LIFR Gene

HGNC Family	CD molecules (CD), Fibronectin type III domain containing
Name	leukemia inhibitory factor receptor alpha
Description	This gene encodes a protein that belongs to the type I cytokine receptor family. This protein combines with a high-affinity converter subunit, gp130, to form a receptor complex that mediates the action of the leukemia inhibitory factor, a polyfunctional cytokine that is involved in cellular differentiation, proliferation and survival in the adult and the embryo. Mutations in this gene cause Schwartz-Jampel syndrome type 2, a disease belonging to the group of the bent-bone dysplasias. A translocation that involves the promoter of this gene, t(5;8)(p13;q12) with the pleiomorphic adenoma gene 1, is associated with salivary gland pleiomorphic adenoma, a common type of benign epithelial tumor of the salivary gland. Multiple splice variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2018]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leukemia inhibitory factor receptor (LIFR) is a multifunctional component of cytokine receptor complexes for members of the interleukin‐6 family that, upon ligand binding, couples to gp130 to activate intracellular signaling cascades—most notably the JAK/STAT pathway. In breast cancer, LIFR functions as a metastasis suppressor by triggering a Hippo kinase cascade that results in the phosphorylation and cytoplasmic retention of YAP, thereby inhibiting cancer cell migration, invasion, and colonization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In embryonic stem cells, LIFR‐mediated STAT3 activation is critical for sustaining self‐renewal in the mouse, although similar signaling in human ESCs—despite effective STAT3 phosphorylation—is insufficient to maintain pluripotency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Beyond stem cell biology, LIFR plays essential roles during development. It is a key mediator of LIF’s pleiotropic functions that include maternal receptivity, placental morphogenesis, and nervous system development, with studies also demonstrating LIFR as a necessary partner in neuropoietin‐induced neurotrophic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Disruption of LIFR function, as evidenced by null mutations causing Stuve–Wiedemann syndrome, underscores its critical role in skeletal and placental formation by impairing JAK/STAT3 signal transduction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, proper expression of LIFR in both the endometrium and the blastocyst is associated with successful embryo implantation, while deficiencies correlate with implantation failures."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, LIFR participates in defining ligand specificity, as illustrated by its role in receptor complexes that mediate responses to neurotrophic factors such as neuropoietin and ciliary neurotrophic factor, thereby fine‐tuning cellular outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, in the context of nasopharyngeal carcinoma, overexpression of LIFR (in concert with elevated levels of LIF) contributes to tumor growth and radioresistance through activation of the mTORC1/p70S6K signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings highlight LIFR’s diverse roles in regulating cell fate during development and in modulating tumor progression, making it a promising prognostic marker and therapeutic target in oncology and regenerative medicine.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dahu Chen, Yutong Sun, Yongkun Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2940"}], "href": "https://doi.org/10.1038/nm.2940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23001183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23001183"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Laurence Dahéron, Sarah L Opitz, Holm Zaehres, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/stemcells.22-5-770"}], "href": "https://doi.org/10.1634/stemcells.22-5-770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15342941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15342941"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicos A Nicola, Jeffrey J Babon "}, {"type": "b", "children": [{"type": "t", "text": "Leukemia inhibitory factor (LIF)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytokine Growth Factor Rev (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cytogfr.2015.07.001"}], "href": "https://doi.org/10.1016/j.cytogfr.2015.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26187859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26187859"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Damien Derouet, François Rousseau, Fabienne Alfonsi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0306178101"}], "href": "https://doi.org/10.1073/pnas.0306178101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15051883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15051883"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yutaka Takahashi, Nick Carpino, James C Cross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg057"}], "href": "https://doi.org/10.1093/emboj/cdg057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12554639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12554639"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lusine Aghajanova "}, {"type": "b", "children": [{"type": "t", "text": "Leukemia inhibitory factor and human embryo implantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1196/annals.1335.020"}], "href": "https://doi.org/10.1196/annals.1335.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15731310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15731310"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Björn Schuster, Marina Kovaleva, Yi Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.m210044200"}], "href": "https://doi.org/10.1074/jbc.m210044200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12643274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12643274"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shu-Chen Liu, Ngan-Ming Tsang, Wen-Che Chiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI63428"}], "href": "https://doi.org/10.1172/JCI63428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24270418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24270418"}]}]}]}
Synonyms	SJS2, STWS, LIF-R, CD118
Proteins	LIFR_HUMAN
NCBI Gene ID	3977
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LIFR has 7,437 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for LIFR from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LIFR Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LIFR gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of LIFR gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of LIFR gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of LIFR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of LIFR gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of LIFR gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LIFR gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LIFR gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of LIFR gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LIFR gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of LIFR gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with LIFR gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LIFR protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LIFR gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LIFR gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LIFR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of LIFR gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with LIFR gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with LIFR gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LIFR gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LIFR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LIFR protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LIFR protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing LIFR protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LIFR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with LIFR protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing LIFR protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LIFR gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LIFR gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LIFR gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LIFR gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with LIFR gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of LIFR protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LIFR gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving LIFR gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LIFR gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with LIFR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with LIFR gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with LIFR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LIFR gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.