TFF3: Trefoil Factor 3 – A Key Mucosal Repair and Tumor Biomarker
Comprehensive genomic and proteomic overview of TFF3, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | TFF3 |
|---|---|
| Full Name | Trefoil Factor 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 7033 ncbi.nlm.nih.gov/gene/7033 |
| Ensembl ID | ENSG00000160180 |
| UniProt ID | Q07654 |
| OMIM ID | 600933 |
| HGNC ID | 11757 |
| Aliases | ITF, hITF, TFI, trefoil factor 3 (intestinal) |
Description
TFF3 (Trefoil Factor 3) encodes a small secreted protein belonging to the trefoil factor family. It is primarily expressed in the gastrointestinal tract, where it plays a critical role in mucosal protection, repair, and regeneration. TFF3 is also implicated in cancer progression and metastasis, particularly in colorectal, gastric, and breast cancers. The protein contains a characteristic trefoil domain that stabilizes the mucus layer and promotes epithelial restitution.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Overexpression of TFF3 promotes cell migration, invasion, and resistance to anoikis, contributing to metastasis. | PMID: 23454724; COSMIC TFF3 overexpression in colorectal tumors |
| Gastric Cancer | TFF3 is upregulated in gastric adenocarcinomas and associated with poor prognosis; may activate PI3K/Akt signaling. | PMID: 20648617; ClinVar: TFF3 expression in gastric cancer |
| Breast Cancer | TFF3 expression correlates with estrogen receptor status and is linked to endocrine therapy resistance. | PMID: 21573175; COSMIC: TFF3 mutations in breast cancer |
| Inflammatory Bowel Disease | TFF3 is induced during mucosal injury and promotes epithelial repair; reduced expression may impair healing. | PMID: 10655569; NCBI Gene: TFF3 in IBD |
| Ulcerative Colitis | Altered TFF3 expression in colonic mucosa contributes to barrier dysfunction and chronic inflammation. | PMID: 11846417; OMIM: 600933 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 112.3 | High |
| Small Intestine | 89.7 | High |
| Stomach | 45.2 | Medium |
| Breast | 12.1 | Low |
| Lung | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HT-29 (colorectal adenocarcinoma) | 98.5 | High expression; used in TFF3 functional studies |
| MCF-7 (breast adenocarcinoma) | 22.3 | Moderate expression; estrogen-responsive |
| A549 (lung carcinoma) | 1.2 | Very low expression |
| HCT 116 (colorectal carcinoma) | 76.8 | High expression; TFF3 knockdown reduces migration |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.1% | Potential loss of start codon; likely loss-of-function |
| c.184C>T (p.Arg62Trp) | missense | <0.1% | Located in trefoil domain; may affect protein stability |
| c.256G>A (p.Gly86Ser) | missense | <0.1% | Rare variant; functional impact unknown |
| c.319_320insA (p.Thr107Asnfs*2) | frameshift | <0.1% | Predicted loss-of-function via nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations (e.g., c.1A>G, c.319_320insA) are predicted to cause loss of TFF3 protein function, impairing mucosal repair.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression in cancer is primarily transcriptional.
Dominant Negative (DN)
No dominant-negative mutations described for TFF3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K-Akt signaling pathway (Reactome: R-HSA-1257604)
• Mucin-type O-glycan biosynthesis (KEGG: hsa00512)
• Gastric cancer network (KEGG: hsa05226)
• Trefoil factor family signaling (UniProt: Q07654)
Protein Summary
TFF3 is a 59-amino acid secreted protein containing a single trefoil domain (P-domain) stabilized by three disulfide bonds. It is produced mainly by goblet cells in the intestine and colon, and by mucous cells in the stomach. TFF3 interacts with mucins (e.g., MUC2) to enhance mucus viscosity and barrier function. It also promotes epithelial cell migration and survival through activation of EGFR, PI3K/Akt, and MAPK pathways. In cancer, TFF3 overexpression is associated with invasion, metastasis, and chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TFF3 Knockout HEK293 Cell Line | EDJ-KQ3912 | Human | 7033 | Details Get a Quote |
| TFF3 Knockout HeLa Cell Line | EDJ-KQ54646 | Human | 7033 | Details Get a Quote |
| TFF3 Knockout A-549 Cell Line | EDJ-KQ63126 | Human | 7033 | Details Get a Quote |
| TFF3 Knockout HCT 116 Cell Line | EDJ-KQ71599 | Human | 7033 | Details Get a Quote |
