Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ID822)

• DOT Name: Transcription factor 7 (TCF7)
• Synonyms: TCF-7; T-cell-specific transcription factor 1; T-cell factor 1; TCF-1
• Gene Name: TCF7
• Related Disease:
  Acute lymphocytic leukaemia
  Adenoma
  Advanced cancer
  Astrocytoma
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Crohn disease
  Diabetic kidney disease
  Esophageal squamous cell carcinoma
  Fatty liver disease
  Glioblastoma multiforme
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Matthew-Wood syndrome
  Maturity-onset diabetes of the young
  Maturity-onset diabetes of the young type 3
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  T-cell acute lymphoblastic leukaemia
  Type-1 diabetes
  Ulcerative colitis
  Neuroblastoma
  Small lymphocytic lymphoma
  Gastric cancer
  Stomach cancer
  Asthma
  Autoimmune disease
  Colorectal neoplasm
  Systemic lupus erythematosus
• UniProt ID: TCF7_HUMAN
• Pfam ID: PF08347 ; PF00505
• Sequence:
  MPQLDSGGGGAGGGDDLGAPDELLAFQDEGEEQDDKSRDSAAGPERDLAELKSSLVNESE
  GAAGGAGIPGVPGAGAGARGEAEALGREHAAQRLFPDKLPEPLEDGLKAPECTSGMYKET
  VYSAFNLLMHYPPPSGAGQHPQPQPPLHKANQPPHGVPQLSLYEHFNSPHPTPAPADISQ
  KQVHRPLQTPDLSGFYSLTSGSMGQLPHTVSWFTHPSLMLGSGVPGHPAAIPHPAIVPPS
  GKQELQPFDRNLKTQAESKAEKEAKKPTIKKPLNAFMLYMKEMRAKVIAECTLKESAAIN
  QILGRRWHALSREEQAKYYELARKERQLHMQLYPGWSARDNYGKKKRRSREKHQESTTET
  NWPRELKDGNGQESLSMSSSSSPA
• 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.
• Tissue Specificity: Predominantly expressed in T-cells. Also detected in proliferating intestinal epithelial cells and in the basal epithelial cells of mammary gland epithelium.
• KEGG Pathway:
  Wnt sig.ling pathway (hsa04310)
  Hippo sig.ling pathway (hsa04390)
  Adherens junction (hsa04520)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Melanogenesis (hsa04916)
  Cushing syndrome (hsa04934)
  Alcoholic liver disease (hsa04936)
  Salmonella infection (hsa05132)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Pathways in cancer (hsa05200)
  Colorectal cancer (hsa05210)
  Endometrial cancer (hsa05213)
  Prostate cancer (hsa05215)
  Thyroid cancer (hsa05216)
  Basal cell carcinoma (hsa05217)
  Acute myeloid leukemia (hsa05221)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
• Reactome Pathway:
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Ca2+ pathway (R-HSA-4086398)
  Binding of TCF/LEF (R-HSA-4411364)
  Repression of WNT target genes (R-HSA-4641265)
  RUNX3 regulates WNT signaling (R-HSA-8951430)
  Germ layer formation at gastrulation (R-HSA-9754189)
  Formation of axial mesoderm (R-HSA-9796292)
  Formation of the beta-catenin (R-HSA-201722)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[4]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[9]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[13]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[16]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[17]
Maturity-onset diabetes of the young	DISG75M5	Strong	Genetic Variation	[18]
Maturity-onset diabetes of the young type 3	DISMFSO5	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[22]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Altered Expression	[23]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[24]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[25]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[26]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[27]
Gastric cancer	DISXGOUK	Disputed	Altered Expression	[28]
Stomach cancer	DISKIJSX	Disputed	Altered Expression	[28]
Asthma	DISW9QNS	Limited	Biomarker	[29]
Autoimmune disease	DISORMTM	Limited	Biomarker	[30]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[31]
Systemic lupus erythematosus	DISI1SZ7	Limited	Altered Expression	[32]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transcription factor 7 (TCF7).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor 7 (TCF7).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor 7 (TCF7).	[35]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription factor 7 (TCF7).	[36]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor 7 (TCF7).	[37]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor 7 (TCF7).	[33]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Transcription factor 7 (TCF7).	[38]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transcription factor 7 (TCF7).	[39]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Transcription factor 7 (TCF7).	[40]
Tibolone	DM78XFG	Approved	Tibolone decreases the expression of Transcription factor 7 (TCF7).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor 7 (TCF7).	[42]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transcription factor 7 (TCF7).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor 7 (TCF7).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor 7 (TCF7).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor 7 (TCF7).	[46]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transcription factor 7 (TCF7).	[47]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Transcription factor 7 (TCF7).	[48]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Transcription factor 7 (TCF7).	[49]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Transcription factor 7 (TCF7).	[50]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of Transcription factor 7 (TCF7).	[50]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Transcription factor 7 (TCF7).	[51]

References

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