This gene encodes a member of the type I cytokine receptor family. The encoded protein is a receptor for thymic stromal lymphopoietin (TSLP). Together with the interleukin 7 receptor (IL7R), the encoded protein and TSLP activate STAT3, STAT5, and JAK2 pathways, which control processes such as cell proliferation and development of the hematopoietic system. Rearrangement of this ... See more...

Aliases for CRLF2 Gene

Aliases for CRLF2 Gene

  • Cytokine Receptor Like Factor 2 2 3 5
  • TSLPR 2 3 4
  • CRL2 2 3 4
  • Thymic Stromal Lymphopoietin Protein Receptor 3 4
  • Cytokine Receptor-Like Factor 2 3 4
  • TSLP Receptor 3 4
  • IL-XR 3 4
  • Thymic Stromal-Derived Lymphopoietin Receptor 3
  • Cytokine Receptor CRL2 Precusor 3
  • Cytokine Receptor-Like 2 4
  • CRLF2Y 3
  • CRLF2 5
  • ILXR 4

External Ids for CRLF2 Gene

Previous GeneCards Identifiers for CRLF2 Gene

  • GC00U990849
  • GC0YU900015
  • GC0XM9W0034
  • GC0XP9W0020
  • GC0XM001274

Summaries for CRLF2 Gene

Entrez Gene Summary for CRLF2 Gene

  • This gene encodes a member of the type I cytokine receptor family. The encoded protein is a receptor for thymic stromal lymphopoietin (TSLP). Together with the interleukin 7 receptor (IL7R), the encoded protein and TSLP activate STAT3, STAT5, and JAK2 pathways, which control processes such as cell proliferation and development of the hematopoietic system. Rearrangement of this gene with immunoglobulin heavy chain gene (IGH) on chromosome 14, or with P2Y purinoceptor 8 gene (P2RY8) on the same X or Y chromosomes is associated with B-progenitor acute lymphoblastic leukemia (ALL) and Down syndrome ALL. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

CIViC Summary for CRLF2 Gene

GeneCards Summary for CRLF2 Gene

CRLF2 (Cytokine Receptor Like Factor 2) is a Protein Coding gene. Diseases associated with CRLF2 include Lymphoblastic Leukemia, Acute, With Lymphomatous Features and Leukemia, Acute Lymphoblastic. Among its related pathways are Innate Lymphoid Cell Differentiation Pathways and PEDF Induced Signaling. An important paralog of this gene is IL6ST.

UniProtKB/Swiss-Prot Summary for CRLF2 Gene

  • Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2 (By similarity). Implicated in the development of the hematopoietic system.

Gene Wiki entry for CRLF2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CRLF2 Gene

Genomics for CRLF2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CRLF2 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
GH0XJ001212 Promoter 0.5 Ensembl 250.7 +0.5 461 0.2 POLR2A DPF2 CRLF2 piR-38580-393 RF00017-7492 RF00017-7488 MN298114-298 RF00017-7486 RF00017-7475 SHOX
GH0XJ001247 Promoter/Enhancer 0.9 FANTOM5 CraniofacialAtlas 4.1 -35.9 -35866 0.5 TCF7L2 TAF1 ZNF652 SIN3A PRDM10 POLR2A KDM1A CSF2RA IL3RA ASMTL AKAP17A CRLF2 ASMT SLC25A6 P2RY8 RF00017-7495 LOC107985697
GH0XJ001500 Enhancer 1.3 FANTOM5 Ensembl dbSUPER 2.4 -292.7 -292738 9.8 BCLAF1 SP1 ZNF207 NCOR1 MYC ZNF592 POLR2A NFIC BCL11A CTCF RF00017-7504 P2RY8 AKAP17A CSF2RA IL3RA ASMTL ASMT CRLF2 SLC25A6 RF00017-7486
GH0XJ001239 Enhancer 0.8 FANTOM5 3.7 -27.1 -27084 0.3 BCLAF1 SP1 BCL11A IRF4 EBF1 CBFB SMARCA5 BHLHE40 SPI1 BATF LOC107985697 CSF2RA IL3RA ASMTL AKAP17A CRLF2 ASMT SLC25A6 P2RY8 piR-53431-693
GH0XJ001215 Enhancer 0.8 FANTOM5 Ensembl 3.3 -2.2 -2239 2.8 BCL11A FOXA2 EBF1 CBFB BHLHE40 SPI1 POLR2A IKZF1 MTA3 ZNF217 IL3RA CSF2RA AKAP17A ASMTL CRLF2 ASMT SLC25A6 P2RY8 hsa-miR-5096-169 RF00017-7492
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CRLF2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CRLF2

Genomic Locations for CRLF2 Gene

Latest Assembly
chrX:1,190,437-1,212,762
(GRCh38/hg38)
Size:
22,326 bases
Orientation:
Minus strand

Previous Assembly
chrX:1,314,869-1,331,542
(GRCh37/hg19 by Entrez Gene)
Size:
16,674 bases
Orientation:
Minus strand

chrX:1,314,890-1,331,616
(GRCh37/hg19 by Ensembl)
Size:
16,727 bases
Orientation:
Minus strand

Alternative Locations (GRCh38/hg38)

  • chrY:1,190,437-1,212,762 (-)

Genomic View for CRLF2 Gene

Genes around CRLF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CRLF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CRLF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRLF2 Gene

Proteins for CRLF2 Gene

  • Protein details for CRLF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HC73-CRLF2_HUMAN
    Recommended name:
    Cytokine receptor-like factor 2
    Protein Accession:
    Q9HC73
    Secondary Accessions:
    • J3QKD1
    • Q5G7M1
    • Q9H5R3

    Protein attributes for CRLF2 Gene

    Size:
    371 amino acids
    Molecular mass:
    42013 Da
    Quaternary structure:
    • Heterodimer of CRLF2 and IL7R.
    Miscellaneous:
    • The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.

    Three dimensional structures from OCA and Proteopedia for CRLF2 Gene

    Alternative splice isoforms for CRLF2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CRLF2 Gene

Post-translational modifications for CRLF2 Gene

  • Glycosylation at Asn47, Asn55, Asn169, and Asn101
  • Modification sites at PhosphoSitePlus

Antibodies for research

  • Abcam antibodies for CRLF2

Assay products for research

  • Abcam assays for CRLF2

No data available for DME Specific Peptides for CRLF2 Gene

Domains & Families for CRLF2 Gene

Gene Families for CRLF2 Gene

Protein Domains for CRLF2 Gene

Suggested Antigen Peptide Sequences for CRLF2 Gene

GenScript: Design optimal peptide antigens:
  • Thymic stromal lymphopoietin protein receptor (CRLF2_HUMAN)
  • Thymic stromal-derived lymphopoietin receptor transcript variant 2 (Q5G7M1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HC73

UniProtKB/Swiss-Prot:

CRLF2_HUMAN :
  • The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
  • Belongs to the type I cytokine receptor family. Type 5 subfamily.
Domain:
  • The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
  • The box 1 motif is important for association with JAKs.
Family:
  • Belongs to the type I cytokine receptor family. Type 5 subfamily.
genes like me logo Genes that share domains with CRLF2: view

Function for CRLF2 Gene

Molecular function for CRLF2 Gene

UniProtKB/Swiss-Prot Function:
Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2 (By similarity). Implicated in the development of the hematopoietic system.
UniProtKB/Swiss-Prot Induction:
Up-regulated in activated peripheral monocytes and THP-1 cells.

Phenotypes From GWAS Catalog for CRLF2 Gene

Gene Ontology (GO) - Molecular Function for CRLF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004896 cytokine receptor activity IMP 17242164
GO:0004923 leukemia inhibitory factor receptor activity IBA 21873635
GO:0004924 contributes_to oncostatin-M receptor activity IBA 21873635
GO:0005127 ciliary neurotrophic factor receptor binding IBA 21873635
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with CRLF2: view
genes like me logo Genes that share phenotypes with CRLF2: view

Animal Models for CRLF2 Gene

MGI Knock Outs for CRLF2:

Animal Models for research

  • Taconic Biosciences Mouse Models for CRLF2

miRNA for CRLF2 Gene

miRTarBase miRNAs that target CRLF2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CRLF2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CRLF2 Gene

Localization for CRLF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CRLF2 Gene

[Isoform 1]: Cell membrane. Single-pass type I membrane protein.
[Isoform 2]: 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 CRLF2 gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 2
golgi apparatus 2
cytoskeleton 1
mitochondrion 1
endosome 1
cytosol 1
lysosome 1
peroxisome 0
endoplasmic reticulum 0

Gene Ontology (GO) - Cellular Components for CRLF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0009897 external side of plasma membrane IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with CRLF2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CRLF2 Gene

Pathways & Interactions for CRLF2 Gene

genes like me logo Genes that share pathways with CRLF2: view

Pathways by source for CRLF2 Gene

SIGNOR curated interactions for CRLF2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CRLF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008284 positive regulation of cell proliferation IBA,IDA 11418668
GO:0019221 cytokine-mediated signaling pathway IDA 11418668
GO:0032754 positive regulation of interleukin-5 production IMP 17242164
GO:0033005 positive regulation of mast cell activation IMP 17242164
GO:0038111 interleukin-7-mediated signaling pathway TAS --
genes like me logo Genes that share ontologies with CRLF2: view

Drugs & Compounds for CRLF2 Gene

(1) Drugs for CRLF2 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
N/A Pharma inhibitor 0
genes like me logo Genes that share compounds with CRLF2: view

Transcripts for CRLF2 Gene

mRNA/cDNA for CRLF2 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
4 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 CRLF2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for CRLF2 Gene

No ASD Table

Relevant External Links for CRLF2 Gene

GeneLoc Exon Structure for
CRLF2

Expression for CRLF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CRLF2 Gene

Protein differential expression in normal tissues from HIPED for CRLF2 Gene

This gene is overexpressed in Tlymphocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CRLF2 Gene



Protein tissue co-expression partners for CRLF2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CRLF2

SOURCE GeneReport for Unigene cluster for CRLF2 Gene:

Hs.287729

mRNA Expression by UniProt/SwissProt for CRLF2 Gene:

Q9HC73-CRLF2_HUMAN
Tissue specificity: Expressed in heart, skeletal muscle, kidney and adult and fetal liver. Primarily expressed in dendrites and monocytes. Weakly expressed in T-cells.

Evidence on tissue expression from TISSUES for CRLF2 Gene

  • Blood(4.4)
  • Spleen(4.4)
  • Lymph node(4.4)
  • Lung(4.4)
genes like me logo Genes that share expression patterns with CRLF2: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CRLF2 Gene

Orthologs for CRLF2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CRLF2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CRLF2 29
  • 98.76 (n)
Dog
(Canis familiaris)
Mammalia CRLF2 29 30
  • 71.32 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LOC529792 29
  • 67.86 (n)
CRLF2 30
  • 37 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Crlf2 29 16 30
  • 50.1 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Crlf2 29
  • 49.23 (n)
Oppossum
(Monodelphis domestica)
Mammalia CRLF2 30
  • 39 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CRLF2 30
  • 28 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LOC418668 29
  • 49.11 (n)
CRLF2 30
  • 25 (a)
OneToOne
Species where no ortholog for CRLF2 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)
  • 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 CRLF2 Gene

ENSEMBL:
Gene Tree for CRLF2 (if available)
TreeFam:
Gene Tree for CRLF2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CRLF2: view image
Alliance of Genome Resources:
Additional Orthologs for CRLF2

Paralogs for CRLF2 Gene

(2) SIMAP similar genes for CRLF2 Gene using alignment to 3 proteins:

  • CRLF2_HUMAN
  • J3QKD1_HUMAN
  • Q4V300_HUMAN
genes like me logo Genes that share paralogs with CRLF2: view

Variants for CRLF2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CRLF2 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
rs1057519743 Pathogenic: Lymphoblastic leukemia, acute, with lymphomatous features 1,196,852(-) A/C
NM_022148.4(CRLF2):c.695T>G (p.Phe232Cys)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs138899368 Not Provided: not specified 1,202,479(-) C/T
NM_022148.4(CRLF2):c.406G>A (p.Val136Met)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs151218732 Not Provided: not specified 1,196,817(-) C/T
NM_022148.4(CRLF2):c.730G>A (p.Val244Met)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs200254974 Not Provided: not specified 1,198,571(-) C/T
NM_022148.4(CRLF2):c.637G>A (p.Glu213Lys)
MISSENSE
rs587778218 Not Provided: not specified 1,206,513(-) T/C
NM_022148.4(CRLF2):c.269A>G (p.Gln90Arg)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CRLF2 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 CRLF2 Gene

Variant ID Type Subtype PubMed ID
esv21933 CNV gain+loss 19812545
esv2739631 CNV deletion 23290073
esv2739633 CNV deletion 23290073
esv2739634 CNV deletion 23290073
esv29996 CNV loss 17803354
esv3558469 CNV deletion 23714750
nsv1077569 CNV duplication 25765185
nsv1115919 CNV duplication 24896259
nsv1126938 CNV deletion 24896259
nsv1126959 CNV deletion 24896259
nsv953389 CNV deletion 24416366

Variation tolerance for CRLF2 Gene

Gene Damage Index Score: 1.93; 35.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CRLF2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CRLF2
Leiden Open Variation Database (LOVD)
CRLF2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CRLF2 Gene

Disorders for CRLF2 Gene

MalaCards: The human disease database

(15) MalaCards diseases for CRLF2 Gene - From: CVR, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search CRLF2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CRLF2

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 CRLF2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CRLF2 Gene

Publications for CRLF2 Gene

  1. Identification of a novel type I cytokine receptor CRL2 preferentially expressed by human dendritic cells and activated monocytes. (PMID: 11237741) Zhang W … Cao X (Biochemical and biophysical research communications 2001) 2 3 4 22
  2. Molecular cloning of a human novel type I cytokine receptor related to delta1/TSLPR. (PMID: 11474172) Tonozuka Y … Kitamura T (Cytogenetics and cell genetics 2001) 2 3 4 22
  3. Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. (PMID: 19965641) Hertzberg L … Izraeli S (Blood 2010) 3 22 72
  4. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. (PMID: 22368272) Chen IM … Willman CL (Blood 2012) 3 72
  5. Thymic stromal lymphopoietin-induced human asthmatic airway epithelial cell proliferation through an IL-13-dependent pathway. (PMID: 20236697) Semlali A … Chakir J (The Journal of allergy and clinical immunology 2010) 3 22

Products for CRLF2 Gene

Sources for CRLF2 Gene