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

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
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: mouse all
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Genomic context

Location:: 22q12.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	22	NC_000022.11 (30240453..30257487, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (30636442..30642748, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis.
Title: The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis.
Plasma proteomics identifies leukemia inhibitory factor (LIF) as a novel predictive biomarker of immune-checkpoint blockade resistance.
Title: Plasma proteomics identifies leukemia inhibitory factor (LIF) as a novel predictive biomarker of immune-checkpoint blockade resistance.
Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers.
Title: Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers.
Autocrine Leukemia Inhibitory Factor Promotes Esophageal Squamous Cell Carcinoma Progression via Src Family Kinase-Dependent Yes-Associated Protein Activation.
Title: Autocrine Leukemia Inhibitory Factor Promotes Esophageal Squamous Cell Carcinoma Progression via Src Family Kinase-Dependent Yes-Associated Protein Activation.
Leukemia inhibitory factor: A main controller of breast cancer.
Title: Leukemia inhibitory factor: A main controller of breast cancer.
LIF in embryo culture medium is a predictive marker for clinical pregnancy following IVF-ET of patients with fallopian tube obstruction.
Title: LIF in embryo culture medium is a predictive marker for clinical pregnancy following IVF-ET of patients with fallopian tube obstruction.
Association of novel stop-gained leukaemia inhibitory factor receptor gene (rs121912501) variant, leukaemia inhibitory factor and ovarian steroids with unexplained infertility among Pakistani women.
Title: Association of novel stop-gained leukaemia inhibitory factor receptor gene (rs121912501) variant, leukaemia inhibitory factor and ovarian steroids with unexplained infertility among Pakistani women.
Polymorphism in the 3'-UTR of LIF but Not in the ATF6B Gene Associates with Schizophrenia Susceptibility: a Case-Control Study and In Silico Analyses.
Title: Polymorphism in the 3'-UTR of LIF but Not in the ATF6B Gene Associates with Schizophrenia Susceptibility: a Case-Control Study and In Silico Analyses.
Leukemia inhibitory factor is a novel biomarker to predict lymph node and distant metastasis in pancreatic cancer.
Title: Leukemia inhibitory factor is a novel biomarker to predict lymph node and distant metastasis in pancreatic cancer.
Induced Pluripotent Stem Cell-Derived Conditioned Medium Promotes Endogenous Leukemia Inhibitory Factor to Attenuate Endotoxin-Induced Acute Lung Injury.
Title: Induced Pluripotent Stem Cell-Derived Conditioned Medium Promotes Endogenous Leukemia Inhibitory Factor to Attenuate Endotoxin-Induced Acute Lung Injury.

Submit: New GeneRIF Correction See all GeneRIFs (178)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Common variants at five new loci associated with early-onset inflammatory bowel disease. GeneReviews: Not available
Genome-wide association study identifies susceptibility loci for IgA nephropathy. GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:481059

NoName (e-PCR)
- UniSTS:483713

RH27829 (e-PCR)
- UniSTS:90754

GDB:624823 (e-PCR)
- UniSTS:158363

GDB:625815 (e-PCR)
- UniSTS:158366

SHGC-145300 (e-PCR)
- UniSTS:174504

SHGC-7772 (e-PCR)
- UniSTS:44530

Homology

Homologs of the LIF gene: The LIF gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 273 organisms have orthologs with human gene LIF
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables growth factor activity	IDA Inferred from Direct Assay more info	PubMed
enables leukemia inhibitory factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables leukemia inhibitory factor receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables leukemia inhibitory factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in blood vessel remodeling	IEA Inferred from Electronic Annotation more info
involved_in decidualization	IEA Inferred from Electronic Annotation more info
involved_in embryo implantation	IEA Inferred from Electronic Annotation more info
involved_in immune response	IEA Inferred from Electronic Annotation more info
involved_in leukemia inhibitory factor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in leukemia inhibitory factor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in lung alveolus development	IEA Inferred from Electronic Annotation more info
involved_in lung lobe morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in lung vasculature development	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	TAS Traceable Author Statement more info	PubMed
involved_in muscle organ morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of hormone secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of meiotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in neuron development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of astrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell adhesion mediated by integrin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of histone H3-K27 acetylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of macrophage differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-serine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of RNA polymerase II regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of metanephric nephron tubule epithelial cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in stem cell population maintenance	IEA Inferred from Electronic Annotation more info
involved_in trophoblast giant cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in tyrosine phosphorylation of STAT protein	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in extracellular space	IC Inferred by Curator more info	PubMed

General protein information

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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

NG_008721.1 RefSeqGene

Range

5049..11355

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001257135.2 → NP_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
NM_002309.5 → NP_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

P15018

Related

ENSP00000249075.3, ENST00000249075.4

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p13 Primary Assembly

Range

30240453..30257487 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024452239.1 → XP_024308007.1 leukemia inhibitory factor isoform X1

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor
XM_024452240.1 → XP_024308008.1 leukemia inhibitory factor isoform X1

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor