Atlas of Genetics and Cytogenetics in Oncology and Haematology


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CRLF2 (Cytokine receptor like factor 2)

Written2019-02Dafné Moreno-Lorenzana, RocÍo Juárez-Velázquez, Daniel MartÍnez-Anaya, Patricia Péez-Vera
Laboratorio de Genética y Cáncer. Instituto Nacional de PediatrÍa (DML, RJV, DMA, PPV); Cátedra CONACYT-Instituto Nacional de PediatrÍa (DML); Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (DMA). / e-Mail pperezvera@yahoo.com

Abstract CRLF2 is a member of type I cytokine receptor family. CRLF2 forms a functional complex with IL-7 receptor α chain and thymic stromal lymphopoietin, this complex induces the activation of signal transducers and activators of transcription proteins. The overexpression of CRLF2 induced by genetic rearrangements has been described in acute lymphoblastic leukemia.

Keywords CRLF2; Cytokine receptor; TSLP; Jak-Stat pathway.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)CRL2
TSLPR
Other alias
HGNC (Hugo) CRLF2
Atlas_Id 51262
Location Xp22.33 and Yp11.2, negative strand. ENSG00000205755  [Link to chromosome band Xp22]
Location_base_pair Starts at 1190496 and ends at 1212723 bp from pter ( according to and)  [Mapping CRLF2.png]
Local_order CRLF2 is located on chromosome X and Y, on the short arm and lies between RPL14P5 (ribosomal protein L4 pseudogene 5) and CSF2RA (colony stimulating factor 2 receptor alpha subunit). Entrez Gene ID: 64109
 
  A) Chromosomal location of CRLF2 gene. B) Mapping of CRLF2 gene and local order on genomic context of the chromosome X and Y.
 
  Chromosomes obtained from MHH-CALL-4 cell line positive to IGH/CRLF2 translocation detected by fluorescence in situ hybridization (FISH). The der(Y) chromosome is lost in the cell line. Metaphase hybridized with CRLF2 break-apart probe (Cytocell Aquarius) with a normal chromosome X (green-red signal, yellow arrow), and der(14) (green signal, white arrow).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
IGH/CRLF2P2RY8/CRLF2CSF2RA/CRLF2
CHRFAM7A/CRLF2CRLF2/U2AF1GOLGA8A/CRLF2
WDR27/CRLF2

DNA/RNA

 
  CRLF2 gene encodes four transcript variants: two with 8 exons, one with 9 exons, and one with 7 exons (exons are represented by violet boxes and introns by black line). ENSG00000205755, Entrez Gene ID: 64109
Description CRLF2 gene is located in reverse strand of pseudo-autosomal region 1 (PAR1) in X and Y chromosomes. CRLF2 encompasses 22kb of DNA and give rise to four transcript variants with different lengths: 1.6, 1.5, 1.0 and 1.7 kb. ENSG00000205755
Transcription CRLF2 gene encodes a member of type I cytokine receptor family and generate four transcript variants (Table 1). Three generate protein coding transcripts and one generates a non-sense mediated decay transcript.
According with gene expression array data CRLF2 is expressed, from highest to lowest, in: cervix > lung > bladder > small intestine > esophagus > stomach > skin > prostate > uterus > vagina > testes > colon > spleen > mammary gland > thyroid > whole blood.
It has been reported that in pathological conditions the transcription rate of CRLF2 is altered. CRLF2 overexpression (fold change > 2) is found in: microbial infection, immunodeficiency syndromes (X-linked hyper IgM syndrome), autoimmune diseases (arthritis), and cancer (esophagus dysplasia, papillary thyroid carcinoma and acute lymphoblastic leukemia). The CRLF2 subexpression (fold change < 2) has been reported only in cancer (myelodysplastic syndrome, non-small cell lung carcinoma, hepatobiliary carcinoma, colorectal carcinoma, pancreatic adenocarcinoma and breast carcinoma). ENSG00000205755; UniProt Q9HC73; neXtProt NX_Q9HC73
Table 1. Transcript variants and proteins
Name (RefSeq)Exons  Coding Exons  Transcript Length  Protein Length  Type of transcript
CRLF2-203 (NM_022148)   88 1, 639 bp371 residuesProtein coding
CRLF2-201 9  8 1, 545 bp371 residuesProtein coding
CRLF2-202 (NM_001012288)  76 1, 013 bp259 residuesProtein coding
CRLF2-204 (NR_110830)  85 1, 789 bp232 residuesNon-sense mediated decay

Protein

 
  Isoform 1 is a single-pass type I membrane protein, have a length of 371 aa. Protein sequence includes four main regions: FN3 (Fibronectin type 3), encompassed from 109 to 207 aa; WSXWS motif, encompassed from 200 to 204 aa; Box 1 motif encompassed from 261 to 269 aa; Transmembrane region encompassed from 232 to 252 aa.
Isoform 2 is a secreted protein an only have FN3 region, encompassed from 7 to 76 aa.
Description CRLF2 gene encodes a member of the type I cytokine receptor family. CRLF2 has three protein coding transcripts: CRLF2-201, CRLF2-202, CRLF2-203 and CRLF2-204.
CRLF2-203 and CRLF2-201 transcript variants generate the longer isoform of 371 amino acids (42 kDa), also called isoform 1.
Isoform 1 has the protein regions that characterize this family gene: FN3 (Fibronectin type 3) region, WSXWS motif, Box 1 motif, and transmembrane region. Post-translational modifications of CRLF2 protein include glycosylation at asparagine residues (Asn169, Asn55 and Asn47) and phosphorylation at isoleucine (Ile271) and tyrosine (Tyr74) residues.
The other isoform, called isoform 2, is encoded by the transcript variant CRLF2-202. This isoform is shorter, 259 amino acids (26.6 kDa), at N-terminus compared with isoform 1 because lacks an alternate exon which results in translation initiation at a downstream start codon. ENSG00000205755; UniProt Q9HC73, Q9HC73-2, Q4V300; neXtProt NX_Q9HC73
Expression CRLF2 protein is present in intestine, bone marrow, spleen, thymus, and is more abundant in dendritic cells. neXtProt NX_Q9HC73
Localisation CRLF2 isoform 1 is a cell membrane protein and CRLF2 isoform 2 is a secreted protein.
 
  A) TSLP /CRLF2/ IL7R complex activation is implicated in Th2 differentiation. TSLP binds to CRLF2/IL-7Rα heterodimer in dendritic cells and promotes the expression of OX40 ligand ( TNFSF4 (CD252)) and IL13, IL5, IL4 and TNF to induce Th2 differentiation. B) TSLP/CRLF2/IL-7Rα complex activation in dendritic cells. Activation of CRLF2 was described by first time in dendritic cells. This scheme exemplifies the main nodes involved.
Function CRLF2 forms a functional complex with IL-7Rα (IL-7 receptor α chain) and TSLP (thymic stromal lymphopoietin). Functional complex activation induces different signals depending on the type of cell and also exerts multiple functions. Heterocomplex is involved in a plethora of physiologic and pathologic immune functions, including: tolerance, allergy, autoimmune diseases and cancer. (Tsilingin et al., 2017).
CRLF2 is expressed mainly in dendritic cells and also hematopoietic cells including T cells, B cells, granulocytes, and mast cells. Heterocomplex main function is the differentiation to T helper type 2 (Th2) cells. CRLF2-activated dendritic cells express OX40 ligand and trigger naive CD4+ to differentiate into inflammatory Th2 cells and the expansion of allergen-specific Th2 memory cells (Lin et al., 2018).
According with phosphoproteome analysis in diverse cell types, after TSLP binds to the CRLF2/IL-7Rα heterocomplex, the phosphorylation of Janus kinase1 ( JAK1) and 2 ( JAK2) activates signal transducers and activators of transcription (STATs) proteins, including: STAT1, STAT3, STAT4, STAT5A, STAT5B and STAT6. Heterocomplex also activates other signaling molecules such as PI3K/AKT/MTOR pathway, SRC / TEC pathway, MAPK3 / MAPK1 (ERK1/2), NF-kB, MAPK8 / MAPK9 (JNK1 JNK2), and p38/MAPK activation (Zhong Jun et al., 2012; Zhong Jun et al., 2014).
In allergy or autoimmune disease has been described high expression of TSLP and overstimulation of TSLP/CRLF2/IL-7Rα complex. Tezepelumab is a human monoclonal antibody that blocks functional complex and is successfully used in asthma treatment (Van Rompaey et al., 2012).
The role of functional heterocomplex in cancer is still controversial, in certain neoplasia plays a pro-tumorigenic role, whereas in others, a protective role. For example, in cervix, breast, and pancreas cancer has been describe an increase of metastasis associated with an overstimulation of TSLP/CRLF2/IL-7Rα. On the other hand, in colon and skin carcinoma, functional heterocomplex has been associated with better prognostic. In addition to above, CRLF2 gene has genetic alterations that promote cell survival in cancer. The genetic rearrangements P2RY8/CRLF2 and IGH/CRLF2, generate CRLF2 overexpression, and the mutation Phe232Cys, encodes CRLF2 proteins capable of forming homodimers and self-activation, both described in acute lymphoblastic leukemia (Varricchi et al., 2018; Zhong Jun, 2014).
 
  C) Phosphoproteomic analysis reveals multiple targets in TSLP/CRLF2/IL-7Rα pathway in different cell types. This scheme shows experimental curated data obtained from NetSlim.
Homology Table 2. CRLF2 Orthologues
NameOrganism
CRLF2 P. troglodytes
CRLF2 (ENSCAFG00000011034)  C. lupus
LOC529792 (ENSBTAG00000020242)  B. taurus
Crlf2 (ENSMUSG00000033467)  M. musculus
Crlf2 (ENSRNOG00000049828)  R. novergicus
LOC418668 (ENSGALG00000016696)  G. gallus

Mutations

 
  Mutations in CRLF2 have been identified in a wide range of cancer types. Most of them are missense mutations (green), nonsense mutations are also represented (violet).
Somatic Table 3 CRLF2 mutations in cancer
CDS Mutation  Cancer TypeType of Mutation
c.315C>A Bladder CarcinomaMissense mutation
c.357C>ABladder CarcinomaMissense mutation
c.193G>ABladder CarcinomaMissense mutation
c.89T>ABladder CarcinomaMissense mutation
c.33C>GDiffuse Large B Cell LymphomaMissense mutation
c.415T>CDiffuse Large B Cell LymphomaMissense mutation
c.349C>TOsteosarcomaMissense mutation
c.330T>CColon CarcinomaMissense mutation
c.384G>AColon CarcinomaMissense mutation
c.33C>GColon CarcinomaMissense mutation
c.159G>ARectum CarcinomaMissense mutation
c.474C>TAdenocarcinomaMissense mutation
c.372C>TAdenocarcinomaMissense mutation
c.411G>AAdenocarcinomaMissense mutation
c.603C>TAdenocarcinomaMissense mutation
c.405G>AAdenocarcinomaMissense mutation
c.669G>AAdenocarcinomaMissense mutation
c.642T>CAdenocarcinomaMissense mutation
c.642T>CEndometrioid CarcinomaMissense mutation
c.321C>TLung CarcinomaMissense mutation
c.384G>APleura CarcinomaMissense mutation
c.456C>TMelanomaMissense mutation
c.411G>AMelanomaMissense mutation
c.468C>TMelanomaMissense mutation
c.123C>TMelanomaMissense mutation
c.630G>AMelanomaMissense mutation
c.534G>AMelanomaMissense mutation
c.438C>TMelanomaMissense mutation
c.383C>TMerkel Cell CarcinomaMissense mutation
c-.335G>TMerkel Cell CarcinomaMissense mutation
c.604G>AUrinary Tract CarcinomaMissense mutation
c.742C>AUrinary Tract CarcinomaMissense mutation
c.208C>ANeuroblastomaMissense mutation
c.139A>TGliomaMissense mutation
c.404C>TGliomaMissense mutation
c.365C>TGliomaMissense mutation
c.598C>AGliomaMissense mutation
c.404C>TGliomaMissense mutation
c.313C>TGliomaMissense mutation
c.74G>AGliomaMissense mutation
c.632G>AGliomaMissense mutation
c.445G>AMeningiomaMissense mutation
c.660G>TBreast CarcinomaMissense mutation
c.734C>TBreast CarcinomaMissense mutation
c.526G>CBreast CarcinomaMissense mutation
c.297C>GCervix CarcinomaMissense mutation
c.658G>CCervix CarcinomaMissense mutation
c.566C>TEndometrium CarcinomaMissense mutation
c.536A>TEndometrium CarcinomaMissense mutation
c.643C>TEndometrium CarcinomaMissense mutation
c.7C>TEndometrium CarcinomaMissense mutation
c.496A>CEndometrium CarcinomaMissense mutation
c.373G>AEndometrium CarcinomaMissense mutation
c.346T>CEndometrium CarcinomaMissense mutation
c.495A>CEndometrium CarcinomaMissense mutation
c.248G>TKidney CarcinomaMissense mutation
c.526G>ALiver CarcinomaMissense mutation
c.105C>GLiver CarcinomaMissense mutation
c.671C>TAcute Myeloid LeukemiaMissense mutation
c.695T>GB Cell Acute Lymphoblastic Leukemia  Missense mutation
c.2T>AMantle Cell LymphomaMissense mutation
c.340G>CMarginal Zone LymphomaMissense mutation
c.228C>THead and Neck CarcinomaMissense mutation
c.764G>AMelanomaNo sense mutation
c.764G>AMelanomaNo sense mutation
c.755G>AHead and Neck CarcinomaNo sense mutation
c.755G>AMelanomaNo sense mutation
c.451C>TMelanomaNo sense mutation
c.628C>TPancreasNo sense mutation
c.137G>AColon CarcinomaNo sense mutation
c.620C>GIntestinal AdenocarcinomaNo sense mutation
c.91C>TGlioblastoma MultiformeNo sense mutation
c.73G>TAdenocarcinomaNo sense mutation
c.54G>AHead and Neck CarcinomaNo sense mutation
c.25G>TLung CarcinomaNo sense mutation

Catalogue of Somatic Mutations in Cancer; cBioPortal for Cancer Genomics

Implicated in

  
Entity Hematological malignancies
Oncogenesis The t(X;14)(p22;q32) or t(Y;14)(p11;q32) rearrange CRLF2 with immunoglobulin heavy chain gene forming IGH/CRLF2 rearrangement. With P2Y purinoceptor 8 gene ( P2RY8), located also in the pseudoautosomal (PAR1) region of X or Y chromosomes, CRLF2 forms a rearrangement through the interstitial deletions del(X)(p22p22) or del(Y)(p11p11). Both abnormalities are associated with B-precursor acute lymphoblastic leukemia (pre-B ALL) and Down syndrome pre-B ALL (Entrez Gene ID: 64109; Russell LJ et al., 2009).
It has been referred similar deletions in the PAR1 region involving the interleukin 3 receptor subunit alpha ( IL3RA) gene or the colony stimulating factor 2 receptor alpha subunit (CSF2RA) gene and CRLF2, indicating that the breakpoints are variable between patients. Interestingly, one patient has been reported with the CSF2RA/CRLF2 rearrangement and IGH/ EPOR (Yano M et al., 2015). These rearrangements produce the overexpression of CRLF2 by the juxtaposition of this gene within the gene promoter of P2RY8, AKAP17A (SFRS17A), or ASMT (Russell LJ et al., 2009). Biallelic deletions of the PAR1 region, including CSF2RA and CRLF2 genes, have been reported in mantle cell lymphoma (Nieländer I et al., 2008).
In addition, four fusions with CRLF2 have been also reported: 1) CHRFAM7A /CRLF2 with the cholinergic receptor, nicotinic, alpha 7, exons 5-10 and he family with sequence similarity 7A, exons A-E fusion gene (CHRNA7) located in 15q13 (Fusion gen ID: 7161); 2) CRLF2/ U2AF1 with the U2 small nuclear RNA auxiliary factor 1 gene (U2F1), associated with myelodysplastic syndrome, and located in 21q22.3 (Fusion gen ID: 8499); 3) GOLGA8A /CRLF2 with the golgin A8 family member A gene (GOLGA8A) in 15q14 (Fusion gen ID: 15056); 4) WDR27 /CRLF2 with the WD repeat domain 27 gene (WDR27) in 6q27 (Fusion gen ID: 41824).
  
  
Entity Pulmonary alveolar proteinosis
Note A recessive pattern of another similar homozygous deletion, that disrupts CSF2RA, CRLF2, and IL3RA gene, was found in a boy with pulmonary alveolar proteinosis, an accumulation of surfactant in the alveoli. Surfactant is cleared by alveolar macrophages, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and its signaling is necessary for this process. GM-CSF activates Jak-Stat pathway inducing phagocytic functions of alveolar macrophage and catabolize surfactant (Chiu CY et al., 2017).
  

Bibliography

Whole-Genome Sequencing of a Family with Hereditary Pulmonary Alveolar Proteinosis Identifies a Rare Structural Variant Involving CSF2RA/CRLF2/IL3RA Gene Disruption
Chiu CY, Su SC, Fan WL, Lai SH, Tsai MH, Chen SH, Wong KS, Chung WH.
Gene Disruption,2017; 7: 43469.
PMID 28233860
 
Expression and regulation of thymic stromal lymphopoietin and thymic stromal lymphopoietin receptor heterocomplex in the innate-adaptive immunity of pediatric asthma
Lin SC, Cheng FY, Liu JJ, Ye YL
Int J Mol Sci. 2018; 19(4)
PMID 29670037
 
Recurrent loss of the Y chromosome and homozygous deletions within the pseudoautosomal region 1: association with male predominance in mantle cell lymphoma
Nieländer I, MartÍn-Subero JI, Wagner F, Baudis M, Gesk S, Harder L, Hasenclever D, Klapper W, Kreuz M, Pott C, Martinez-Climent JA, Dreyling M, Arnold N, Siebert R
Haematologica. 2008;93(6):949-50
PMID 18515880
 
Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia
Russell LJ, Capasso M, Vater I, Akasaka T, Bernard OA, Calasanz MJ, Chandrasekaran T, Chapiro E, Gesk S, Griffiths M, Guttery DS, Haferlach C, Harder L, Heidenreich O, Irving J, Kearney L, Nguyen-Khac F, Machado L, Minto L, Majid A, Moorman AV, Morrison H, Rand V, Strefford JC, Schwab C, Tönnies H, Dyer MJ, Siebert R, Harrison CJ
Blood. 2009;114(13):2688-98
PMID 19641190
 
Thymic Stromal Lymphopoietin: to cut a long story short
Tsilingiri K, Fornasa G, Rescigno M
Cell Mol Gastroenterol Hepatol. 2017; 3(2):174-182
PMID 28275684
 
Virtual screening for inhibitors of the human TSLP: TSLPR interaction
Van Rompaey D, Verstraete K, Peelman F, Savvides SN, Augustyns K, Van Der Veken P, De Winter H
Sci Rep. 2017; 1: 17211
PMID 29222519
 
Thymic stromal lymphopoietin isoforms, inflammatory disorders and cancer
Varricchi G, Pecoraro A, Marone G, Criscuolo G, Spadaro G, Genovese A, Marone G
Front Immunol. 2018; 9: 1595
PMID 30057581
 
Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion
Yano M, Imamura T, Asai D, Kiyokawa N, Nakabayashi K, Matsumoto K, Deguchi T, Hashii Y, Honda YK, Hasegawa D, Sasahara Y, Ishii M, Kosaka Y, Kato K, Shima M, Hori H, Yumura-Yagi K, Hara J, Oda M, Horibe K, Ichikawa H, Sato A
Br J Haematol. 2015;171(5):813-7
PMID 18515880
 
TSLP signaling network revealed by SILAC-based phosphoproteomics
Zhong J, Kim MS, Chaerkady R, Wu X, Huang TC, Getnet D, Mitchell CJ, Palapetta SM, Sharma J, O'Meally RN, Cole RN, Yoda A, Moritz A, Loriaux MM, Rush J, Weinstock DM, Tyner JW, Pandey A
Mol Cell Proteomics. 2012;11(6):M112.017764
PMID 22345495
 
TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling
Zhong J, Sharma J, Raju R, Palapetta SM, Prasad TS, Huang TC, Yoda A, Tyner JW, van Bodegom D, Weinstock DM, Ziegler SF, Pandey A
Database (Oxford).2014:bau007.
PMID 24573880
 

Citation

This paper should be referenced as such :
Moreno-Lorenzana D ,2, Juárez-Velázquez R, MartÍnez-Anaya D,3, Péez Vera P
CRLF2 (Cytokine receptor like factor 2);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/CRLF2ID51262chXp22.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 5 ]
  del(X)(p22p22) P2RY8/CRLF2::del(Y)(p11p11) P2RY8/CRLF2
Acute lymphoblastic leukemia in Down syndrome
t(X;14)(p22;q32) or t(Y;14)(p11;q32) IGH/CRLF2
del(X)(p22p22) CSF2RA/CRLF2
t(X;14)(p22;q32) IGH/CRLF2


External links

Nomenclature
HGNC (Hugo)CRLF2   14281
Cards
AtlasCRLF2ID51262chXp22
Entrez_Gene (NCBI)CRLF2  64109  cytokine receptor like factor 2
AliasesCRL2; CRLF2Y; TSLPR
GeneCards (Weizmann)CRLF2
Ensembl hg19 (Hinxton)ENSG00000205755 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000205755 [Gene_View]  ENSG00000205755 [Sequence]  chrX:1190496-1212723 [Contig_View]  CRLF2 [Vega]
ICGC DataPortalENSG00000205755
TCGA cBioPortalCRLF2
AceView (NCBI)CRLF2
Genatlas (Paris)CRLF2
WikiGenes64109
SOURCE (Princeton)CRLF2
Genetics Home Reference (NIH)CRLF2
Genomic and cartography
GoldenPath hg38 (UCSC)CRLF2  -     chrX:1190496-1212723 -  Xp22.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CRLF2  -     Xp22.33   [Description]    (hg19-Feb_2009)
GoldenPathCRLF2 - Xp22.33 [CytoView hg19]  CRLF2 - Xp22.33 [CytoView hg38]
ImmunoBaseENSG00000205755
Mapping of homologs : NCBICRLF2 [Mapview hg19]  CRLF2 [Mapview hg38]
OMIM300357   400023   
Gene and transcription
Genbank (Entrez)AB052639 AF142570 AF338733 AK026800 AK223303
RefSeq transcript (Entrez)NM_001012288 NM_022148
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CRLF2
Cluster EST : UnigeneHs.287729 [ NCBI ]
CGAP (NCI)Hs.287729
Alternative Splicing GalleryENSG00000205755
Gene ExpressionCRLF2 [ NCBI-GEO ]   CRLF2 [ EBI - ARRAY_EXPRESS ]   CRLF2 [ SEEK ]   CRLF2 [ MEM ]
Gene Expression Viewer (FireBrowse)CRLF2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
GTEX Portal (Tissue expression)CRLF2
Human Protein AtlasENSG00000205755-CRLF2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9HC73   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9HC73  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9HC73
Splice isoforms : SwissVarQ9HC73
PhosPhoSitePlusQ9HC73
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)   
Domains : Interpro (EBI)FN3_dom    FN3_sf    Ig-like_fold   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CRLF2
DMDM Disease mutations64109
Blocks (Seattle)CRLF2
PDB (RSDB)5J11    5J12   
PDB Europe5J11    5J12   
PDB (PDBSum)5J11    5J12   
PDB (IMB)5J11    5J12   
Structural Biology KnowledgeBase5J11    5J12   
SCOP (Structural Classification of Proteins)5J11    5J12   
CATH (Classification of proteins structures)5J11    5J12   
SuperfamilyQ9HC73
Human Protein Atlas [tissue]ENSG00000205755-CRLF2 [tissue]
Peptide AtlasQ9HC73
HPRD02288
IPIIPI00030172   IPI00385014   IPI00553195   
Protein Interaction databases
DIP (DOE-UCLA)Q9HC73
IntAct (EBI)Q9HC73
FunCoupENSG00000205755
BioGRIDCRLF2
STRING (EMBL)CRLF2
ZODIACCRLF2
Ontologies - Pathways
QuickGOQ9HC73
Ontology : AmiGOcytokine receptor activity  cytokine receptor activity  cytokine receptor activity  extracellular region  plasma membrane  positive regulation of cell proliferation  positive regulation of cell proliferation  external side of plasma membrane  integral component of membrane  cytokine-mediated signaling pathway  cytokine binding  positive regulation of mast cell activation  interleukin-7-mediated signaling pathway  receptor complex  positive regulation of STAT cascade  positive regulation of interleukin-5 secretion  
Ontology : EGO-EBIcytokine receptor activity  cytokine receptor activity  cytokine receptor activity  extracellular region  plasma membrane  positive regulation of cell proliferation  positive regulation of cell proliferation  external side of plasma membrane  integral component of membrane  cytokine-mediated signaling pathway  cytokine binding  positive regulation of mast cell activation  interleukin-7-mediated signaling pathway  receptor complex  positive regulation of STAT cascade  positive regulation of interleukin-5 secretion  
Pathways : KEGGCytokine-cytokine receptor interaction    Jak-STAT signaling pathway   
REACTOMEQ9HC73 [protein]
REACTOME PathwaysR-HSA-1266695 [pathway]   
NDEx NetworkCRLF2
Atlas of Cancer Signalling NetworkCRLF2
Wikipedia pathwaysCRLF2
Orthology - Evolution
GeneTree (enSembl)ENSG00000205755
Phylogenetic Trees/Animal Genes : TreeFamCRLF2
HOGENOMQ9HC73
Homologs : HomoloGeneCRLF2
Homology/Alignments : Family Browser (UCSC)CRLF2
Gene fusions - Rearrangements
Fusion : MitelmanCSF2RA/CRLF2 [Xp22.33/Xp22.33]  [del(X)(p22p22)]  
Fusion : MitelmanIGH/CRLF2 [14q32.33/Xp22.33]  [t(X;14)(p22;q32)]  [t(Y;14)(p11;q32)]  
Fusion : MitelmanP2RY8/CRLF2 [Xp22.33/Xp22.33]  [del(X)(p22p22)]  
Fusion : TICdbP2RY8 [Xp22.33]  -  CRLF2 [Xp22.33]
Fusion : FusionGDB15056    41824    7161    8499   
Fusion : Fusion_HubAGAP8--CRLF2    ANAPC16--CRLF2    ARL10--CRLF2    BCL10--CRLF2    CHRFAM7A--CRLF2    CRLF2--CSF2RA    CRLF2--CTSS    CRLF2--ELMOD1    CRLF2--IDS    CRLF2--IGH@    CRLF2--IGHD    CRLF2--IGHM    CRLF2--LYZ    CRLF2--METTL7A    CRLF2--P2RY8   
CRLF2--PMS2CL    CRLF2--SIK2    CRLF2--TADA2A    CRLF2--U2AF1    CSF2RA--CRLF2    GOLGA8A--CRLF2    IGH--CRLF2    P2RY8--CRLF2    WDR27--CRLF2   
Fusion : QuiverCRLF2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCRLF2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CRLF2
dbVarCRLF2
ClinVarCRLF2
1000_GenomesCRLF2 
Exome Variant ServerCRLF2
ExAC (Exome Aggregation Consortium)ENSG00000205755
GNOMAD BrowserENSG00000205755
Varsome BrowserCRLF2
Genetic variants : HAPMAP64109
Genomic Variants (DGV)CRLF2 [DGVbeta]
DECIPHERCRLF2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCRLF2 
Mutations
ICGC Data PortalCRLF2 
TCGA Data PortalCRLF2 
Broad Tumor PortalCRLF2
OASIS PortalCRLF2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCRLF2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCRLF2
BioMutasearch CRLF2
DgiDB (Drug Gene Interaction Database)CRLF2
DoCM (Curated mutations)CRLF2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CRLF2 (select a term)
intoGenCRLF2
NCG5 (London)CRLF2
Cancer3DCRLF2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM300357    400023   
Orphanet
DisGeNETCRLF2
MedgenCRLF2
Genetic Testing Registry CRLF2
NextProtQ9HC73 [Medical]
GENETestsCRLF2
Target ValidationCRLF2
Huge Navigator CRLF2 [HugePedia]
snp3D : Map Gene to Disease
BioCentury BCIQCRLF2
ClinGenCRLF2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD64109
Chemical/Pharm GKB GenePA26883
Clinical trialCRLF2
Miscellaneous
canSAR (ICR)CRLF2 (select the gene name)
DataMed IndexCRLF2
Probes
Litterature
PubMed61 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCRLF2
EVEXCRLF2
GoPubMedCRLF2
iHOPCRLF2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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