TFF3

Summary

TFF3 (trefoil factor 3, HGNC:11757) is a protein-coding gene on chromosome 21q22.3, encoding Trefoil factor 3 (Q07654). Involved in the maintenance and repair of the intestinal mucosa. In precision oncology, TFF3 EXPRESSION confers sensitivity to Aminoglutethimide + Tamoxifen in Breast Cancer (CIViC Level B).

Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is expressed in goblet cells of the intestines and colon. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.

Source: NCBI Gene 7033 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_003226

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11757
Approved symbol	TFF3
Name	trefoil factor 3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	HITF, ITF
Ensembl gene	ENSG00000160180
Ensembl biotype	protein_coding
OMIM	600633
Entrez	7033

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000398431, ENST00000489676, ENST00000518498, ENST00000891173

RefSeq mRNA: 1 — MANE Select: NM_003226 NM_003226

CCDS: CCDS33565

Canonical transcript exons

ENST00000518498 — 3 exons

Exon	Start	End
ENSE00001312206	42315293	42315409
ENSE00001317813	42313485	42313631
ENSE00001833121	42311667	42312269

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 99.87.

FANTOM5 (CAGE): breadth broad, TPM avg 31.3577 / max 4175.0404, expressed in 408 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190603	28.2104	343
190601	1.7153	157
190604	0.7003	230
190600	0.2829	37
190599	0.2064	23
190597	0.1185	76
190598	0.1031	15
190602	0.0208	9

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.87	gold quality
ileal mucosa	UBERON:0000331	99.86	gold quality
left lobe of thyroid gland	UBERON:0001120	99.79	gold quality
pancreatic ductal cell	CL:0002079	99.72	gold quality
right lobe of thyroid gland	UBERON:0001119	99.66	gold quality
thyroid gland	UBERON:0002046	99.62	gold quality
rectum	UBERON:0001052	99.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.45	gold quality
right uterine tube	UBERON:0001302	98.96	gold quality
colonic mucosa	UBERON:0000317	98.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.67	gold quality
trachea	UBERON:0003126	98.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.11	gold quality
bronchus	UBERON:0002185	97.82	gold quality
epithelium of bronchus	UBERON:0002031	97.81	gold quality
bronchial epithelial cell	CL:0002328	97.71	gold quality
transverse colon	UBERON:0001157	97.60	gold quality
gall bladder	UBERON:0002110	97.52	gold quality
endometrium epithelium	UBERON:0004811	97.51	gold quality
small intestine	UBERON:0002108	97.23	gold quality
duodenum	UBERON:0002114	97.03	gold quality
jejunal mucosa	UBERON:0000399	96.70	gold quality
minor salivary gland	UBERON:0001830	95.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.02	gold quality
intestine	UBERON:0000160	94.48	gold quality
large intestine	UBERON:0000059	94.06	gold quality
nasal cavity mucosa	UBERON:0001826	93.98	gold quality
colon	UBERON:0001155	93.81	gold quality
nasal cavity epithelium	UBERON:0005384	92.89	gold quality
vermiform appendix	UBERON:0001154	92.39	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	88020.84
E-MTAB-9906	yes	41795.35
E-MTAB-8410	yes	33593.32
E-MTAB-6701	yes	27298.53
E-CURD-122	yes	26633.06
E-CURD-46	yes	24504.42
E-MTAB-8221	yes	19906.82
E-MTAB-10283	yes	19230.53
E-CURD-88	yes	18214.64
E-MTAB-8495	yes	11464.22
E-HCAD-15	yes	9346.29
E-MTAB-6653	yes	6528.43
E-GEOD-130148	yes	6503.76
E-CURD-114	yes	6038.06
E-HCAD-11	yes	5300.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CDX2, CEBPB, ERG, GATA6, HIF1A, JUN, NCOA2, NFKB1, NFKB, RELA, STAT3, STAT6

miRNA regulators (miRDB)

28 targeting TFF3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-410-5P	96.55	66.28	459
HSA-MIR-323B-5P	96.12	66.39	472
HSA-MIR-494-5P	95.31	66.29	463

Literature-anchored findings (GeneRIF, showing 40)

• This is the first study to correlate ITF expression with clinicopathological features or outcome in any cancer type. (PMID:12006524)
• expression of ITF may play an important role in bile duct damage because in small bile ducts, production is absent, making such cells vulnerable and providing a thesis for the loss of small, but not large, bile ducts in primary biliary cirrhosis. (PMID:12395334)
• Expressed in conjunctiva in goblet cells. Review. (PMID:12613926)
• secreted trefoil factor 3 is not deficient in premature infants and can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation (PMID:12663147)
• The solution structure of the TFF3 dimer has been determined and compared with the structure of the TFF3 monomer and with other trefoil dimer structures (TFF1 and TFF2) and is found to be markedly different from other trefoil proteins. (PMID:14690424)
• TFF3 has important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa. (PMID:14968359)
• decreased expression of TFF3 mRNA is a marker of follicular thyroid carcinomas, especially those with a high risk of invasion or metastasis (PMID:15083192)
• Decreases in the CRABP1 (cellular retinoic acid binding protein 1) and TFF3 (trefoil factor 3) expression levels identified these as candidate molecular biomarkers for papillary thyroid carcinoma. (PMID:15515157)
• The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. (PMID:15578191)
• TFF3 overexpression may be a critical process in mouse and human hepatocellular carcinogenesis (PMID:15645121)
• TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. (PMID:15665295)
• PI3-K, but not the Stat6 promotes the expression of TFF3 and MUC2 and that the PI3-K pathway may play a pivotal role in intestinal goblet cell differentiation. (PMID:15733066)
• TFF-3 is commonly expressed in hepatocellular carcinoma and its expression correlates with tumor grade (PMID:16110118)
• MUC5AC and MUC2, TFF1 and TFF3, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum (PMID:16142311)
• TFF1, TFF2, TFF3 and MUC5AC may have roles in pathogenesis of pterygium goblet cells (PMID:16142316)
• Expression of TFF3 had a significant correlation with patient age, the number and the area of microvessels. (PMID:16166422)
• The expression of TFF3 in chronic graft-versus-host disease of the liver is increased in response to bile duct damage and repair. (PMID:16278592)
• Van Gogh-like protein 1 (VANGL) is serine/threonine phosphorylated in response to ITF stimulation (PMID:16410243)
• D21S1893-D21S1890 region may harbor candidate genes especially TFF (TFF1, TFF2, and TFF3) and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. (PMID:16830362)
• These results indicate that TFF3 is able to induce ciliogenesis and to promote airway epithelial ciliated cell differentiation, in part through an epidermal growth factor receptor-dependent pathway. (PMID:17008636)
• Plays a role in the regulation of intestinal barrier function by altering the claudin composition within tight junctions, thus decreasing paracellular permeability of the intestinal mucosa. (PMID:17018241)
• This is the first report of TFF3 as a typical secretory peptide of esophageal submucosal glands and gastric cardia. (PMID:17216196)
• Data show that expression of intestinal trefoil factor is significantly related to gastrointestinal functional failure in critical illness children. (PMID:17217669)
• TFF3, in contrast to epidermal growth factor, enhanced a collective cell migration ensuring a precise coverage of the re-populated area avoiding gaps (PMID:17762162)
• Findings reveal a novel TFF3-mediated pathway for stimulation of beta-cell replication that could ultimately be exploited for expansion or preservation of islet beta-cell mass. (PMID:18258687)
• reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds (PMID:18326859)
• is secreted from the submandibular gland and is present in whole saliva; increased the migration of both normal oral keratinocytes and the cancer cell line D12; is likely to contribute to oral wound healing (PMID:18353006)
• TFF was present in term and preterm human milk with rapidly declining concentrations during the first weeks post partum. (PMID:18502057)
• Development of TFF3-based diagnostic methods is now ongoing and it may not be long before thyroid follicular carcinoma can be diagnosed preoperatively using an aspirated sample from the tumor. (PMID:18506086)
• Patients harbouring G3-endometrioid endometrial carcinomas had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients or patients harbouring endometrial hyperplasia (PMID:18682706)
• TFF3 contributes to the malignant behavior of colon cancer cells. (PMID:18979216)
• circulating TFFs are not candidate markers of trisomy 21 in first-trimester pregnancies (PMID:19172695)
• hTFF3 administered to mice decreased tissue TNF-alpha, TLR4, NF-kappaB production, and TLR4, NF-kappaB mRNA expression (PMID:19238529)
• Follicular neoplastic lesions of the thyroid gland have decreased expression of TFF3 compared to normal thyroid tissue, suggesting that TFF3 may have a role in normal thyroid tissue. (PMID:19528408)
• TFF1, TFF2, and TFF3 expression were localized systematically in surgical specimens from the urinary tract. (PMID:20063012)
• Overexpression and promoter hypomethylation of TFF3 is associated with prostate cancer. (PMID:20112343)
• Data show that genes overexpressed in breast carcinoma including TFF1, TFF3, FOXA1 and CA12. (PMID:20132413)
• IL-6/STAT3/TFF3 signaling is involved in human biliary epithelial cell migration and wound healing. (PMID:20229017)
• The expression of hITF mRNA is increased in Crohn’s disease (PMID:20499178)
• TFF3 gene expression was increased in the terminal ileum. Immunohistochemistry showed that some goblet cells did not include TFF3 in the jejunum and that TFF3-positive goblet cells increased toward the terminal ileum. (PMID:21125297)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tff3	ENSMUSG00000024029
rattus_norvegicus	Tff3	ENSRNOG00000001159

Paralogs (2): TFF2 (ENSG00000160181), TFF1 (ENSG00000160182)

Protein

Protein identifiers

Trefoil factor 3 — Q07654 (reviewed: Q07654)

Alternative names: Intestinal trefoil factor, Polypeptide P1.B

All UniProt accessions (2): Q07654, H7BYT0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maintenance and repair of the intestinal mucosa. Promotes the mobility of epithelial cells in healing processes (motogen).

Subunit / interactions. Monomer. Homodimer; disulfide-linked.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Cytoplasm.

Tissue specificity. Expressed in goblet cells of the intestines and colon (at protein level). Expressed by goblet cells of small and large intestinal epithelia and also by the uterus. Also expressed in the hypothalamus where it is detected in paraventricular, periventricular and supraoptic nuclei (at protein level).

RefSeq proteins (1): NP_003217* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000519	P_trefoil_dom	Domain
IPR017957	P_trefoil_CS	Conserved_site
IPR017994	P_trefoil_chordata	Family
IPR044913	P_trefoil_dom_sf	Homologous_superfamily

Pfam: PF00088

UniProt features (17 total): strand 4, disulfide bond 4, helix 3, turn 2, signal peptide 1, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6V1C	X-RAY DIFFRACTION	1.55
1E9T	SOLUTION NMR
1PE3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07654-F1	81.67	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 32–58, 42–57, 52–69, 78

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-162582	Signal Transduction
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 201 (showing top): GOBP_DIGESTION, MODULE_92, HARRIS_HYPOXIA, XU_GH1_AUTOCRINE_TARGETS_UP, GOCC_SECRETORY_GRANULE, BECKER_TAMOXIFEN_RESISTANCE_UP, GOZGIT_ESR1_TARGETS_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, BORLAK_LIVER_CANCER_EGF_UP, BROWNE_HCMV_INFECTION_24HR_UP, MODULE_75, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, SMID_BREAST_CANCER_LUMINAL_B_UP

GO Biological Process (2): regulation of glucose metabolic process (GO:0010906), maintenance of gastrointestinal epithelium (GO:0030277)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), secretory granule (GO:0030141), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ESR-mediated signaling	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
epithelial structure maintenance	1
digestive system process	1
protein binding	1
binding	1
endomembrane system	1
secretory vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFF3	ZNF185	O15231	923
TFF3	MUC2	Q02817	894
TFF3	FCGBP	Q9Y6R7	834
TFF3	MUC5AC	P98088	792
TFF3	CXCR4	P30991	752
TFF3	LINGO2	Q7L985	741
TFF3	HAVCR1	Q96D42	717
TFF3	MUC6	Q6W4X9	690
TFF3	VANGL1	Q8TAA9	687
TFF3	AGR2	O95994	679
TFF3	ZG16	O60844	656
TFF3	REG4	Q9BYZ8	654
TFF3	B2M	P01884	637
TFF3	TFF1	P04155	597
TFF3	DMBT1	Q9UGM3	587

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TFF3	PCBD1	psi-mi:“MI:0915”(physical association)	0.720
PCBD1	TFF3	psi-mi:“MI:0915”(physical association)	0.720
TFF3	TFF3	psi-mi:“MI:0915”(physical association)	0.590
TFF3	FCGBP	psi-mi:“MI:0915”(physical association)	0.590
SGTA	TFF3	psi-mi:“MI:0915”(physical association)	0.560
TFF3	SGTA	psi-mi:“MI:0915”(physical association)	0.560
TFF3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
TFF3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
TFF3	PCBD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): TFF3 (Two-hybrid), TFF3 (Two-hybrid), ZSCAN9 (Two-hybrid), AKR1C1 (Two-hybrid), TFF3 (Two-hybrid), TFF3 (Two-hybrid), ZSCAN9 (Affinity Capture-Western), AKR1C1 (Affinity Capture-Western), PCBD1 (Two-hybrid), UBQLN2 (Two-hybrid), TFF3 (Affinity Capture-MS)

ESM2 similar proteins: A8YXX7, B4X8D9, O46655, O75711, O76095, O77049, O88745, O88823, O88824, P01186, P01359, P04155, P08163, P08833, P0CW02, P18406, P21743, P21744, P22934, P24593, P24594, P25118, P35455, P47876, P47879, P55773, Q03191, Q03403, Q05717, Q07079, Q07654, Q08423, Q16663, Q28985, Q29183, Q62395, Q63467, Q66IA6, Q6DGP8, Q6Q484

Diamond homologs: A8YXX7, B4X8D9, P01359, P04155, P10667, P17437, Q00222, Q00223, Q03191, Q03403, Q03404, Q05049, Q07654, Q08423, Q09030, Q29183, Q62395, Q63467, Q863B4, Q863J2, Q863T4, B3EWZ5, B3EWZ6, Q9MYM4, P10253, Q5R7A9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDX2	“up-regulates quantity by expression”	TFF3	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

10 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

445 predictions. Top by Δscore:

Variant	Effect	Δscore
21:42315287:ACT:A	donor_loss	1.0000
21:42315288:CTC:C	donor_loss	1.0000
21:42315289:TCACA:T	donor_loss	1.0000
21:42315291:A:AC	donor_gain	1.0000
21:42315292:C:CC	donor_gain	1.0000
21:42315292:C:CG	donor_loss	1.0000
21:42315292:CA:C	donor_gain	1.0000
21:42315305:A:AC	donor_gain	1.0000
21:42315305:ACT:A	donor_gain	1.0000
21:42315306:C:CC	donor_gain	1.0000
21:42315306:CTC:C	donor_gain	1.0000
21:42312266:CATT:C	acceptor_gain	0.9900
21:42312268:TT:T	acceptor_gain	0.9900
21:42312270:C:CC	acceptor_gain	0.9900
21:42313629:CAG:C	acceptor_gain	0.9900
21:42313632:C:CC	acceptor_gain	0.9900
21:42315287:A:AC	donor_gain	0.9900
21:42315288:C:CC	donor_gain	0.9900
21:42315292:CACA:C	donor_gain	0.9900
21:42315306:CT:C	donor_gain	0.9900
21:42312267:ATTCT:A	acceptor_loss	0.9800
21:42312268:TTC:T	acceptor_loss	0.9800
21:42312269:TC:T	acceptor_loss	0.9800
21:42312270:C:G	acceptor_loss	0.9800
21:42312271:T:A	acceptor_loss	0.9800
21:42315292:CACAG:C	donor_gain	0.9800
21:42315308:C:CA	donor_gain	0.9800
21:42312265:GCATT:G	acceptor_gain	0.9700
21:42312266:CATTC:C	acceptor_gain	0.9700
21:42312267:ATT:A	acceptor_gain	0.9700

AlphaMissense

602 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:42313504:G:C	F84L	0.996
21:42313504:G:T	F84L	0.996
21:42313506:A:G	F84L	0.996
21:42313537:A:C	F73L	0.992
21:42313537:A:T	F73L	0.992
21:42313539:A:G	F73L	0.992
21:42313505:A:C	F84C	0.990
21:42313559:C:G	C66S	0.986
21:42313560:A:T	C66S	0.986
21:42313508:C:G	C83S	0.983
21:42313509:A:T	C83S	0.983
21:42313619:C:G	C46S	0.981
21:42313620:A:T	C46S	0.981
21:42313597:C:A	R53S	0.980
21:42313597:C:G	R53S	0.980
21:42313538:A:C	F73C	0.978
21:42313505:A:G	F84S	0.973
21:42313506:A:T	F84I	0.969
21:42313544:C:G	C71S	0.969
21:42313545:A:T	C71S	0.969
21:42313510:C:A	W82C	0.967
21:42313510:C:G	W82C	0.967
21:42313589:C:G	C56S	0.967
21:42313590:A:T	C56S	0.967
21:42313541:C:G	C72S	0.966
21:42313542:A:T	C72S	0.966
21:42313509:A:G	C83R	0.965
21:42313506:A:C	F84V	0.961
21:42313589:C:T	C56Y	0.961
21:42313559:C:A	C66F	0.960

dbSNP variants (sampled 300 via entrez): RS1000015244 (21:42313830 G>A,C), RS1000069069 (21:42313538 A>C), RS1000126735 (21:42313430 G>A), RS1001453948 (21:42314384 T>G), RS1001505873 (21:42314141 T>A,C), RS1002513746 (21:42315363 T>C), RS1002581599 (21:42314875 T>C), RS1002694824 (21:42314526 A>C,G), RS1004148895 (21:42315180 A>G), RS1004365714 (21:42313169 G>A), RS1005705731 (21:42316707 G>A), RS1005713536 (21:42311281 C>G,T), RS1006304862 (21:42314428 A>T), RS1006664261 (21:42314656 C>A,G), RS1007655950 (21:42315525 G>A)

Disease associations

OMIM: gene MIM:600633 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009307_18	Spatial memory	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
TFF3 EXPRESSION	Aminoglutethimide + Tamoxifen	Breast Cancer	Sensitivity/Response	CIViC B	EID823

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment	5
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	3
Tobacco Smoke Pollution	affects expression, decreases expression	2
Fenretinide	decreases expression	2
fluxapyroxad	increases expression	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
deoxynivalenol	affects expression, affects reaction, decreases secretion	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
enilconazole	decreases expression	1
sodium arsenite	increases expression	1
tetrathiomolybdate	decreases expression	1
tobacco tar	decreases expression	1
sulindac sulfide	decreases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	increases expression	1
octa-2,4,6-trienoic acid	decreases expression	1
SB 203580	affects reaction, affects expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects expression, affects reaction	1
alisol A 24-acetate	increases expression	1
diphenylarsinic acid	increases secretion	1
alisol B 23-acetate	increases expression	1
LG 100815	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	decreases expression	1
Acetaminophen	decreases expression	1
Adenine	affects expression, affects reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B9C7	Abcam MCF-7 TFF3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.