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LIFR (leukemia inhibitory factor receptor alpha)

Written2009-12Nathalie Dagoneau, Valérie Cormier-Daire
Department of Genetics, INSERM U781, Paris Descartes University, Tour Lavoisier, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesleukemia inhibitory factor receptor
Alias_symbol (synonym)CD118
Other aliasFLJ98106
FLJ99923
LIF-R
SJS2
STWS
SWS
HGNC (Hugo) LIFR
LocusID (NCBI) 3977
Atlas_Id 410
Location 5p13.1  [Link to chromosome band 5p13]
Location_base_pair Starts at 38475065 and ends at 38556748 bp from pter ( according to hg19-Feb_2009)  [Mapping LIFR.png]
Fusion genes
(updated 2016)
LIFR (5p13.1) / AKIRIN1 (1p34.3)LIFR (5p13.1) / C9 (5p13.1)LIFR (5p13.1) / PLAG1 (8q12.1)
LIFR (5p13.1) / PNPLA8 (7q31.1)MALAT1 (11q13.1) / LIFR (5p13.1)PLAG1 (8q12.1) / LIFR (5p13.1)

DNA/RNA

 
  SP: signal peptid
CRH1/CRH2: cytokine receptor homology domain
Ig: Ig-like domain
FNIII: type III fibronectin domain
TM: transmembrane domain
CD: cytoplasmic domain
Description At least 20 exons.
Transcription 10258 pb mRNA; 3293 pb open reading frame.

Protein

Description 1097 amino acids; 190 kDa.
Expression Chondrocytes; osteoblasts; skin fibroblasts placenta; brain; mixed; muscle; lung; embryonic tissue; uterus; stomach; kidney; ovary; liver; prostate; vascular; thyroid; testis; eye; pancreas; adrenal gland; spleen; thymus; trachea; larynx; connective tissue; ear; ascites; ganglia; nerve; tonsil; heart; adipose tissue; intestine; mouth (not in lymphocytes).
Localisation Cytoplasmic membrane.
Function LIFR (gp190) and gp130 compose an heterodimeric receptor. The addition of ligand LIF enhances the dimer formation and signal transduction involves the activation of the JAK/STAT and MAPK cascades.
Homology With the IL6 cytokine family receptors.
LIFR depends of the class I cytokine receptor family. The members of this family contain a conserved domain with ~200 amino acid residues in the amino-terminal half and a WSXWS motif in the carboxy-terminal end.

Mutations

Note 14 distinct mutations were identified in 19 families. An identical frameshift insertion (c.653_654insT) was identified in families from the United Arab Emirates, suggesting a founder effect in that region. 12/14 mutations predicted premature termination of translation (Dagoneau et al., 2004; Corona-Rivera et al., 2009).
 

Implicated in

Note
  
Entity Stüve-Wiedemann syndrome
Note SWS / SJS2
Disease Stüve-Wiedemann syndrome is a severe autosomal recessive condition characteried by bowing of the long bones, with cortical thickening, flared metaphyses with coarsened trabecular pattern, camptodactyly, respiratory distress, feeding difficulties, and hyperthermic episodes responsible for early lethality.
  
  
Entity ACTH-secreting pituitary adenomas
Disease LIFR was expressed in all ACTH-secreting adenomas and non functioning adenomas. No LIFR mutations were found (Heutling et al., 2004).
  
  
Entity Pancreatic carcinoma
Disease Pancreatic carcinoma cells expressed LIF, LIFR and gP130 mRNAs. LIF upregulates LIFR mRNA expression and antisense oligonucleotide of LIFR suppresses cell proliferation. The results may be of potential value in immunotherapy for pancreatic carcinoma (Kamohara et al., 2007).
  
  
Entity Neuroblastoma
Disease Growth factors (EGF, FGF) cause a decrease in LIFR levels in neuroblastoma cells that correlated with the activation of extracellular signal-regulated kinase (Erk1/Erk2). The decrease in LIFR is due to an increase in the rate of protein degradation and is blocked by inhibitors of lysosomal degradation (Port et al., 2008).
  
  
Entity Glioblastoma multiforme (GBM)
Disease Glioblastoma multiforme (GBM) represents an extremely chemoresistant tumour type. The authors analysed the expression of selected neural and non-neural differentiation markers including LIFR. They found that LIFR expression was associated with chemosensitivity of tumour cells to several chemotherapeutic agents. However, its role in glioma pathogenesis and response to therapy remains to be elucidated.
  

Bibliography

Flow cytometry analysis of neural differentiation markers expression in human glioblastomas may predict their response to chemotherapy.
Balik V, Mirossay P, Bohus P, Sulla I, Mirossay L, Sarissky M.
Cell Mol Neurobiol. 2009 Sep;29(6-7):845-58. Epub 2009 Mar 14.
PMID 19288188
 
Mutations in the immunoglobulin-like domain of gp190, the leukemia inhibitory factor (LIF) receptor, increase or decrease its affinity for LIF.
Bitard J, Daburon S, Duplomb L, Blanchard F, Vuisio P, Jacques Y, Godard A, Heath JK, Moreau JF, Taupin JL.
J Biol Chem. 2003 May 2;278(18):16253-61. Epub 2003 Feb 24.
PMID 12601009
 
Clinical homogeneity of the Stuve-Wiedemann syndrome and overlap with the Schwartz-Jampel syndrome type 2.
Cormier-Daire V, Superti-Furga A, Munnich A, Lyonnet S, Rustin P, Delezoide AL, De Lonlay P, Giedion A, Maroteaux P, Le Merrer M.
Am J Med Genet. 1998 Jun 30;78(2):146-9.
PMID 9674905
 
Abnormal oral-pharyngeal swallowing as cause of morbidity and early death in Stuve-Wiedemann syndrome.
Corona-Rivera JR, Cormier-Daire V, Dagoneau N, Coello-Ramirez P, Lopez-Marure E, Romo-Huerta CO, Silva-Baez H, Aguirre-Salas LM, Estrada-Solorio MI.
Eur J Med Genet. 2009 Jul-Aug;52(4):242-6. Epub 2009 Apr 14.
PMID 19371797
 
Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome.
Dagoneau N, Scheffer D, Huber C, Al-Gazali LI, Di Rocco M, Godard A, Martinovic J, Raas-Rothschild A, Sigaudy S, Unger S, Nicole S, Fontaine B, Taupin JL, Moreau JF, Superti-Furga A, Le Merrer M, Bonaventure J, Munnich A, Legeai-Mallet L, Cormier-Daire V.
Am J Hum Genet. 2004 Feb;74(2):298-305. Epub 2004 Jan 21.
PMID 14740318
 
The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13.
Gearing DP, Druck T, Huebner K, Overhauser J, Gilbert DJ, Copeland NG, Jenkins NA.
Genomics. 1993 Oct;18(1):148-50.
PMID 8276403
 
Mutation analysis of leukemia inhibitory factor-receptor (LIF-R) in ACTH-secreting pituitary adenomas.
Heutling D, Dieterich KD, Buchfelder M, Lehnert H.
Exp Clin Endocrinol Diabetes. 2004 Sep;112(8):458-61.
PMID 15372367
 
Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression.
Kamohara H, Ogawa M, Ishiko T, Sakamoto K, Baba H.
Int J Oncol. 2007 Apr;30(4):977-83.
PMID 17332938
 
Essential function of LIF receptor in motor neurons.
Li M, Sendtner M, Smith A.
Nature. 1995 Dec 14;378(6558):724-7.
PMID 7501019
 
Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF.
Liu F, Aubin JE, Malaval L.
Bone. 2002 Jul;31(1):212-9.
PMID 12110437
 
The unsolved enigmas of leukemia inhibitory factor.
Metcalf D.
Stem Cells. 2003;21(1):5-14.
PMID 12529546
 
Transregulation of leukemia inhibitory (corrected) factor receptor expression and function by growth factors in neuroblastoma cells.
Port MD, Laszlo GS, Nathanson NM.
J Neurochem. 2008 Aug;106(4):1941-51. Epub 2008 Jul 4.
PMID 18624908
 
Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction.
Starr R, Novak U, Willson TA, Inglese M, Murphy V, Alexander WS, Metcalf D, Nicola NA, Hilton DJ, Ernst M.
J Biol Chem. 1997 Aug 8;272(32):19982-6.
PMID 9242667
 
Congenital bowing of long bones--occurrence in two sisters.
Stuve A, Wiedemann HR.
Z Kinderheilkd. 1971;111(3):184-92.
PMID 5157649
 
Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor.
Tomida M, Gotoh O.
J Biochem. 1996 Jul;120(1):201-5.
PMID 8864865
 
Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death.
Ware CB, Horowitz MC, Renshaw BR, Hunt JS, Liggitt D, Koblar SA, Gliniak BC, McKenna HJ, Papayannopoulou T, Thoma B, et al.
Development. 1995 May;121(5):1283-99.
PMID 7789261
 

Citation

This paper should be referenced as such :
Dagoneau, N ; Cormier-Daire, V
LIFR (leukemia inhibitory factor receptor alpha)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):908-910.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LIFRID410ch5p13.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Head and Neck: Salivary gland tumors: an overview


External links

Nomenclature
HGNC (Hugo)LIFR   6597
Cards
AtlasLIFRID410ch5p13
Entrez_Gene (NCBI)LIFR  3977  leukemia inhibitory factor receptor alpha
AliasesCD118; LIF-R; SJS2; STWS; 
SWS
GeneCards (Weizmann)LIFR
Ensembl hg19 (Hinxton)ENSG00000113594 [Gene_View]  chr5:38475065-38556748 [Contig_View]  LIFR [Vega]
Ensembl hg38 (Hinxton)ENSG00000113594 [Gene_View]  chr5:38475065-38556748 [Contig_View]  LIFR [Vega]
ICGC DataPortalENSG00000113594
TCGA cBioPortalLIFR
AceView (NCBI)LIFR
Genatlas (Paris)LIFR
WikiGenes3977
SOURCE (Princeton)LIFR
Genetics Home Reference (NIH)LIFR
Genomic and cartography
GoldenPath hg19 (UCSC)LIFR  -     chr5:38475065-38556748 -  5p13-p12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)LIFR  -     5p13-p12   [Description]    (hg38-Dec_2013)
EnsemblLIFR - 5p13-p12 [CytoView hg19]  LIFR - 5p13-p12 [CytoView hg38]
Mapping of homologs : NCBILIFR [Mapview hg19]  LIFR [Mapview hg38]
OMIM151443   601559   
Gene and transcription
Genbank (Entrez)AK290059 AK308158 AK309882 BC141428 BC153096
RefSeq transcript (Entrez)NM_001127671 NM_002310
RefSeq genomic (Entrez)NC_000005 NC_018916 NG_011817 NT_006576 NW_004929321
Consensus coding sequences : CCDS (NCBI)LIFR
Cluster EST : UnigeneHs.133421 [ NCBI ]
CGAP (NCI)Hs.133421
Alternative Splicing GalleryENSG00000113594
Gene ExpressionLIFR [ NCBI-GEO ]   LIFR [ EBI - ARRAY_EXPRESS ]   LIFR [ SEEK ]   LIFR [ MEM ]
Gene Expression Viewer (FireBrowse)LIFR [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3977
GTEX Portal (Tissue expression)LIFR
Protein : pattern, domain, 3D structure
UniProt/SwissProtP42702   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP42702  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP42702
Splice isoforms : SwissVarP42702
PhosPhoSitePlusP42702
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)    HEMATOPO_REC_L_F2 (PS01353)   
Domains : Interpro (EBI)FN3_dom    Hematopoietin_rcpt_Gp130_CS    Ig-like_fold   
Domain families : Pfam (Sanger)fn3 (PF00041)   
Domain families : Pfam (NCBI)pfam00041   
Domain families : Smart (EMBL)FN3 (SM00060)  
Conserved Domain (NCBI)LIFR
DMDM Disease mutations3977
Blocks (Seattle)LIFR
PDB (SRS)3E0G   
PDB (PDBSum)3E0G   
PDB (IMB)3E0G   
PDB (RSDB)3E0G   
Structural Biology KnowledgeBase3E0G   
SCOP (Structural Classification of Proteins)3E0G   
CATH (Classification of proteins structures)3E0G   
SuperfamilyP42702
Human Protein AtlasENSG00000113594
Peptide AtlasP42702
HPRD01048
IPIIPI00444272   IPI00967745   IPI00968193   IPI00966270   
Protein Interaction databases
DIP (DOE-UCLA)P42702
IntAct (EBI)P42702
FunCoupENSG00000113594
BioGRIDLIFR
STRING (EMBL)LIFR
ZODIACLIFR
Ontologies - Pathways
QuickGOP42702
Ontology : AmiGOciliary neurotrophic factor receptor activity  leukemia inhibitory factor receptor activity  leukemia inhibitory factor receptor activity  oncostatin-M receptor activity  ciliary neurotrophic factor receptor binding  plasma membrane  integral component of plasma membrane  cell surface receptor signaling pathway  positive regulation of cell proliferation  negative regulation of muscle cell apoptotic process  response to organic cyclic compound  cytokine-mediated signaling pathway  growth factor binding  cytokine binding  organ regeneration  response to cytokine  oncostatin-M-mediated signaling pathway  receptor complex  protein heterodimerization activity  neuron projection morphogenesis  leukemia inhibitory factor signaling pathway  extracellular exosome  ciliary neurotrophic factor-mediated signaling pathway  
Ontology : EGO-EBIciliary neurotrophic factor receptor activity  leukemia inhibitory factor receptor activity  leukemia inhibitory factor receptor activity  oncostatin-M receptor activity  ciliary neurotrophic factor receptor binding  plasma membrane  integral component of plasma membrane  cell surface receptor signaling pathway  positive regulation of cell proliferation  negative regulation of muscle cell apoptotic process  response to organic cyclic compound  cytokine-mediated signaling pathway  growth factor binding  cytokine binding  organ regeneration  response to cytokine  oncostatin-M-mediated signaling pathway  receptor complex  protein heterodimerization activity  neuron projection morphogenesis  leukemia inhibitory factor signaling pathway  extracellular exosome  ciliary neurotrophic factor-mediated signaling pathway  
Pathways : KEGGCytokine-cytokine receptor interaction    Jak-STAT signaling pathway   
REACTOMEP42702 [protein]
REACTOME Pathways6788467 [pathway]   
NDEx NetworkLIFR
Atlas of Cancer Signalling NetworkLIFR
Wikipedia pathwaysLIFR
Orthology - Evolution
OrthoDB3977
GeneTree (enSembl)ENSG00000113594
Phylogenetic Trees/Animal Genes : TreeFamLIFR
HOVERGENP42702
HOGENOMP42702
Homologs : HomoloGeneLIFR
Homology/Alignments : Family Browser (UCSC)LIFR
Gene fusions - Rearrangements
Fusion : MitelmanLIFR/C9 [5p13.1/5p13.1]  
Fusion : MitelmanLIFR/PLAG1 [5p13.1/8q12.1]  [t(5;8)(p13;q12)]  
Fusion : MitelmanLIFR/PNPLA8 [5p13.1/7q31.1]  [t(5;7)(p13;q31)]  
Fusion : COSMICLIFR [5p13.1]  -  PLAG1 [8q12.1]  [fusion_1091]  [fusion_1092]  [fusion_1093]  [fusion_1101]  
Fusion: TCGALIFR 5p13.1 C9 5p13.1 BRCA
Fusion: TCGALIFR 5p13.1 PNPLA8 7q31.1 LGG
Fusion : TICdbLIFR [5p13.1]  -  PLAG1 [8q12.1]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLIFR [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LIFR
dbVarLIFR
ClinVarLIFR
1000_GenomesLIFR 
Exome Variant ServerLIFR
ExAC (Exome Aggregation Consortium)LIFR (select the gene name)
Genetic variants : HAPMAP3977
Genomic Variants (DGV)LIFR [DGVbeta]
DECIPHER (Syndromes)5:38475065-38556748  ENSG00000113594
CONAN: Copy Number AnalysisLIFR 
Mutations
ICGC Data PortalLIFR 
TCGA Data PortalLIFR 
Broad Tumor PortalLIFR
OASIS PortalLIFR [ Somatic mutations - Copy number]
Cancer Gene: CensusLIFR 
Somatic Mutations in Cancer : COSMICLIFR  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDLIFR
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch LIFR
DgiDB (Drug Gene Interaction Database)LIFR
DoCM (Curated mutations)LIFR (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LIFR (select a term)
intoGenLIFR
NCG5 (London)LIFR
Cancer3DLIFR(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM151443    601559   
Orphanet3233   
MedgenLIFR
Genetic Testing Registry LIFR
NextProtP42702 [Medical]
TSGene3977
GENETestsLIFR
Huge Navigator LIFR [HugePedia]
snp3D : Map Gene to Disease3977
BioCentury BCIQLIFR
ClinGenLIFR
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3977
Chemical/Pharm GKB GenePA30371
Clinical trialLIFR
Miscellaneous
canSAR (ICR)LIFR (select the gene name)
Probes
Litterature
PubMed71 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLIFR
EVEXLIFR
GoPubMedLIFR
iHOPLIFR
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:43:35 CET 2017

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