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LIF LIF interleukin 6 family cytokine [ Homo sapiens (human) ]

Gene ID: 3976, updated on 4-Jan-2025

Summary

Official Symbol
LIFprovided by HGNC
Official Full Name
LIF interleukin 6 family cytokineprovided by HGNC
Primary source
HGNC:HGNC:6596
See related
Ensembl:ENSG00000128342 MIM:159540; AllianceGenome:HGNC:6596
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CDF; DIA; HILDA; MLPLI
Summary
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]
Expression
Broad expression in gall bladder (RPKM 20.9), appendix (RPKM 11.6) and 16 other tissues See more
Orthologs
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Genomic context

See LIF in Genome Data Viewer
Location:
22q12.2
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (30240453..30246759, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (30703775..30710077, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (30636442..30642748, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene HORMA domain containing 2 Neighboring gene RPS3A pseudogene 51 Neighboring gene uncharacterized LOC105372988 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18827 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr22:30601719-30602918 Neighboring gene Sharpr-MPRA regulatory region 10236 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:30610529-30611063 Neighboring gene CRISPRi-validated cis-regulatory element chr22.1257 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:30617260-30617890 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30618871-30619372 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30619373-30619872 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:30622687-30623483 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:30624775-30625710 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30627593-30628226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30631328-30631830 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30637625-30638293 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30640698-30641198 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30648163-30648928 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30648929-30649693 Neighboring gene LIF antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13602 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30650183-30650684 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30650685-30651184 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13603 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:30653067-30653669 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:30653670-30654271 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30656529-30657028 Neighboring gene LIF antisense RNA 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30659020-30659819 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30659820-30660618 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18830 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:30672215-30672804 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30673676-30674204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:30674205-30674733 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13605 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13604 Neighboring gene oncostatin M Neighboring gene cytosolic arginine sensor for mTORC1 subunit 1

Genomic regions, transcripts, and products

Expression

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

EBI GWAS Catalog

Description
Common variants at five new loci associated with early-onset inflammatory bowel disease.
EBI GWAS Catalog
Genome-wide association study identifies susceptibility loci for IgA nephropathy.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-treated vaginal epithelial cells show upregulation of leukemia inhibitory factor (LIF) expression as compared to untreated control PubMed
env Pretreatment of MAGI cells with human leukemia inhibitory factor results in a significantly reduced uptake of HIV-1 particles and downregulation of HIV-1 mediated STAT3 phosphorylation PubMed
env HIV-1 gp120 modulates expression of the cytokines IL1beta, IL3, IL6, IL10, IL13, IL15, IFNbeta2A, IFNgamma, IFNomega, TNFalpha, VEGF, VEGF B, and LIF in PBMCs and MDMs PubMed
capsid gag Human LIF protein upregulates HIV-1 p24 production in the chronically infected promonocytes in a dose-dependent manner PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

General gene information

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytokine activity  
enables cytokine activity PubMed 
enables growth factor activity  
enables growth factor activity PubMed 
enables leukemia inhibitory factor receptor binding  
enables leukemia inhibitory factor receptor binding PubMed 
enables leukemia inhibitory factor receptor binding PubMed 
enables protein binding PubMed 
enables signaling receptor binding PubMed 
Items 1 - 25 of 43
Process Evidence Code Pubs
involved_in blood vessel remodeling  
involved_in cell morphogenesis  
involved_in cell surface receptor signaling pathway via STAT PubMed 
involved_in decidualization  
involved_in embryo implantation  
involved_in fibroblast proliferation  
involved_in gene expression  
involved_in immune response  
involved_in leukemia inhibitory factor signaling pathway  
involved_in leukemia inhibitory factor signaling pathway PubMed 
involved_in lung alveolus development  
involved_in lung lobe morphogenesis  
involved_in lung vasculature development  
involved_in macrophage differentiation PubMed 
involved_in meiotic nuclear division  
involved_in muscle organ morphogenesis  
involved_in negative regulation of ERK1 and ERK2 cascade  
involved_in negative regulation of cell population proliferation  
acts_upstream_of_or_within negative regulation of hormone secretion PubMed 
involved_in negative regulation of meiotic nuclear division  
involved_in neuron development  
acts_upstream_of_or_within positive regulation of MAPK cascade PubMed 
involved_in positive regulation of astrocyte differentiation  
involved_in positive regulation of cell adhesion mediated by integrin PubMed 
involved_in positive regulation of cell population proliferation  
acts_upstream_of_or_within positive regulation of cell population proliferation PubMed 
involved_in positive regulation of cell population proliferation PubMed 
involved_in positive regulation of fibroblast proliferation  
involved_in positive regulation of gene expression  
acts_upstream_of_or_within positive regulation of macrophage differentiation PubMed 
involved_in positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis PubMed 
acts_upstream_of_or_within positive regulation of peptidyl-serine phosphorylation PubMed 
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation PubMed 
involved_in positive regulation of receptor signaling pathway via STAT PubMed 
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II PubMed 
involved_in positive regulation of transcription by RNA polymerase II PubMed 
involved_in positive regulation of transcription by RNA polymerase II PubMed 
involved_in regulation of cell differentiation  
involved_in regulation of metanephric nephron tubule epithelial cell differentiation PubMed 
involved_in response to hypoxia  
involved_in somatic stem cell population maintenance  
involved_in stem cell differentiation  
involved_in trophoblast giant cell differentiation  
Items 1 - 25 of 43
Component Evidence Code Pubs
located_in cytosol  
located_in extracellular region  
is_active_in extracellular space  
located_in extracellular space PubMed 

General protein information

Preferred Names
leukemia inhibitory factor
Names
D factor
cholinergic differentiation factor
differentiation inhibitory activity
differentiation-inducing factor
differentiation-stimulating factor
hepatocyte-stimulating factor III
human interleukin in DA cells
melanoma-derived LPL inhibitor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008721.1 RefSeqGene

    Range
    5049..11355
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001257135.2NP_001244064.1  leukemia inhibitory factor isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC004264, AI796373, BC143305, CN409458
    Consensus CDS
    CCDS58799.1
    UniProtKB/Swiss-Prot
    P15018
    Related
    ENSP00000384450.3, ENST00000403987.3
  2. NM_002309.5NP_002300.1  leukemia inhibitory factor isoform 1 precursor

    See identical proteins and their annotated locations for NP_002300.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC004264, AI796373, CN409458
    Consensus CDS
    CCDS13872.1
    UniProtKB/Swiss-Prot
    B2RCW7, B5MC23, P15018, Q52LZ2
    Related
    ENSP00000249075.3, ENST00000249075.4
    Conserved Domains (1) summary
    smart00080
    Location:34191
    LIF_OSM; leukemia inhibitory factor

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    30240453..30246759 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441361.1XP_047297317.1  leukemia inhibitory factor isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    30703775..30710077 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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