human IL-3 and GM-CSF receptor alpha genes.
Akagawa E, Muto A, Arai K, Watanabe S
Biochemical and biophysical research communications. 2003 ; 300 (2) : 600-608.
PMID 12504125
Regulation of myeloid development and function by colony stimulating factors.
Barreda DR, Hanington PC, Belosevic M
Developmental and comparative immunology. 2004 ; 28 (5) : 509-554.
PMID 15062647
Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
Carr PD, Gustin SE, Church AP, Murphy JM, Ford SC, Mann DA, Woltring DM, Walker I, Ollis DL, Young IG
Cell. 2001 ; 104 (2) : 291-300.
PMID 11207369
Identification of primary structural features that define the differential actions of IL-3 and GM-CSF receptors.
Evans CA, Ariffin S, Pierce A, Whetton AD
Blood. 2002 ; 100 (9) : 3164-3174.
PMID 12384414
Site-specific serine phosphorylation of the IL-3 receptor is required for hemopoietic cell survival.
Guthridge MA, Stomski FC, Barry EF, Winnall W, Woodcock JM, McClure BJ, Dottore M, Berndt MC, Lopez AF
Molecular cell. 2000 ; 6 (1) : 99-108.
PMID 10949031
Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.
Itoh N, Yonehara S, Schreurs J, Gorman DM, Maruyama K, Ishii A, Yahara I, Arai K, Miyajima A
Science (New York, N.Y.). 1990 ; 247 (4940) : 324-327.
PMID 2404337
The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells.
Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM, Phillips GL
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (10) : 1777-1784.
PMID 11021753
Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors.
Kitamura T, Sato N, Arai K, Miyajima A
Cell. 1991 ; 66 (6) : 1165-1174.
PMID 1833064
The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling.
Klein BK, Feng Y, McWherter CA, Hood WF, Paik K, McKearn JP
The Journal of biological chemistry. 1997 ; 272 (36) : 22630-22641.
PMID 9278420
Structure of the gene encoding the alpha subunit of the human interleukin 3 receptor.
Kosugi H, Nakagawa Y, Hotta T, Saito H, Miyajima A, Arai K, Yokota T
Biochemical and biophysical research communications. 1995 ; 208 (1) : 360-367.
PMID 7887951
A cytokine receptor gene cluster in the X-Y pseudoautosomal region?
Kremer E, Baker E, D'Andrea RJ, Slim R, Phillips H, Moretti PA, Lopez AF, Petit C, Vadas MA, Sutherland GR
Blood. 1993 ; 82 (1) : 22-28.
PMID 8100720
Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region.
Milatovich A, Kitamura T, Miyajima A, Francke U
American journal of human genetics. 1993 ; 53 (5) : 1146-1153.
PMID 8213838
Expression of interleukin 3 and granulocyte-macrophage colony-stimulating factor receptor common chain betac, betaIT in normal haematopoiesis: lineage specificity and proliferation-independent induction.
Militi S, Riccioni R, Parolini I, Sposi NM, Samoggia P, Pelosi E, Testa U, Peschle C
British journal of haematology. 2000 ; 111 (2) : 441-451.
PMID 11122083
Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies.
Muñoz L, Nomdedéu JF, López O, Carnicer MJ, Bellido M, Aventín A, Brunet S, Sierra J
Haematologica. 2001 ; 86 (12) : 1261-1269.
PMID 11726317
Immunophenotypic features of acute myeloid leukemias overexpressing the interleukin 3 receptor alpha chain.
Riccioni R, Rossini A, Calabrò L, Diverio D, Pasquini L, Lococo F, Peschle C, Testa U
Leukemia & lymphoma. 2004 ; 45 (8) : 1511-1517.
PMID 15370201
Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding.
Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF
Molecular and cellular biology. 1996 ; 16 (6) : 3035-3046.
PMID 8649415
Interleukin-3 receptor in acute leukemia.
Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (2) : 219-226.
PMID 14671644
IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease.
Wong S, McLaughlin J, Cheng D, Shannon K, Robb L, Witte ON
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (20) : 11630-11635.
PMID 14500898


This paper should be referenced as such :
Testa, U
IL3RA (interleukin-3 receptor alpha)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):227-228.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)IL3RA   6012
Entrez_Gene (NCBI)IL3RA  3563  interleukin 3 receptor subunit alpha
AliasesCD123; IL3R; IL3RAY; IL3RX; 
IL3RY; hIL-3Ra
GeneCards (Weizmann)IL3RA
Ensembl hg19 (Hinxton)ENSG00000185291 [Gene_View]  chrX:1455509-1501582 [Contig_View]  IL3RA [Vega]
Ensembl hg38 (Hinxton)ENSG00000185291 [Gene_View]  chrX:1455509-1501582 [Contig_View]  IL3RA [Vega]
ICGC DataPortalENSG00000185291
TCGA cBioPortalIL3RA
Genatlas (Paris)IL3RA
SOURCE (Princeton)IL3RA
Genetics Home Reference (NIH)IL3RA
Genomic and cartography
GoldenPath hg19 (UCSC)IL3RA  -     chrX:1455509-1501582 +  Xp22.3   [Description]    (and)
GoldenPath hg38 (UCSC)IL3RA  -     Xp22.3   [Description]    (hg38-Dec_2013)
EnsemblIL3RA - Xp22.3 [CytoView hg19]  IL3RA - Xp22.3 [CytoView hg38]
Mapping of homologs : NCBIIL3RA [Mapview hg19]  IL3RA [Mapview hg38]
OMIM308385   430000   
Gene and transcription
Genbank (Entrez)AI765858 AK290568 AW452270 BC035407 EU176623
RefSeq transcript (Entrez)NM_001267713 NM_002183
RefSeq genomic (Entrez)NC_000023 NC_000024 NC_018934 NT_167201 NT_187358 NW_004929437
Consensus coding sequences : CCDS (NCBI)IL3RA
Cluster EST : UnigeneHs.632790 [ NCBI ]
CGAP (NCI)Hs.632790
Alternative Splicing GalleryENSG00000185291
Gene ExpressionIL3RA [ NCBI-GEO ]   IL3RA [ EBI - ARRAY_EXPRESS ]   IL3RA [ SEEK ]   IL3RA [ MEM ]
Gene Expression Viewer (FireBrowse)IL3RA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3563
GTEX Portal (Tissue expression)IL3RA
Protein : pattern, domain, 3D structure
UniProt/SwissProtP26951 (Uniprot)
NextProtP26951  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP26951
Splice isoforms : SwissVarP26951 (Swissvar)
Domaine pattern : Prosite (Expaxy)HEMATOPO_REC_S_F2 (PS01356)   
Domains : Interpro (EBI)FN3_dom    Ig-like_fold    Short_hematopoietin_rcpt_2_CS    TypeI_recpt_CBD   
Domain families : Pfam (Sanger)IL6Ra-bind (PF09240)   
Domain families : Pfam (NCBI)pfam09240   
DMDM Disease mutations3563
Blocks (Seattle)IL3RA
Structural Biology KnowledgeBase4JZJ   
SCOP (Structural Classification of Proteins)4JZJ   
CATH (Classification of proteins structures)4JZJ   
Human Protein AtlasENSG00000185291
Peptide AtlasP26951
IPIIPI00003058   IPI00553194   
Protein Interaction databases
IntAct (EBI)P26951
Ontologies - Pathways
Ontology : AmiGOMAPK cascade  protein tyrosine kinase activity  interleukin-3 receptor activity  Ras guanyl-nucleotide exchange factor activity  intracellular  plasma membrane  integral component of membrane  peptidyl-tyrosine phosphorylation  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  positive regulation of GTPase activity  
Ontology : EGO-EBIMAPK cascade  protein tyrosine kinase activity  interleukin-3 receptor activity  Ras guanyl-nucleotide exchange factor activity  intracellular  plasma membrane  integral component of membrane  peptidyl-tyrosine phosphorylation  cellular response to interleukin-3  interleukin-3-mediated signaling pathway  positive regulation of GTPase activity  
Pathways : BIOCARTARegulation of BAD phosphorylation [Genes]    IL 3 signaling pathway [Genes]   
Pathways : KEGGCytokine-cytokine receptor interaction    PI3K-Akt signaling pathway    Apoptosis    Jak-STAT signaling pathway    Hematopoietic cell lineage   
REACTOMEP26951 [protein]
REACTOME PathwaysR-HSA-912526 Interleukin receptor SHC signaling [pathway]
REACTOME PathwaysR-HSA-392451 G beta:gamma signalling through PI3Kgamma [pathway]
REACTOME PathwaysR-HSA-5673001 RAF/MAP kinase cascade [pathway]
REACTOME PathwaysR-HSA-912526 Interleukin receptor SHC signaling [pathway]
REACTOME PathwaysR-HSA-114604 GPVI-mediated activation cascade [pathway]
REACTOME PathwaysR-HSA-512988 Interleukin-3, 5 and GM-CSF signaling [pathway]
NDEx NetworkIL3RA
Atlas of Cancer Signalling NetworkIL3RA
Wikipedia pathwaysIL3RA
Orthology - Evolution
GeneTree (enSembl)ENSG00000185291
Phylogenetic Trees/Animal Genes : TreeFamIL3RA
Homologs : HomoloGeneIL3RA
Homology/Alignments : Family Browser (UCSC)IL3RA
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerIL3RA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)IL3RA
Exome Variant ServerIL3RA
ExAC (Exome Aggregation Consortium)IL3RA (select the gene name)
Genetic variants : HAPMAP3563
Genomic Variants (DGV)IL3RA [DGVbeta]
DECIPHER (Syndromes)X:1455509-1501582  ENSG00000185291
CONAN: Copy Number AnalysisIL3RA 
ICGC Data PortalIL3RA 
TCGA Data PortalIL3RA 
Broad Tumor PortalIL3RA
OASIS PortalIL3RA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICIL3RA 
Mutations and Diseases : HGMDIL3RA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch IL3RA
DgiDB (Drug Gene Interaction Database)IL3RA
DoCM (Curated mutations)IL3RA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)IL3RA (select a term)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM308385    430000   
Genetic Testing Registry IL3RA
NextProtP26951 [Medical]
Huge Navigator IL3RA [HugePedia]
snp3D : Map Gene to Disease3563
BioCentury BCIQIL3RA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3563
Chemical/Pharm GKB GenePA29831
Clinical trialIL3RA
canSAR (ICR)IL3RA (select the gene name)
PubMed69 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Oct 10 11:31:04 CEST 2016

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