LEF1 Gene

Name	lymphoid enhancer-binding factor 1
Description	This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LEF1 (lymphoid enhancer factor 1) is a pivotal transcription factor acting downstream of the canonical Wnt/β‐catenin cascade to integrate extracellular signals into specific nuclear gene programs. In hematopoietic stem cells, for example, activation of a LEF1/TCF reporter indicates that Wnt signals promote self‐renewal and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In epithelial cancers, LEF1 is incorporated into nuclear complexes with β‐catenin – as seen following regulated proteolysis of EpCAM – thereby driving the expression of genes that support proliferation and oncogenic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, increased β‐catenin–TCF/LEF1 transcriptional activity—elicited by mechanisms such as downregulation of caveolin‐1 or overexpression of LEF1 itself—has been linked to epithelial–mesenchymal transition (EMT), fostering invasion and metastasis in diverse tumor types"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", with mechanistic support also provided by studies showing that stabilizing nuclear β‐catenin enhances LEF1‐mediated EMT."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In lung adenocarcinoma, LEF1 is identified as a direct target of Wnt/TCF signaling that mediates chemotactic invasion and colony outgrowth, contributing to metastasis to distant sites such as brain and bone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In developmental contexts such as hair follicle morphogenesis, convergent signals from Wnt proteins (which stabilize β‐catenin) and BMP inhibitors induce production of LEF1; the resulting β‐catenin–LEF1 complexes then downregulate adhesion molecules like E‐cadherin to remodel cell–cell contacts, thereby facilitating follicle invagination and differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, transcriptional repressors such as Snail and Slug have been shown to induce LEF1 expression, linking loss of epithelial characteristics with activation of migratory and invasive programs in cancer cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "; indeed, TGF‐β3 signaling can further upregulate LEF1 as part of a cascade that promotes complete EMT."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, in hepatocellular carcinoma, oncogenic events converge to activate Wnt/β‐catenin signaling and upregulate LEF1 (together with related TCF factors), thereby underscoring its contribution to tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while in endothelial cells LEF1 integrates Notch‐derived cues with Wnt signaling to stabilize new vascular connections."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight LEF1 as a multifunctional effector that not only mediates critical aspects of normal stem cell maintenance and tissue morphogenesis but also drives pathological processes such as EMT, invasion, and metastasis across a range of normal and neoplastic cell types."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tannishtha Reya, Andrew W Duncan, Laurie Ailles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for Wnt signalling in self-renewal of haematopoietic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01593"}], "href": "https://doi.org/10.1038/nature01593"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12717450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12717450"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dorothea Maetzel, Sabine Denzel, Brigitte Mack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear signalling by tumour-associated antigen EpCAM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1824"}], "href": "https://doi.org/10.1038/ncb1824"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19136966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19136966"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhimin Lu, Sourav Ghosh, Zhiyong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1535-6108(03)00304-0"}], "href": "https://doi.org/10.1016/s1535-6108(03"}, {"type": "t", "text": "00304-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14706341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14706341"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kwonseop Kim, Zifan Lu, Elizabeth D Hay "}, {"type": "b", "children": [{"type": "t", "text": "Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/cbir.2002.0901"}], "href": "https://doi.org/10.1006/cbir.2002.0901"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12095232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12095232"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Danette L Daniels, William I Weis "}, {"type": "b", "children": [{"type": "t", "text": "Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb912"}], "href": "https://doi.org/10.1038/nsmb912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15768032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15768032"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Don X Nguyen, Anne C Chiang, Xiang H-F Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.04.030"}], "href": "https://doi.org/10.1016/j.cell.2009.04.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19576624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19576624"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Colin Jamora, Ramanuj DasGupta, Pawel Kocieniewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Links between signal transduction, transcription and adhesion in epithelial bud development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01458"}], "href": "https://doi.org/10.1038/nature01458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646922"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jolly Mazumdar, W Timothy O'Brien, Randall S Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "O2 regulates stem cells through Wnt/β-catenin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2102"}], "href": "https://doi.org/10.1038/ncb2102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20852629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20852629"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sandra Guaita, Isabel Puig, Clara Franci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206400200"}], "href": "https://doi.org/10.1074/jbc.M206400200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12161443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12161443"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kevin G Leong, Kyle Niessen, Iva Kulic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20071082"}], "href": "https://doi.org/10.1084/jem.20071082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17984306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17984306"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Damian Medici, Elizabeth D Hay, Bjorn R Olsen "}, {"type": "b", "children": [{"type": "t", "text": "Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e08-05-0506"}], "href": "https://doi.org/10.1091/mbc.e08-05-0506"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18799618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18799618"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Nam Hee Kim, Hyun Sil Kim, Xiao-Yan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201103097"}], "href": "https://doi.org/10.1083/jcb.201103097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22024162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22024162"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Li-Kun Phng, Michael Potente, Jonathan D Leslie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2008.12.009"}], "href": "https://doi.org/10.1016/j.devcel.2008.12.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19154719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19154719"}]}]}]}
Synonyms	TCF10, TCF7L3, TCF1ALPHA, LEF-1
Proteins	LEF1_HUMAN
NCBI Gene ID	51176
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

LEF1 has 14,612 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 136 datasets.

Click the + buttons to view associations for LEF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

LEF1 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 LEF1 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 LEF1 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 LEF1 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 LEF1 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 LEF1 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 LEF1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving LEF1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of LEF1 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 LEF1 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 LEF1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of LEF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of LEF1 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 LEF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with LEF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with LEF1 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 LEF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of LEF1 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 LEF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of LEF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing LEF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing LEF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing LEF1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with LEF1 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 LEF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing LEF1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of LEF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with LEF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with LEF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with LEF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with LEF1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by LEF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with LEF1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with LEF1 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 LEF1 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 LEF1 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 LEF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with LEF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at LEF1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of LEF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of LEF1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.