TCF7

Summary

TCF7 (transcription factor 7, HGNC:11639) is a protein-coding gene on chromosome 5q31.1, encoding Transcription factor 7 (P36402). Transcriptional activator involved in T-cell lymphocyte differentiation.

This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling.

Source: NCBI Gene 6932 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• Transcription factor: yes — 25 downstream targets (CollecTRI)
• MANE Select transcript: NM_003202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11639
Approved symbol	TCF7
Name	transcription factor 7
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	TCF-1
Ensembl gene	ENSG00000081059
Ensembl biotype	protein_coding
OMIM	189908
Entrez	6932

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000342854, ENST00000378560, ENST00000395023, ENST00000395029, ENST00000517478, ENST00000517741, ENST00000517799, ENST00000517851, ENST00000517855, ENST00000518887, ENST00000518915, ENST00000519037, ENST00000519165, ENST00000519238, ENST00000519447, ENST00000520652, ENST00000520699, ENST00000520958, ENST00000521639, ENST00000521970, ENST00000522375, ENST00000522561, ENST00000522653, ENST00000524342, ENST00000851078

RefSeq mRNA: 8 — MANE Select: NM_003202 NM_001134851, NM_001346425, NM_001346450, NM_001366502, NM_003202, NM_201632, NM_201634, NM_213648

CCDS: CCDS4169, CCDS4170, CCDS43362, CCDS47263

Canonical transcript exons

ENST00000342854 — 10 exons

Exon	Start	End
ENSE00002233903	134114681	134115155
ENSE00002258750	134115321	134115387
ENSE00003491365	134138951	134139038
ENSE00003531994	134143592	134143640
ENSE00003538510	134142721	134142883
ENSE00003555314	134142993	134143100
ENSE00003616545	134138059	134138164
ENSE00003623581	134115909	134116033
ENSE00003784327	134142185	134142304
ENSE00004283655	134146224	134148210

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7618 / max 1819.5917, expressed in 1377 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58535	18.9469	1346
58539	5.2859	136
58540	1.1447	84
58536	0.3448	172
58547	0.2197	73
203684	0.1827	85
58538	0.1530	70
58544	0.1373	47
58537	0.1196	50
58543	0.1020	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	99.21	gold quality
olfactory bulb	UBERON:0002264	97.36	silver quality
periodontal ligament	UBERON:0008266	97.30	gold quality
lymph node	UBERON:0000029	97.26	gold quality
right uterine tube	UBERON:0001302	97.24	gold quality
type B pancreatic cell	CL:0000169	96.70	gold quality
granulocyte	CL:0000094	95.98	gold quality
caecum	UBERON:0001153	95.75	gold quality
vermiform appendix	UBERON:0001154	95.71	gold quality
blood	UBERON:0000178	95.39	gold quality
cardia of stomach	UBERON:0001162	95.06	gold quality
cervix squamous epithelium	UBERON:0006922	94.96	silver quality
buccal mucosa cell	CL:0002336	94.83	silver quality
tendon of biceps brachii	UBERON:0008188	94.78	silver quality
ileal mucosa	UBERON:0000331	94.23	gold quality
pancreatic ductal cell	CL:0002079	94.19	gold quality
superficial temporal artery	UBERON:0001614	93.69	gold quality
oviduct epithelium	UBERON:0004804	93.66	gold quality
pylorus	UBERON:0001166	93.55	gold quality
upper arm skin	UBERON:0004263	93.53	silver quality
corpus epididymis	UBERON:0004359	93.45	gold quality
cervix epithelium	UBERON:0004801	93.40	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.19	gold quality
pigmented layer of retina	UBERON:0001782	93.16	gold quality
choroid plexus epithelium	UBERON:0003911	93.11	gold quality
caput epididymis	UBERON:0004358	92.92	gold quality
triceps brachii	UBERON:0001509	92.55	silver quality
vena cava	UBERON:0004087	92.49	gold quality
superior surface of tongue	UBERON:0007371	92.48	gold quality
bone marrow cell	CL:0002092	92.32	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	1856.57
E-GEOD-150728	yes	1201.56
E-MTAB-9221	yes	695.50
E-ANND-5	yes	631.46
E-CURD-122	yes	436.87
E-MTAB-8911	yes	428.20
E-CURD-112	yes	421.75
E-GEOD-149689	yes	408.64
E-CURD-55	yes	403.82
E-CURD-89	yes	374.53
E-HCAD-4	yes	87.85
E-CURD-88	yes	49.41
E-HCAD-8	yes	48.58
E-HCAD-10	yes	24.12
E-ANND-3	yes	17.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

25 targets.

Target	Regulation
AXIN2	Unknown
BCL2	Activation
BCL2L1	Activation
BIRC5	Activation
CCND1	Activation
CD1D	Activation
CD4	Activation
CEACAM5	Activation
CEACAM6	Activation
CEBPA	Repression
EPHB2	Activation
EPHB3	Activation
IFNG	Activation
IL17A	Activation
IL2	Activation
LEF1	Activation
MSLN	Activation
NT5E	Activation
PPARG	Activation
RUNX2	Activation
SNAI2	Unknown
TAGLN	Activation
TBXT
TPO	Repression
VEGFA	Activation

JASPAR motifs

Motif	Name	Family
MA0769.2	TCF7	TCF-7-related factors
MA0769.3	TCF7	TCF-7-related factors

JASPAR matrix evidence (PMIDs): PMID:28092692

Upstream regulators (CollecTRI, top): CTNNB1, NOTCH1, RBPJ, RUNX2, TCF7L2

miRNA regulators (miRDB)

70 targeting TCF7, 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-4692	100.00	67.32	2066
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749

Literature-anchored findings (GeneRIF, showing 40)

• beta-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 in colorectal cancer and along the crypt-villus axis. (PMID:12408869)
• A polymorphism in ths gene, C883A, is associated with type 1 diabetes. (PMID:12765974)
• Enforced expression of TCF-1 in transgenic mice yields an expanded Ly-49A subset of natural killer (NK) cells; TCF-1 regulates stable induction of Ly-49A gene expression by formation of a nucleoprotein complex at the Ly-49A promoter. (PMID:12847244)
• TCF1 is phosphorylated and inhibited by Wnt signal transduction through the Tak1 pathway (PMID:14960582)
• Ly-49A effectively limits Ag-driven T cell proliferation, cytokine production, and changes in surface receptor expression, and effectively limits Ag-specific CD4 cell responses even in the presence of sustained autoantigen expression in vivo (PMID:15778344)
• Involvement of transcription factor 7 (T cell factor-1) in the wingless type protein (WNT) signaling pathway not only regulates T cell development, but also peripheral T cell differentiation. (PMID:16424171)
• TCF7 is involved in genetic risk to Type I Diabetes, although the associations observed for both the intronic SNP rs17653687 and the nonsynonymous change encoded by rs5742913 are relatively modes. (PMID:19956102)
• Data show that upon HIPK2-mediated phosphorylation, TCF3 is replaced with positively acting TCF1 at a target promoter. (PMID:21285352)
• Transgenic T cell factor 1 (TCF1) binds to regulatory regions of the IL17 gene and directly regulates IL17A and IL17F gene expression. (PMID:21339363)
• Findings demonstrate that t-DARPP regulates beta-catenin/TCF activity, thereby implicating a novel oncogenic signaling in upper gastrointestinal cancers. (PMID:21447180)
• Results suggest that Tcf-1 may contribute to pathogenesis of acquired aplastic anemia by regulating downstream gene expression such as c-myc and CD44. (PMID:21881822)
• In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. [Review] (PMID:22111711)
• in this review, we will focus on the function of beta-catenin/TCF-1 pathway in the regulation of thymic and peripheral T cell differentiation processes–{REVIEW} (PMID:22535304)
• The repression of syndecan-2 by Wnt/beta-catenin/TCF signaling contributes to the resistance of osteosarcoma cells to doxorubicin. (PMID:22550000)
• findings show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces p21 expression and a stall in the growth of DLD1 colon cancer cells; results indicate that a rapid-response WNT/p21 circuit is driven by C-clamp target gene selection (PMID:22778133)
• Studied the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC). (PMID:23572277)
• we establish that ATF2 family members physically and functionally interact with TCF1/LEF1 factors to promote target gene expression and hematopoietic tumor cell growth (PMID:23966864)
• miRNAs inhibited the expression of the luciferase reporter constructs containing 3’UTRs of these genes and downregulated protein expression of TERT and the TCF7 transcription factor, which mediates the canonical Wnt pathway. (PMID:24551047)
• Results suggest ivermectin as therapeutic WNT protein-TCF transcription factor pathway response blocker to treat WNT-TCF-dependent diseases including multiple cancers. (PMID:25143352)
• we show that TCF7 is a direct target of miR-34a in prostate cancer that has metastasized to the bone (PMID:25436980)
• RUNX2 signaling pathways with their partners TCF7 and FGFR1/2 may not be involved in CCD pathogenesis (PMID:25738174)
• induction of expression activates the Wnt signaling pathway, leading to priming of liver cancer stem cells self-renewal and tumor propagation (PMID:25842979)
• Capsaicin-induced apoptosis in pancreatic cancer cells was associated with inhibition of beta-catenin signaling due to the dissociation of beta-catenin/TCF-1 complex and the process was orchestrated by STAT-3. (PMID:25869100)
• Findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties. (PMID:26079538)
• TCF7 plays critical roles in lung diseases [review] (PMID:26289446)
• Tcf7 levels are lower in islets taken from patients with type 2 diabetes. Knockdown of TCF7 in islets impairs the cytoprotective responsiveness to GIP and enhances the magnitude of apoptotic injury. (PMID:26642437)
• High expression of TCF7 is associated with osteosarcoma. (PMID:27683056)
• It promotes invasiveness and self-renewal of human non-small cell lung cancer cells. The potential role of lncTCF7 up regulation in NSCLC metastasis and suggest a promising potential to suppress lncTCF7 for NSCLC patients. (PMID:27766570)
• The results showed SNPs near TCF7 were associated with decreased expression of TCF7 mRNA in PBMCs from patients with SLE and suggested that the mRNA expression of the gene may be correlated with the pathogenesis of SLE. (PMID:28144936)
• Our study provides a new mechanism for chromatin occupancy of Tcf7 and uncovers the physiological significance of Uch37 during early vertebrate development by regulating the Wnt/beta-catenin pathway. (PMID:28198400)
• We demonstrated that the AR-miR-1 axis negatively regulates the novel oncogenic factor, TCF7. Dysregulation of TCF7 promoted a survival advantage and resistance to androgen deprivation, suggesting its therapeutic potential for castration-resistant prostate cancer. (PMID:28220803)
• LncRNATCF7 overexpression promoted the proliferation and migration of brain neoplasm glioma cells. (PMID:29091867)
• sSudy described a TCF7-dependent feedback control of the osteocalcin-GPRC6A axis in brown adipocyte physiologies. (PMID:29358218)
• High TCF7 expression associated with poor prognosis in Chinese glioblastoma multiforme patients. (PMID:29642232)
• Results demonstrated that TCF7 expression is upregulated by LOC728196 which operates as the sponge for miR-513c contributing to glioma cell growth and invasion by modulating. (PMID:30179681)
• Downregulation of lncTCF7 significantly inhibits migration and invasion of CRC cells by inhibiting TCF7 expression, suggesting that lncTCF7 may be a potential target for CRC therapy. (PMID:30225781)
• The expression of LEF1 associated positively with TCF1 (TCF7) and clinical progression of nasopharyngeal carcinoma, predicting poor prognosis. (PMID:30918012)
• The mRNA levels of TCF7 in GC tissues were significantly higher than in corresponding tumor adjacent tissues. The patients of low TCF7 expression and high TCF7 expression accounted for 76.79% (129/168) and 23.21% (39/168), respectively. (PMID:31133633)
• Postoperative detection of TCF7, c-Myc, and FOSL1 may be useful for stratifying patients with a high risk of unfavorable prognosis, and suppressing TCF7 or its downstream effectors may be a promising strategy for the treatment of Perihilar cholangiocarcinoma (PHCC) (PMID:31248836)
• Central memory CD8(+) T cells derive from stem-like Tcf7(hi) effector cells in the absence of cytotoxic differentiation. (PMID:33128876)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcf7	ENSDARG00000038672
mus_musculus	Tcf7	ENSMUSG00000000782
rattus_norvegicus	Tcf7	ENSRNOG00000005872

Paralogs (3): LEF1 (ENSG00000138795), TCF7L2 (ENSG00000148737), TCF7L1 (ENSG00000152284)

Protein

Protein identifiers

Transcription factor 7 — P36402 (reviewed: P36402)

Alternative names: T-cell-specific transcription factor 1

All UniProt accessions (12): P36402, B7WNT5, E5RG34, E5RG75, E5RGJ5, E5RGQ1, E5RHL1, E5RJ51, H0YAR8, H0YBC8, H0YBM1, H0YBP2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator involved in T-cell lymphocyte differentiation. Necessary for the survival of CD4(+) CD8(+) immature thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain cannot fulfill this role. Binds to the T-lymphocyte-specific enhancer element (5’-WWCAAAG-3’) found in the promoter of the CD3E gene. Represses expression of the T-cell receptor gamma gene in alpha-beta T-cell lineages. Required for the development of natural killer receptor-positive lymphoid tissue inducer T-cells. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and CTNNB1. May also act as feedback transcriptional repressor of CTNNB1 and TCF7L2 target genes.

Subunit / interactions. Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with TLE5, TLE1, TLE2, TLE3 and TLE4. Interacts with MLLT11. Long isoform interacts (via N-terminus) with SOX13; inhibits WNT-mediated transcriptional activity. Interacts with DAZAP2.

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in T-cells. Also detected in proliferating intestinal epithelial cells and in the basal epithelial cells of mammary gland epithelium.

Induction. By TCF7L2 and CTNNB1.

Similarity. Belongs to the TCF/LEF family.

Isoforms (15)

UniProt ID	Names	Canonical?
P36402-5	2L	yes
P36402-1	4L, D
P36402-2	4S, TCF-1A
P36402-3	1L
P36402-9	5L, D
P36402-10	5S, TCF-1D
P36402-13	7L, F
P36402-14	7S, TCF-1F
P36402-15	8L, G
P36402-16	8S, TCF-1G
P36402-6	2S, B, TCF-1B
P36402-7	3L
P36402-8	3S, C, TCF-1C
P36402-17	1S, TCF-1E
P36402-18	18

RefSeq proteins (8): NP_001128323, NP_001333354, NP_001333379, NP_001353431, NP_003193, NP_963963, NP_963965, NP_998813 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR013558	CTNNB1-bd_N	Domain
IPR024940	TCF/LEF	Family
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR036910	HMG_box_dom_sf	Homologous_superfamily

Pfam: PF00505, PF08347

UniProt features (22 total): splice variant 11, region of interest 4, compositionally biased region 3, chain 1, DNA-binding region 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36402-F1	58.11	0.18

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-4086398	Ca2+ pathway
R-HSA-4411364	Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-4641265	Repression of WNT target genes
R-HSA-8951430	RUNX3 regulates WNT signaling
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-9796292	Formation of axial mesoderm
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-212436	Generic Transcription Pathway
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9758941	Gastrulation
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 493 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, MORF_RAGE, FERRANDO_TAL1_NEIGHBORS, GOBP_REGULATION_OF_CELL_ACTIVATION, AP1_01, TSENG_IRS1_TARGETS_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, LFA1_Q6, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, GCANCTGNY_MYOD_Q6, MODULE_45

GO Biological Process (10): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), immune response (GO:0006955), gamma-delta T cell differentiation (GO:0042492), regulation of gamma-delta T cell differentiation (GO:0045586), canonical Wnt signaling pathway (GO:0060070), cellular response to interleukin-4 (GO:0071353), immune system process (GO:0002376), Wnt signaling pathway (GO:0016055), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity (GO:0001217), beta-catenin binding (GO:0008013), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), beta-catenin-TCF complex (GO:1990907)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signaling by WNT	3
TCF dependent signaling in response to WNT	2
Gastrulation	2
Beta-catenin independent WNT signaling	1
Formation of the beta-catenin:TCF transactivating complex	1
Degradation of beta-catenin by the destruction complex	1
Transcriptional regulation by RUNX3	1
MITF-M-dependent gene expression	1
Regulation of PD-L1(CD274) expression	1
Signal Transduction	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity	2
cellular anatomical structure	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
immune system process	1
response to stimulus	1
T cell differentiation	1
gamma-delta T cell activation	1
gamma-delta T cell differentiation	1
regulation of T cell differentiation	1
regulation of gamma-delta T cell activation	1
Wnt signaling pathway	1
response to interleukin-4	1
cellular response to cytokine stimulus	1
biological_process	1
cell surface receptor signaling pathway	1
negative regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
negative regulation of DNA-templated transcription	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

2578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCF7	CTNNB1	P35222	997
TCF7	AXIN2	Q9Y2T1	814
TCF7	SOX5	P35711	783
TCF7	HNF4A	P41235	778
TCF7	WNT3A	P56704	746
TCF7	AXIN1	O15169	728
TCF7	EOMES	O95936	682
TCF7	GSK3B	P49841	679
TCF7	TBX21	Q9UL17	668
TCF7	IL7R	P16871	666
TCF7	CTBP1	Q13363	665
TCF7	SP7	Q8TDD2	660
TCF7	BACH2	Q9BYV9	646
TCF7	CD8A	P01732	640
TCF7	CTBP2	P56545	638

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
CTNNB1	TCF7	psi-mi:“MI:0915”(physical association)	0.780
TCF7	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.780
TCF7	CTNNB1	psi-mi:“MI:0915”(physical association)	0.780
MLLT11	TCF7	psi-mi:“MI:0915”(physical association)	0.510
RUNX3	TCF7	psi-mi:“MI:0915”(physical association)	0.400
BCR	TCF7	psi-mi:“MI:0915”(physical association)	0.400
TCF7	SS18L1	psi-mi:“MI:0915”(physical association)	0.370
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
TCF7	RBFOX3	psi-mi:“MI:0914”(association)	0.350
BCL11B	CDK2AP1	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350
VSX1	NFIB	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (39): TCF7 (Affinity Capture-MS), TCF7 (Affinity Capture-MS), UCHL5 (Affinity Capture-Western), UCHL5 (Reconstituted Complex), TCF7 (Affinity Capture-Western), TCF7 (Biochemical Activity), TCF7 (Affinity Capture-Western), TCF7 (Affinity Capture-MS), TCF7 (Affinity Capture-MS), TCF7 (Affinity Capture-MS), USP21 (Affinity Capture-Western), TCF7 (Affinity Capture-Western), TCF7 (Proximity Label-MS), FN1 (Affinity Capture-MS), TOP2A (Affinity Capture-MS)

ESM2 similar proteins: A4IIJ8, A5A763, B7ZR65, F1LYL9, F1QQA8, O18896, O55170, P08151, P10070, P15207, P19091, P36402, P40646, P47806, P48434, P48436, P55878, P56693, P57073, P57074, P61753, P61754, P78411, Q00417, Q04886, Q04887, Q04888, Q28GC4, Q6DFF5, Q6F2E7, Q6IZ48, Q6VVD7, Q6XP49, Q7YRJ7, Q8AXX8, Q8CGW4, Q8K3Q3, Q90ZH7, Q96NZ1, Q9BG89

Diamond homologs: A0A0G2JTZ2, A2TED3, A8WWH5, B1H349, B3DM43, O94993, O95416, P27782, P35711, P35712, P36389, P36390, P36393, P36394, P36396, P36402, P40645, P40647, P40656, P57073, P57074, P61259, P70062, P70063, P70064, P91943, Q00417, Q03256, Q04886, Q04892, Q05738, Q10666, Q28447, Q2PG84, Q32PP9, Q5RCU4, Q62563, Q62565, Q67EX7, Q69FB1

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CTNNB1	up-regulates	TCF7	binding
TCF7	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
TCF7	“up-regulates quantity by expression”	VIM	“transcriptional regulation”
TCF7	“up-regulates quantity by expression”	SNAI1	“transcriptional regulation”
TCF7	“up-regulates quantity by expression”	FN1	“transcriptional regulation”
MLLT11	“up-regulates activity”	TCF7	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2112 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134115383:GGACG:G	donor_gain	1.0000
5:134115384:GACGG:G	donor_gain	1.0000
5:134115904:TCCA:T	acceptor_loss	1.0000
5:134115906:CA:C	acceptor_loss	1.0000
5:134115907:A:AG	acceptor_gain	1.0000
5:134115907:A:T	acceptor_loss	1.0000
5:134115908:G:GT	acceptor_gain	1.0000
5:134142305:G:GG	donor_gain	1.0000
5:134142711:T:TA	acceptor_gain	1.0000
5:134142715:CCTCA:C	acceptor_loss	1.0000
5:134142716:CTCA:C	acceptor_loss	1.0000
5:134142717:TCA:T	acceptor_loss	1.0000
5:134142719:A:AG	acceptor_gain	1.0000
5:134142719:A:G	acceptor_loss	1.0000
5:134142719:AG:A	acceptor_gain	1.0000
5:134142720:G:GA	acceptor_gain	1.0000
5:134142720:GG:G	acceptor_gain	1.0000
5:134142720:GGA:G	acceptor_gain	1.0000
5:134142720:GGAA:G	acceptor_gain	1.0000
5:134142849:A:T	donor_gain	1.0000
5:134142882:GG:G	donor_gain	1.0000
5:134142883:G:GT	donor_gain	1.0000
5:134142985:T:TA	acceptor_gain	1.0000
5:134142988:T:A	acceptor_gain	1.0000
5:134142988:TGCA:T	acceptor_loss	1.0000
5:134142989:GCA:G	acceptor_loss	1.0000
5:134142990:CA:C	acceptor_loss	1.0000
5:134142991:A:AG	acceptor_gain	1.0000
5:134142991:A:AT	acceptor_loss	1.0000
5:134142991:AGT:A	acceptor_gain	1.0000

AlphaMissense

2496 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002889 (5:134132755 G>A,C,T), RS1000005993 (5:134128273 T>A), RS1000030776 (5:134112306 T>C), RS1000100201 (5:134128496 G>A), RS1000100827 (5:134142445 G>C,T), RS1000188656 (5:134115246 AGC>A), RS1000267328 (5:134116805 T>C,G), RS1000295651 (5:134133620 C>T), RS1000304236 (5:134147666 G>A), RS1000315698 (5:134117113 C>G), RS1000422164 (5:134115093 G>A), RS1000429430 (5:134110154 G>A), RS1000512459 (5:134126511 C>T), RS1000556384 (5:134124557 G>A), RS1000598190 (5:134118319 C>T)

Disease associations

OMIM: gene MIM:189908 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001198_76	Multiple sclerosis	6.000000e-07
GCST002541_15	Menarche (age at onset)	3.000000e-20
GCST003155_48	Systemic lupus erythematosus	4.000000e-16
GCST003156_47	Systemic lupus erythematosus	7.000000e-10
GCST003622_50	Systemic lupus erythematosus	4.000000e-10
GCST004624_91	Sum eosinophil basophil counts	1.000000e-09
GCST005531_39	Multiple sclerosis	9.000000e-11
GCST005752_8	Systemic lupus erythematosus	7.000000e-07
GCST007932_38	Medication use (thyroid preparations)	6.000000e-16
GCST009597_315	Multiple sclerosis	3.000000e-14
GCST009724_49	Vertical cup-disc ratio (multi-trait analysis)	7.000000e-12
GCST009724_50	Vertical cup-disc ratio (multi-trait analysis)	5.000000e-14
GCST010571_29	Autoimmune thyroid disease	1.000000e-13
GCST010730_4	Rheumatoid arthritis	1.000000e-09
GCST011956_91	Systemic lupus erythematosus	4.000000e-14
GCST90002381_391	Eosinophil count	9.000000e-19
GCST90002382_124	Eosinophil percentage of white cells	2.000000e-16

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0009933	Thyroid preparation use measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3885542 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.36	Ki	440	nM	CHEMBL5189409
6.19	Ki	640	nM	CHEMBL4451478
5.52	IC50	3000	nM	CHEMBL5291202
5.52	IC50	3000	nM	CHEMBL2312139
5.50	IC50	3140	nM	CHEMBL5285142
5.26	IC50	5440	nM	CHEMBL5268653
5.22	IC50	6000	nM	CHEMBL1097925
5.00	IC50	1e+04	nM	CHEMBL5273461

PubChem BioAssay actives

8 with measured affinity, of 9 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(4S)-4-[[(2S)-2-[[(2S)-2-[(4-chloro-1H-indole-2-carbonyl)amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(2H-tetrazol-5-yl)propanoyl]amino]-5-oxo-5-[4-(trifluoromethoxy)anilino]pentanoic acid	1869134: Binding affinity to beta-catenin/Tcf (unknown origin) assessed as inhibition constant	ki	0.4400	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[(5-chloro-1H-indole-2-carbonyl)amino]-3-naphthalen-2-ylpropanoyl]amino]-3-(2H-tetrazol-5-yl)propanoyl]amino]-5-oxo-5-[4-(trifluoromethoxy)anilino]pentanoic acid	1869134: Binding affinity to beta-catenin/Tcf (unknown origin) assessed as inhibition constant	ki	0.6400	uM
(6S,9aS)-N-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide	1924299: Inhibition of beta catenin/TCF (unknown origin) by immunoprecipitation method	ic50	3.0000	uM
(6R,9aR)-N-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide	1923822: Inhibition of beta-catenin/TCF transcriptional activity in human SW480 cells by TOPFLASH reporter assay	ic50	3.0000	uM
1-methyl-5-[2-(2H-tetrazol-5-yl)ethyl]indazole	1923833: Inhibition of human beta-catenin (142 to 686 residues)/human TCF (7 to 51 residues) protein-protein interaction incubated for 3 hrs by fluorescence polarization assay	ic50	3.1400	uM
(3R)-16-(3,5-dimethoxyphenyl)-7,10-bis[(1S)-1-(4-methoxyphenyl)ethyl]-3-methyl-1-[2-(2-phenoxyphenyl)ethyl]-13-(3-propan-2-yloxypropyl)-1,4,7,10,13,16-hexazacyclooctadecane-2,5,8,11,14,17-hexone	1928063: Inhibition of N-terminal beta-catenin/full length myc-tagged TCF (unknown origin) trasfected in HEK293 cells measured for 48 hrs by	ic50	5.4400	uM
(2S)-2-[[(2S,4E)-4-[[(1R,2R,4aS,8aR)-2-methyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-hydroxymethylidene]-1-methyl-3,5-dioxopyrrolidin-2-yl]methyl]-2-hydroxy-3-methylbutanoic acid	477403: Inhibition of T cell factor7/beta-catenin interaction by protein fragment complementation assay	ic50	6.0000	uM
(19R)-13-(3,5-dimethoxyphenyl)-4,7-bis[(1R)-1-(4-methoxyphenyl)ethyl]-19-methyl-16-[2-(2-phenoxyphenyl)ethyl]-10-(3-propan-2-yloxypropyl)-1,4,7,10,13,16-hexazacyclononadecane-2,5,8,11,14,18-hexone	1924299: Inhibition of beta catenin/TCF (unknown origin) by immunoprecipitation method	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Lipopolysaccharides	increases expression, decreases reaction, decreases expression	2
Nickel	increases expression	2
Plant Extracts	affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
TL8-506	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
alpha-naphthoflavone	increases expression	1
quercitrin	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
tibolone	decreases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
naphthalene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
pentanal	increases expression	1
AH 23848	affects cotreatment, decreases expression	1
6-isopropoxy-9-oxoxanthene-2-carboxylic acid	affects cotreatment, decreases expression	1
homoorientin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1111854	Binding	Inhibition of T cell factor7/beta-catenin interaction by protein fragment complementation assay	JBIR-22, an inhibitor for protein-protein interaction of the homodimer of proteasome assembly factor 3. — J Nat Prod

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7E6	SEES3-1V human TCF7, clone1	Embryonic stem cell	Male
CVCL_A7E7	SEES3-1V human TCF7, clone2	Embryonic stem cell	Male
CVCL_A7E8	SEES3-1V human TCF7, clone3	Embryonic stem cell	Male
CVCL_B2IA	Abcam HeLa TCF7 KO	Cancer cell line	Female
CVCL_D8WX	Ubigene HCT 116 TCF7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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