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; 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: mouse all
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Genomic context

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_000022.11 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 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?

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.
Title: Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.
Cancer-associated fibroblasts promote the malignant development of lung cancer through the FOXO1 protein/LIF signaling.
Title: Cancer-associated fibroblasts promote the malignant development of lung cancer through the FOXO1 protein/LIF signaling.
Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.
Title: Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.
The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer.
Title: The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer.
Human Seminal Extracellular Vesicles Enhance Endometrial Receptivity Through Leukemia Inhibitory Factor.
Title: Human Seminal Extracellular Vesicles Enhance Endometrial Receptivity Through Leukemia Inhibitory Factor.
LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages.
Title: LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages.
MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.
Title: MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.
Interplay of "leukemia inhibitory factor receptor gene" (rs3099124) polymorphism, leukemia inhibitory factor and ovarian steroids with unexplained infertility.
Title: Interplay of "leukemia inhibitory factor receptor gene" (rs3099124) polymorphism, leukemia inhibitory factor and ovarian steroids with unexplained infertility.
Relevance of leukaemia inhibitory factor to anti-melanoma differentiation-associated gene 5 antibody-positive interstitial lung disease.
Title: Relevance of leukaemia inhibitory factor to anti-melanoma differentiation-associated gene 5 antibody-positive interstitial lung disease.
The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights.
Title: The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights.

Submit: New GeneRIF Correction See all GeneRIFs (192)

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

EBI GWAS Catalog

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

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	IBA Inferred from Biological aspect of Ancestor more info
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
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 cell morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway via STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in decidualization	IEA Inferred from Electronic Annotation more info
involved_in embryo implantation	IEA Inferred from Electronic Annotation more info
involved_in fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in gene expression	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
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 macrophage differentiation	TAS Traceable Author Statement more info	PubMed
involved_in meiotic nuclear division	IEA Inferred from Electronic Annotation more info
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
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 fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
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
acts_upstream_of_or_within positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of receptor signaling pathway via STAT	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 regulation of cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of metanephric nephron tubule epithelial cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in somatic stem cell population maintenance	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in trophoblast giant cell differentiation	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
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

Download

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

B2RCW7, B5MC23, P15018, Q52LZ2

Related

ENSP00000249075.3, ENST00000249075.4

Conserved Domains (1) summary

smart00080
Location:34 → 191

LIF_OSM; leukemia inhibitory factor