Details for: TFF3

Gene ID: 7033

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TFF3

Ensembl ID: ENSG00000160180

Description: trefoil factor 3

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestine goblet cell CL0019031
    CSI 75.58
    rCSI 67.09%
    PRS 94.67
  • goblet cell CL0000160
    CSI 51.08
    rCSI 48.27%
    PRS 94.6
  • mucus secreting cell CL0000319
    CSI 45.17
    rCSI 71.74%
    PRS 98.03
  • paneth cell CL0000510
    CSI 44.51
    rCSI 65.71%
    PRS 97.95
  • transit amplifying cell of colon CL0009011
    CSI 35.28
    rCSI 41.43%
    PRS 96.44
  • small intestine goblet cell CL1000495
    CSI 32.92
    rCSI 72.11%
    PRS 96.73
  • ciliated epithelial cell CL0000067
    CSI 29.94
    rCSI 26.33%
    PRS 90.59
  • stem cell CL0000034
    CSI 27.76
    rCSI 26.77%
    PRS 94.38
  • colon goblet cell CL0009039
    CSI 27.34
    rCSI 65%
    PRS 96.47
  • pancreatic A cell CL0000171
    CSI 26.8
    rCSI 28.08%
    PRS 96.64
  • respiratory suprabasal cell CL4033048
    CSI 25.3
    rCSI 32.44%
    PRS 96.92
  • lung neuroendocrine cell CL1000223
    CSI 24.24
    rCSI 35.85%
    PRS 96.21
  • tracheal goblet cell CL1000329
    CSI 23.57
    rCSI 51.46%
    PRS 96.63
  • enteroendocrine cell of small intestine CL0009006
    CSI 23.52
    rCSI 51.79%
    PRS 96.38
  • pulmonary ionocyte CL0017000
    CSI 22.28
    rCSI 27.12%
    PRS 97.4
  • colon epithelial cell CL0011108
    CSI 20.89
    rCSI 21.89%
    PRS 94.7
  • ionocyte CL0005006
    CSI 19.62
    rCSI 21.03%
    PRS 96.6
  • secretory cell CL0000151
    CSI 19.08
    rCSI 19.91%
    PRS 95.53
  • enterocyte CL0000584
    CSI 17.59
    rCSI 28.36%
    PRS 93.58
  • bronchial goblet cell CL1000312
    CSI 17.23
    rCSI 68.86%
    PRS 97.46
  • BEST4+ enteroycte CL4030026
    CSI 16.36
    rCSI 20.35%
    PRS 95.34
  • endothelial cell of lymphatic vessel CL0002138
    CSI 15.52
    rCSI 30.76%
    PRS 96.19
  • enteroendocrine cell CL0000164
    CSI 15.48
    rCSI 21.15%
    PRS 94.17
  • M cell of gut CL0000682
    CSI 15.4
    rCSI 16.37%
    PRS 96.67
  • duct epithelial cell CL0000068
    CSI 14.11
    rCSI 20.64%
    PRS 97.76
  • brush cell CL0002204
    CSI 13.91
    rCSI 27.54%
    PRS 96.49
  • multi-ciliated epithelial cell CL0005012
    CSI 12.73
    rCSI 12.71%
    PRS 92.45
  • epithelial cell of lower respiratory tract CL0002632
    CSI 12.59
    rCSI 9.76%
    PRS 97.54
  • type EC enteroendocrine cell CL0000577
    CSI 12.27
    rCSI 43.56%
    PRS 95.89
  • club cell CL0000158
    CSI 12.27
    rCSI 17.97%
    PRS 94.02
  • epithelial cell CL0000066
    CSI 11.02
    rCSI 16.94%
    PRS 87.21
  • enteroendocrine cell of colon CL0009042
    CSI 10.74
    rCSI 50.34%
    PRS 95.99
  • myeloid leukocyte CL0000766
    CSI 10.57
    rCSI 9.76%
    PRS 97.13
  • lung ciliated cell CL1000271
    CSI 10.51
    rCSI 12.15%
    PRS 92.69
  • epithelial cell of lung CL0000082
    CSI 10.18
    rCSI 8.44%
    PRS 97.07
  • ciliated cell CL0000064
    CSI 9.86
    rCSI 15.97%
    PRS 91.4
  • tuft cell of colon CL0009041
    CSI 9.61
    rCSI 22.38%
    PRS 96.27
  • nasal mucosa goblet cell CL0002480
    CSI 9.44
    rCSI 10.95%
    PRS 95.64
  • intestinal tuft cell CL0019032
    CSI 9.24
    rCSI 14.12%
    PRS 96.29
  • transit amplifying cell CL0009010
    CSI 9.2
    rCSI 14.07%
    PRS 97.37
  • IgA plasma cell CL0000987
    CSI 9.03
    rCSI 9.24%
    PRS 95.33
  • respiratory basal cell CL0002633
    CSI 8.98
    rCSI 9.3%
    PRS 97
  • paneth cell of epithelium of small intestine CL1000343
    CSI 8.51
    rCSI 23.86%
    PRS 97.03
  • colonocyte CL1000347
    CSI 8.25
    rCSI 11.83%
    PRS 94.6
  • pancreatic D cell CL0000173
    CSI 8.21
    rCSI 8.08%
    PRS 96.5
  • fallopian tube secretory epithelial cell CL4030006
    CSI 7.85
    rCSI 7.56%
    PRS 95.15
  • lung endothelial cell CL1001567
    CSI 7.75
    rCSI 18.08%
    PRS 98.23
  • type B pancreatic cell CL0000169
    CSI 7.02
    rCSI 15.54%
    PRS 95.93
  • tracheobronchial serous cell CL0019001
    CSI 6.6
    rCSI 28.49%
    PRS 97
  • stromal cell CL0000499
    CSI 6.43
    rCSI 18.08%
    PRS 94.14
  • type L enteroendocrine cell CL0002279
    CSI 6.01
    rCSI 11.29%
    PRS 96.03
  • acinar cell CL0000622
    CSI 5.79
    rCSI 8.49%
    PRS 98.05
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 5.75
    rCSI 13.11%
    PRS 90.84
  • glial cell CL0000125
    CSI 5.62
    rCSI 21.39%
    PRS 91.94
  • mesodermal cell CL0000222
    CSI 5.42
    rCSI 6.51%
    PRS 96.26
  • enterocyte of epithelium of large intestine CL0002071
    CSI 5.38
    rCSI 28.26%
    PRS 96.43
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 5.29
    rCSI 14.26%
    PRS 96.77
  • deuterosomal cell CL4033044
    CSI 5.16
    rCSI 17.44%
    PRS 91.54
  • paneth cell of colon CL0009009
    CSI 5.03
    rCSI 49.43%
    PRS 97.01
  • foveolar cell of stomach CL0002179
    CSI 4.97
    rCSI 10.58%
    PRS 96.67
  • mesenchymal cell CL0008019
    CSI 4.89
    rCSI 12.42%
    PRS 94.18
  • IgG plasma cell CL0000985
    CSI 4.71
    rCSI 5.64%
    PRS 96.98
  • respiratory goblet cell CL0002370
    CSI 4.64
    rCSI 50.52%
    PRS 97.37
  • luminal epithelial cell of mammary gland CL0002326
    CSI 4.56
    rCSI 8.29%
    PRS 97.96
  • mucous neck cell CL0000651
    CSI 4.49
    rCSI 6.47%
    PRS 96.95
  • lung secretory cell CL1000272
    CSI 4.45
    rCSI 11.01%
    PRS 97.15
  • neuroendocrine cell CL0000165
    CSI 4.45
    rCSI 17.19%
    PRS 96.58
  • intestinal crypt stem cell of colon CL0009043
    CSI 4.12
    rCSI 30.92%
    PRS 97.95
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 4.02
    rCSI 12.39%
    PRS 96.47
  • retinal blood vessel endothelial cell CL0002585
    CSI 3.75
    rCSI 5.99%
    PRS 97.26
  • tracheobronchial goblet cell CL0019003
    CSI 3.23
    rCSI 51.89%
    PRS 95.9
  • intestinal epithelial cell CL0002563
    CSI 2.94
    rCSI 3.08%
    PRS 94.64
  • stratified epithelial cell CL0000079
    CSI 2.89
    rCSI 17.82%
    PRS 96.74
  • pancreatic PP cell CL0002275
    CSI 2.69
    rCSI 10.71%
    PRS 96.5
  • myoepithelial cell CL0000185
    CSI 2.6
    rCSI 6.59%
    PRS 97.31
  • intrahepatic cholangiocyte CL0002538
    CSI 2.58
    rCSI 6.19%
    PRS 95.66
  • pancreatic epsilon cell CL0005019
    CSI 2.56
    rCSI 11.94%
    PRS 96.59
  • respiratory epithelial cell CL0002368
    CSI 2.52
    rCSI 15.53%
    PRS 99.21
  • basal cell of epithelium of trachea CL1000348
    CSI 1.88
    rCSI 13.24%
    PRS 96.16
  • pancreatic ductal cell CL0002079
    CSI 1.65
    rCSI 3.22%
    PRS 96.4
  • luminal cell of prostate epithelium CL0002340
    CSI 1.51
    rCSI 8.14%
    PRS 97.61
  • vasa recta ascending limb cell CL1001131
    CSI 1.45
    rCSI 6.56%
    PRS 97.83
  • erythroblast CL0000765
    CSI 1.45
    rCSI 3.84%
    PRS 95.87
  • mammary gland epithelial cell CL0002327
    CSI 1.14
    rCSI 3.98%
    PRS 97.9
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.79
    rCSI 4.3%
    PRS 96.25
  • acinar cell of salivary gland CL0002623
    CSI 0.77
    rCSI 17.87%
    PRS 98.08
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.57
    rCSI 8.84%
    PRS 96.37

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TFF3](/details-gene/7033) (Trefoil Factor 3) is a protein-coding gene located on chromosome 21q22.3 ([Link](https://pubmed.ncbi.nlm.nih.gov/9070946/)). It encodes a small, secreted protein that is a member of the trefoil factor family, characterized by a unique three-loop "trefoil" domain structure. Functionally, [TFF3](/details-gene/7033) is primarily involved in the protection and repair of mucosal surfaces, particularly in the `[Maintenance of gastrointestinal epithelium](/details-cell/GO:0030277)`. Expression data strongly indicates that [TFF3](/details-gene/7033) is a key marker and major product of mucus-secreting cells, most significantly `[intestine goblet cell](/details-cell/CL0019031)`s. Its presence in the `[Extracellular region](/details-cell/GO:0005576)` is consistent with its role as a secreted factor that stabilizes the mucus layer and promotes epithelial restitution following injury. ## Cellular Roles and Expression Landscape The expression profile of [TFF3](/details-gene/7033) unequivocally establishes its role as a specialized product of mucosal secretory cells. **Overall**, it exhibits the highest significance in `[intestine goblet cell](/details-cell/CL0019031)` (CSI: 75.58), a finding supported by early research identifying it as a goblet-cell specific peptide targeted for apical secretion ([Link](https://pubmed.ncbi.nlm.nih.gov/8454642/)). This high specificity extends to other secretory cell types across different tissues, including `[goblet cell](/details-cell/CL0000160)`s in general, `[mucus secreting cell](/details-cell/CL0000319)`s, and `[tracheal goblet cell](/details-cell/CL1000329)`s. Beyond its primary association with goblet cells, [TFF3](/details-gene/7033) is also significantly expressed in other key epithelial and endocrine cells of the gut, such as `[paneth cell](/details-cell/CL0000510)`, `[transit amplifying cell of colon](/details-cell/CL0009011)`, and `[enteroendocrine cell of small intestine](/details-cell/CL0009006)`. This broad expression pattern within the intestinal epithelium underscores its integral role in maintaining gut homeostasis. Its presence has also been noted in the human uterus ([Link](https://pubmed.ncbi.nlm.nih.gov/8346203/)) and hypothalamus ([Link](https://pubmed.ncbi.nlm.nih.gov/10824705/)), suggesting functions beyond the gastrointestinal tract. ## Pathways and Molecular Function The molecular functions of [TFF3](/details-gene/7033) are directly tied to its role in epithelial barrier function and signaling. As a secreted protein found in the `[Extracellular space](/details-cell/GO:0005615)` and `[Secretory granule](/details-cell/GO:0030141)`, its primary activity occurs outside the cell. It is known to engage in `[Identical protein binding](/details-cell/GO:0042802)`, forming dimers that are believed to be crucial for its function in stabilizing the mucus gel layer ([Link](https://pubmed.ncbi.nlm.nih.gov/14690424/)). Pathway analysis connects [TFF3](/details-gene/7033) to hormone-regulated signaling, particularly `[Esr-mediated signaling](/details-cell/R-HSA-8939211)` and `[Estrogen-dependent gene expression](/details-cell/R-HSA-9018519)`. This suggests its expression may be under the control of nuclear receptors like the estrogen receptor, providing a potential link between hormonal status and mucosal health. Its broader classification under `[Signal transduction](/details-cell/R-HSA-162582)` is consistent with its ability to promote cell migration and repair, for instance, by acting synergistically with epidermal growth factor in bronchial epithelial cells ([Link](https://pubmed.ncbi.nlm.nih.gov/11694446/)). ## Research Directions The specific function of [TFF3](/details-gene/7033) as a secreted, pro-restitutive factor from goblet cells makes it a compelling subject for translational research, particularly in diseases characterized by mucosal barrier dysfunction. **Proposed Testable Hypotheses:** 1. **Hypothesis:** The absence of [TFF3](/details-gene/7033) significantly impairs the initial phase of mucosal wound healing in the colon, not by affecting inflammation, but by directly reducing the rate of epithelial cell migration (restitution) needed to cover the denuded area. 2. **Hypothesis:** Estrogen receptor signaling in `[intestine goblet cell](/details-cell/CL0019031)`s is a primary driver of [TFF3](/details-gene/7033) transcription and secretion, contributing to sex-based differences in susceptibility to inflammatory bowel disease (IBD) or the severity of intestinal mucositis. **Key Experimental Approach:** To test the second hypothesis regarding estrogen regulation, a robust *in vitro* model could be employed. Human colonic organoids, which contain a diverse population of intestinal epithelial cells including goblet cells, would be cultured. These organoids would be treated with 17β-estradiol (an estrogen receptor agonist), tamoxifen (an antagonist), and a vehicle control. The impact on [TFF3](/details-gene/7033) expression would be quantified at both the transcript level (via qPCR) and the protein level (via ELISA of the culture supernatant). This experiment would directly establish a causal link between estrogen signaling and [TFF3](/details-gene/7033) production in the relevant cellular context. **Therapeutic Potential:** Given its natural role in promoting mucosal repair, [TFF3](/details-gene/7033) is a strong candidate for therapeutic **activation** or supplementation, rather than inhibition. Its potential lies in treating conditions of acute or chronic mucosal injury, such as IBD, necrotizing enterocolitis, or chemotherapy-induced oral and gastrointestinal mucositis. The development of a stable, recombinant form of [TFF3](/details-gene/7033) that can be administered orally or topically could represent a novel therapeutic strategy to accelerate epithelial healing and restore barrier integrity in these debilitating conditions.

Genular Protein ID: 1872357251

Symbol: TFF3_HUMAN

Name: Trefoil factor 3

UniProtKB Accession Codes:

Q07654 A0A0A6YYJ4 E9PBB5 Q96NX0 Q9UDA5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UniLectin 1 VEuPathDB 1 eggNOG 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9070946

Title: The three human trefoil genes TFF1, TFF2, and TFF3 are located within a region of 55 kb on chromosome 21q22.3.

PubMed ID: 9070946

DOI: 10.1006/geno.1996.4511

PubMed ID: 10950923

Title: Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region.

PubMed ID: 10950923

DOI: 10.1006/geno.2000.6253

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

PubMed ID: 14637006

Title: mRNA 5' region sequence incompleteness: a potential source of systematic errors in translation initiation codon assignment in human mRNAs.

PubMed ID: 14637006

DOI: 10.1016/s0378-1119(03)00835-7

PubMed ID: 8346203

Title: hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus.

PubMed ID: 8346203

DOI: 10.1073/pnas.90.15.6961

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8454642

Title: Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion.

PubMed ID: 8454642

DOI: 10.1016/s0021-9258(18)53305-6

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 19670903

Title: Comprehensive proteomic analysis of human endometrial fluid aspirate.

PubMed ID: 19670903

DOI: 10.1021/pr9004426

PubMed ID: 10824705

Title: Coexistence of intestinal trefoil factor (hITF) and oxytocin in magnocellular neurons in the human hypothalamus.

PubMed ID: 10824705

DOI: 10.1055/s-2007-978604

PubMed ID: 11694446

Title: Trefoil factor family-peptides promote migration of human bronchial epithelial cells: synergistic effect with epidermal growth factor.

PubMed ID: 11694446

DOI: 10.1165/ajrcmb.25.4.4429

PubMed ID: 18209

Title: Incorporation of mannose and glucose into prenylphosphate sugars in isolated human platelet membranes.

PubMed ID: 18209

DOI: 10.1016/0304-4165(77)90272-0

PubMed ID: 14690424

Title: Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins.

PubMed ID: 14690424

DOI: 10.1021/bi030182k

Sequence Information:

  • Length: 80
  • Mass: 8641
  • Checksum: 8E117A58C0342013
  • Sequence:
    • MAARALCMLG LVLALLSSSS AEEYVGLSAN QCAVPAKDRV DCGYPHVTPK ECNNRGCCFD 
SRIPGVPWCF KPLQEAECTF