LEF1 Gene: Lymphoid Enhancer Binding Factor 1
A key transcription factor in Wnt/β-catenin signaling, implicated in development and cancer
Gene Information Card
| Symbol | LEF1 |
|---|---|
| Full Name | lymphoid enhancer binding factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q25 |
| NCBI Gene ID | 51176 ncbi.nlm.nih.gov/gene/51176 |
| Ensembl ID | ENSG00000138795 |
| UniProt ID | Q9UJU2 |
| OMIM ID | 153245 |
| HGNC ID | 6553 |
| Aliases | TCF7L3, TCF1α, LEF-1 |
Description
LEF1 (lymphoid enhancer binding factor 1) encodes a transcription factor that mediates Wnt/β-catenin signaling by binding to specific DNA sequences in target gene promoters. It plays critical roles in embryonic development, cell fate determination, and immune cell differentiation. Dysregulation of LEF1 is associated with several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | LEF1 acts as a downstream effector of Wnt/β-catenin signaling; aberrant activation promotes tumorigenesis | COSMIC; ClinVar |
| Sebaceous tumors (e.g., sebaceoma) | Somatic mutations in LEF1 lead to constitutive activation of Wnt signaling | ClinVar; OMIM |
| Lymphoid malignancies (e.g., B-cell lymphoma) | LEF1 overexpression drives proliferation and survival of malignant lymphocytes | NCBI Gene; COSMIC |
| Tooth agenesis (selective) | Loss-of-function variants impair Wnt signaling during odontogenesis | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 10.8 | High |
| Bone marrow | 9.2 | High |
| Colon | 4.1 | Medium |
| Small intestine | 3.8 | Medium |
| Brain | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 8.7 | Embryonic kidney; high expression |
| K562 | 6.2 | Leukemia; moderate expression |
| HCT116 | 5.1 | Colorectal carcinoma; moderate expression |
| MCF7 | 2.3 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.146C>T (p.Pro49Leu) | Missense | 0.2% in colorectal cancer | Alters DNA-binding domain; may affect transcriptional activity |
| c.382_383insA (p.Thr128Asnfs*5) | Frameshift | Rare in sebaceous tumors | Loss of function; truncation of protein |
| c.997G>A (p.Glu333Lys) | Missense | 0.1% in lymphoid malignancies | Gain-of-function; enhances β-catenin interaction |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr128Asnfs*5) that truncate the protein and abolish DNA binding or transactivation.
Gain of Function (GOF)
Missense mutations (e.g., p.Glu333Lys) that increase affinity for β-catenin or enhance transcriptional activity.
Dominant Negative (DN)
Some missense mutations in the HMG box may produce proteins that bind DNA but fail to activate transcription, interfering with wild-type LEF1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• TCF/LEF-dependent transcription (Reactome: R-HSA-201681)
• Colorectal cancer (KEGG: hsa05210)
Protein Summary
LEF1 is a 399-amino acid transcription factor containing an N-terminal β-catenin binding domain, a central HMG box DNA-binding domain, and a C-terminal context-dependent activation/repression domain. It forms nuclear complexes with β-catenin to regulate genes involved in cell proliferation, differentiation, and stemness. Alternative splicing generates isoforms with distinct functional properties.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LEF1 Knockout HEK293 Cell Line | EDJ-KQ312 | Human | 51176 | Details Get a Quote |
| LEF1 Knockout HeLa Cell Line | EDJ-KQ56243 | Human | 51176 | Details Get a Quote |
| LEF1 Knockout A-549 Cell Line | EDJ-KQ64732 | Human | 51176 | Details Get a Quote |
| LEF1 Knockout HCT 116 Cell Line | EDJ-KQ73177 | Human | 51176 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
