The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the mate... See more...

Aliases for LIF Gene

Aliases for LIF Gene

  • LIF Interleukin 6 Family Cytokine 2 3 5
  • Leukemia Inhibitory Factor 2 3 4
  • Differentiation Inhibitory Activity 2 3
  • Differentiation-Stimulating Factor 3 4
  • Cholinergic Differentiation Factor 2 3
  • Hepatocyte-Stimulating Factor III 2 3
  • Differentiation-Inducing Factor 2 3
  • Melanoma-Derived LPL Inhibitor 3 4
  • Human Interleukin In DA Cells 2 3
  • D Factor 3 4
  • HILDA 3 4
  • MLPLI 3 4
  • LIF, Interleukin 6 Family Cytokine 2
  • Emfilermin 4
  • CDF 3
  • DIA 3

External Ids for LIF Gene

Previous GeneCards Identifiers for LIF Gene

  • GC22M027332
  • GC22M028960
  • GC22M030636
  • GC22M013598

Summaries for LIF Gene

Entrez Gene Summary for LIF Gene

  • The protein encoded by this gene is a pleiotropic cytokine with roles in several different systems. It is involved in the induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, regulator of mesenchymal to epithelial conversion during kidney development, and may also have a role in immune tolerance at the maternal-fetal interface. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneCards Summary for LIF Gene

LIF (LIF Interleukin 6 Family Cytokine) is a Protein Coding gene. Diseases associated with LIF include Leukemia and Ectopic Pregnancy. Among its related pathways are Cytokine Signaling in Immune system and ERK Signaling. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and growth factor activity.

UniProtKB/Swiss-Prot Summary for LIF Gene

  • LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.

Gene Wiki entry for LIF Gene

Additional gene information for LIF Gene

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

Genomics for LIF Gene

GeneHancer (GH) Regulatory Elements for LIF Gene

Promoters and enhancers for LIF 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
GH22J030234 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 762.3 +11.2 11209 24.6 ZNF785 SIN3A CTCF POLR2A USF2 NR2F1 NR2F6 ZNF362 CC2D1A ZNF701 ENSG00000268812 LIF SF3A1 RNF215 TUG1 TBC1D10A EWSR1 PES1 MORC2 ASCC2
GH22J030259 Promoter 0.5 Ensembl 756.7 -1.8 -1778 0.6 ZNF121 PRDM10 LIF OSM
GH22J030415 Promoter/Enhancer 2.6 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 23.9 -163.5 -163509 11.7 ZNF785 ZNF24 SP1 CTCF SREBF1 SIX5 FOXA1 MLX RBPJ SMARCE1 RNF215 ENSG00000272689 ENSG00000273350 MTFP1 RF00026-674 RNU6-564P TUG1 SF3A1 ASCC2 TBC1D10A
GH22J029305 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 15.8 +948.8 948789 7.7 CTCF RBPJ SMARCE1 ZNF362 MYC ELF1 L3MBTL2 RAD21 ZNF121 POLR2A GAS2L1 ENSG00000268812 ENSG00000272858 LIF ASCC2 CHEK2 XBP1 RASL10A AP1B1 RHBDD3
GH22J030287 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 16 -32.2 -32235 5 ZNF785 SIN3A SP1 CTCF ZBTB6 MLX RBPJ TCF7L2 CC2D1A NFYC CASTOR1 lnc-CASTOR1-1 RNF215 ENSG00000268812 LIF TBC1D10A ASCC2 TUG1 CCDC157 SF3A1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LIF on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the LIF gene promoter:
  • ATF-2
  • c-Jun
  • c-Myc
  • Max
  • STAT1
  • STAT1beta
  • STAT3
  • STAT5A

Genomic Locations for LIF Gene

Genomic Locations for LIF Gene
chr22:30,240,447-30,257,923
(GRCh38/hg38)
Size:
17,477 bases
Orientation:
Minus strand
chr22:30,636,436-30,642,840
(GRCh37/hg19)
Size:
6,405 bases
Orientation:
Minus strand

Genomic View for LIF Gene

Genes around LIF on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for LIF Gene

Proteins for LIF Gene

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

    Protein Symbol:
    P15018-LIF_HUMAN
    Recommended name:
    Leukemia inhibitory factor
    Protein Accession:
    P15018
    Secondary Accessions:
    • B2RCW7
    • B5MC23
    • Q52LZ2

    Protein attributes for LIF Gene

    Size:
    202 amino acids
    Molecular mass:
    22008 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for LIF Gene

    Alternative splice isoforms for LIF Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LIF Gene

Post-translational modifications for LIF Gene

  • Glycosylation at Asn31, Asn56, Asn85, Asn95, Asn118, and Asn138

Other Protein References for LIF Gene

Antibody Products

  • Abcam antibodies for LIF
  • Santa Cruz Biotechnology (SCBT) Antibodies for LIF

Protein Products

  • Abcam proteins for LIF

No data available for DME Specific Peptides for LIF Gene

Domains & Families for LIF Gene

Gene Families for LIF Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for LIF Gene

GenScript: Design optimal peptide antigens:
  • Melanoma-derived LPL inhibitor (LIF_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P15018

UniProtKB/Swiss-Prot:

LIF_HUMAN :
  • Belongs to the LIF/OSM family.
Family:
  • Belongs to the LIF/OSM family.
genes like me logo Genes that share domains with LIF: view

Function for LIF Gene

Molecular function for LIF Gene

UniProtKB/Swiss-Prot Function:
LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.
GENATLAS Biochemistry:
leukemia inhibitory factor (differentiation-stimulating factor),interleukin-6 cytokine family member stimulating hematopoiesis,platelet production,localized distally to the breakpoint in t(11;22)(q24;q12)

LifeMap Function Summary for LIF Gene

LIF as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for LIF Gene

Gene Ontology (GO) - Molecular Function for LIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IPI 8999038
GO:0005125 cytokine activity IDA 7957045
GO:0005146 leukemia inhibitory factor receptor binding IPI 8999038
GO:0005515 protein binding IPI 14527405
GO:0008083 growth factor activity IDA 7957045
genes like me logo Genes that share ontologies with LIF: view
genes like me logo Genes that share phenotypes with LIF: view

Animal Models for LIF Gene

MGI Knock Outs for LIF:
  • Lif Lif<tm1Stw>
  • Lif Lif<tm1Phb>
  • Lif Lif<tm1Cgre>

Animal Model Products

CRISPR Products

Clone Products

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

Localization for LIF Gene

Subcellular locations from UniProtKB/Swiss-Prot for LIF Gene

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 LIF gene
Compartment Confidence
extracellular 5
cytosol 5
plasma membrane 2
cytoskeleton 2
nucleus 2
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for LIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA,IC 12643274
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with LIF: view

Pathways & Interactions for LIF Gene

PathCards logo

SuperPathways for LIF Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.47
.46
2 ERK Signaling
.61
.61
.51
3 Akt Signaling
.60
.60
4 PAK Pathway
.56
.56
5 NFAT and Cardiac Hypertrophy
.42
.42
genes like me logo Genes that share pathways with LIF: view

SIGNOR curated interactions for LIF Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for LIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001974 blood vessel remodeling IEA --
GO:0006955 immune response IEA --
GO:0007260 tyrosine phosphorylation of STAT protein IEA --
GO:0007275 multicellular organism development TAS 3143918
GO:0007566 embryo implantation IEA --
genes like me logo Genes that share ontologies with LIF: view

Drugs & Compounds for LIF Gene

(56) Drugs for LIF Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(51) Additional Compounds for LIF Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with LIF: view

Transcripts for LIF Gene

mRNA/cDNA for LIF Gene

(2) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(47) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

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

No ASD Table

Relevant External Links for LIF Gene

GeneLoc Exon Structure for
LIF
ECgene alternative splicing isoforms for
LIF

Expression for LIF Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LIF Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x4.6) and Prostate (x4.4).

Protein differential expression in normal tissues from HIPED for LIF Gene

This gene is overexpressed in Cerebrospinal fluid (57.7) and Bone marrow mesenchymal stem cell (8.4).

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



Protein tissue co-expression partners for LIF Gene

NURSA nuclear receptor signaling pathways regulating expression of LIF Gene:

LIF

SOURCE GeneReport for Unigene cluster for LIF Gene:

Hs.2250

Evidence on tissue expression from TISSUES for LIF Gene

  • Intestine(4.2)
  • Nervous system(2.6)
  • Muscle(2.2)
  • Blood(2.1)
  • Bone marrow(2)
  • Heart(2)
  • Skin(2)
genes like me logo Genes that share expression patterns with LIF: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for LIF Gene

Orthologs for LIF Gene

This gene was present in the common ancestor of chordates.

Orthologs for LIF Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LIF 33 32
  • 99.83 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LIF 33 32
  • 91.91 (n)
OneToOne
cow
(Bos Taurus)
Mammalia LIF 33 32
  • 88.61 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Lif 32
  • 82.34 (n)
mouse
(Mus musculus)
Mammalia Lif 17 33 32
  • 81.19 (n)
oppossum
(Monodelphis domestica)
Mammalia LIF 33
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LIF 33
  • 60 (a)
OneToOne
chicken
(Gallus gallus)
Aves LIF 33 32
  • 59.83 (n)
OneToOne
Species where no ortholog for LIF was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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 LIF Gene

ENSEMBL:
Gene Tree for LIF (if available)
TreeFam:
Gene Tree for LIF (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LIF: view image

Paralogs for LIF Gene

No data available for Paralogs for LIF Gene

Variants for LIF Gene

Sequence variations from dbSNP and Humsavar for LIF Gene

SNP ID Clin Chr 22 pos Variation AA Info Type
rs41281637 benign, not specified 30,244,004(-) C/T coding_sequence_variant, missense_variant
rs1000049734 -- 30,259,309(-) G/A/T upstream_transcript_variant
rs1000148623 -- 30,246,739(-) C/A/T 5_prime_UTR_variant
rs1000161723 -- 30,241,832(-) T/A 3_prime_UTR_variant
rs1000222709 -- 30,255,652(-) T/C genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for LIF Gene

Variant ID Type Subtype PubMed ID
esv995861 CNV gain 20482838
nsv1110864 OTHER inversion 24896259
nsv829171 CNV loss 20364138
nsv834173 CNV loss 17160897
nsv834174 CNV gain+loss 17160897

Variation tolerance for LIF Gene

Residual Variation Intolerance Score: 44.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.59; 44.93% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LIF Gene

Human Gene Mutation Database (HGMD)
LIF
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LIF

SNP Genotyping and Copy Number Assay Products

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

Disorders for LIF Gene

MalaCards: The human disease database

(17) MalaCards diseases for LIF Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
leukemia
  • leukemias
ectopic pregnancy
  • eccyesis
complement deficiency
  • complement deficiency disease
null-cell leukemia
  • null cell acute lymphoblastic leukemia
cerebral meningioma
  • meningioma of cerebrum
- elite association - COSMIC cancer census association via MalaCards
Search LIF in MalaCards View complete list of genes associated with diseases

Additional Disease Information for LIF

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with LIF: view

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

Publications for LIF Gene

  1. An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor. (PMID: 17652170) Huyton T … Garrett TP (Proceedings of the National Academy of Sciences of the United States of America 2007) 3 4 23 56
  2. Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women. (PMID: 18298054) Králícková M … Vetvicka V (Folia microbiologica 2007) 3 23 43 56
  3. Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130. (PMID: 14527405) Boulanger MJ … Garcia KC (Molecular cell 2003) 3 4 23 56
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 43 56
  5. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 43 56

Products for LIF Gene

Sources for LIF Gene