Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB9ASTK)

• DOT Name: Transcription factor 4 (TCF4)
• Synonyms: TCF-4; Class B basic helix-loop-helix protein 19; bHLHb19; Immunoglobulin transcription factor 2; ITF-2; SL3-3 enhancer factor 2; SEF-2
• Gene Name: TCF4
• Related Disease:
  Pitt-Hopkins syndrome
  Prostate carcinoma
  Advanced cancer
  Attention deficit hyperactivity disorder
  Breast cancer
  Breast carcinoma
  Cardiac disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Corneal dystrophy, Fuchs endothelial, 1
  Corneal dystrophy, Fuchs endothelial, 3
  Cryptorchidism
  Depression
  Dysautonomia
  Endometrial carcinoma
  Familial adenomatous polyposis
  Familial prostate carcinoma
  Fleck corneal dystrophy
  Glioma
  Inflammatory bowel disease
  Isolated congenital microcephaly
  Lung cancer
  Major depressive disorder
  Mental disorder
  Mood disorder
  Neurodevelopmental disorder
  Osteoarthritis
  Prostate cancer, hereditary, 1
  Psychotic disorder
  Sclerosing cholangitis
  Stomach cancer
  Ulcerative colitis
  Hirschsprung disease
  Movement disorder
  Non-insulin dependent diabetes
  Primary sclerosing cholangitis
  Autosomal dominant non-syndromic intellectual disability
  Fuchs' endothelial dystrophy
  Liver cancer
  Microlissencephaly
  Alopecia
  Autism spectrum disorder
  Crohn disease
  Intellectual disability
  leukaemia
  Leukemia
  Lung carcinoma
  Neoplasm
• UniProt ID: ITF2_HUMAN
• PDB ID: 2KWF; 6OD3; 6OD4; 6OD5
• Pfam ID: PF00010
• Sequence:
  MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLASGHFTGSNVEDRSSSGSWG
  NGGHPSPSRNYGDGTPYDHMTSRDLGSHDNLSPPFVNSRIQSKTERGSYSSYGRESNLQG
  CHQQSLLGGDMDMGNPGTLSPTKPGSQYYQYSSNNPRRRPLHSSAMEVQTKKVRKVPPGL
  PSSVYAPSASTADYNRDSPGYPSSKPATSTFPSSFFMQDGHHSSDPWSSSSGMNQPGYAG
  MLGNSSHIPQSSSYCSLHPHERLSYPSHSSADINSSLPPMSTFHRSGTNHYSTSSCTPPA
  NGTDSIMANRGSGAAGSSQTGDALGKALASIYSPDHTNNSFSSNPSTPVGSPPSLSAGTA
  VWSRNGGQASSSPNYEGPLHSLQSRIEDRLERLDDAIHVLRNHAVGPSTAMPGGHGDMHG
  IIGPSHNGAMGGLGSGYGTGLLSANRHSLMVGTHREDGVALRGSHSLLPNQVPVPQLPVQ
  SATSPDLNPPQDPYRGMPPGLQGQSVSSGSSEIKSDDEGDENLQDTKSSEDKKLDDDKKD
  IKSITSNNDDEDLTPEQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKP
  QTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRREEEKVSSEPPPLSLAGPHPGMGDA
  SNHMGQM
• Function: Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription. Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'.
• Tissue Specificity: Expressed in adult heart, brain, placenta, skeletal muscle and to a lesser extent in the lung. In developing embryonic tissues, expression mostly occurs in the brain.
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pitt-Hopkins syndrome	DISM1JID	Definitive	Autosomal dominant	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cardiac disease	DISVO1I5	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[10]
Corneal dystrophy, Fuchs endothelial, 1	DISOQIO0	Strong	Biomarker	[11]
Corneal dystrophy, Fuchs endothelial, 3	DISAQYUB	Strong	Autosomal dominant	[12]
Cryptorchidism	DISYUD2P	Strong	Genetic Variation	[13]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Dysautonomia	DISF4MT6	Strong	Genetic Variation	[15]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[16]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[17]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[18]
Fleck corneal dystrophy	DISERQJ1	Strong	Genetic Variation	[19]
Glioma	DIS5RPEH	Strong	Biomarker	[20]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[21]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[22]
Lung cancer	DISCM4YA	Strong	Altered Expression	[23]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[24]
Mental disorder	DIS3J5R8	Strong	Biomarker	[25]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[26]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[27]
Osteoarthritis	DIS05URM	Strong	Biomarker	[28]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[18]
Psychotic disorder	DIS4UQOT	Strong	Genetic Variation	[29]
Sclerosing cholangitis	DIS7GZNB	Strong	Genetic Variation	[30]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[31]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[30]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[32]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[33]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Biomarker	[34]
Primary sclerosing cholangitis	DISTH5WJ	moderate	Genetic Variation	[35]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[36]
Fuchs' endothelial dystrophy	DISL7TXC	Supportive	Autosomal dominant	[37]
Liver cancer	DISDE4BI	Disputed	Biomarker	[38]
Microlissencephaly	DISUCKNT	Disputed	Biomarker	[22]
Alopecia	DIS37HU4	Limited	Genetic Variation	[39]
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[40]
Crohn disease	DIS2C5Q8	Limited	Altered Expression	[41]
Intellectual disability	DISMBNXP	Limited	Autosomal dominant	[40]
leukaemia	DISS7D1V	Limited	Biomarker	[42]
Leukemia	DISNAKFL	Limited	Biomarker	[42]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[43]
Neoplasm	DISZKGEW	Limited	Biomarker	[27]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Transcription factor 4 (TCF4).	[44]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Transcription factor 4 (TCF4).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor 4 (TCF4).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor 4 (TCF4).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor 4 (TCF4).	[45]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor 4 (TCF4).	[46]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor 4 (TCF4).	[47]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Transcription factor 4 (TCF4).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription factor 4 (TCF4).	[49]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription factor 4 (TCF4).	[50]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription factor 4 (TCF4).	[51]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Transcription factor 4 (TCF4).	[53]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transcription factor 4 (TCF4).	[54]
Aspirin	DM672AH	Approved	Aspirin decreases the activity of Transcription factor 4 (TCF4).	[55]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate increases the expression of Transcription factor 4 (TCF4).	[56]
Sulindac	DM2QHZU	Approved	Sulindac decreases the activity of Transcription factor 4 (TCF4).	[55]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Transcription factor 4 (TCF4).	[57]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcription factor 4 (TCF4).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transcription factor 4 (TCF4).	[59]
NCX-4016	DMOX1CU	Phase 2	NCX-4016 affects the expression of Transcription factor 4 (TCF4).	[60]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor 4 (TCF4).	[62]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transcription factor 4 (TCF4).	[63]
Calphostin C	DM9X2D0	Terminated	Calphostin C increases the expression of Transcription factor 4 (TCF4).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Transcription factor 4 (TCF4).	[65]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Transcription factor 4 (TCF4).	[66]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Transcription factor 4 (TCF4).	[67]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor 4 (TCF4).	[68]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Transcription factor 4 (TCF4).	[69]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Transcription factor 4 (TCF4).	[70]

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