Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription factor 12 (TCF12)
• Synonyms: TCF-12; Class B basic helix-loop-helix protein 20; bHLHb20; DNA-binding protein HTF4; E-box-binding protein; Transcription factor HTF-4
• Gene Name: TCF12
• Related Disease:
  Craniosynostosis 4
  TCF12-related craniosynostosis
  Trigonocephaly
  TWIST1-related craniosynostosis
  Acute lymphocytic leukaemia
  Adult teratoma
  Advanced cancer
  Brain cancer
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Hypogonadotropic hypogonadism 26 with or without anosmia
  Intellectual disability
  Kallmann syndrome
  Neoplasm
  Neuralgia
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Saethre-Chotzen syndrome
  Stomach cancer
  Syndactyly
  Synostosis
  Teratoma
  Obsolete isolated brachycephaly
  Obsolete isolated plagiocephaly
  Alopecia
  Bone osteosarcoma
  Craniosynostosis
  Gallbladder cancer
  Gallbladder carcinoma
  Head and neck carcinoma
  Hypertrichosis
  Meningioma
  Meningitis
  Osteosarcoma
  Periodontitis
• UniProt ID: HTF4_HUMAN
• PDB ID: 2KNH; 4JOL
• Pfam ID: PF00010
• Sequence:
  MNPQQQRMAAIGTDKELSDLLDFSAMFSPPVNSGKTRPTTLGSSQFSGSGIDERGGTTSW
  GTSGQPSPSYDSSRGFTDSPHYSDHLNDSRLGAHEGLSPTPFMNSNLMGKTSERGSFSLY
  SRDTGLPGCQSSLLRQDLGLGSPAQLSSSGKPGTAYYSFSATSSRRRPLHDSAALDPLQA
  KKVRKVPPGLPSSVYAPSPNSDDFNRESPSYPSPKPPTSMFASTFFMQDGTHNSSDLWSS
  SNGMSQPGFGGILGTSTSHMSQSSSYGNLHSHDRLSYPPHSVSPTDINTSLPPMSSFHRG
  STSSSPYVAASHTPPINGSDSILGTRGNAAGSSQTGDALGKALASIYSPDHTSSSFPSNP
  STPVGSPSPLTGTSQWPRPGGQAPSSPSYENSLHSLQSRMEDRLDRLDDAIHVLRNHAVG
  PSTSLPAGHSDIHSLLGPSHNAPIGSLNSNYGGSSLVASSRSASMVGTHREDSVSLNGNH
  SVLSSTVTTSSTDLNHKTQENYRGGLQSQSGTVVTTEIKTENKEKDENLHEPPSSDDMKS
  DDESSQKDIKVSSRGRTSSTNEDEDLNPEQKIEREKERRMANNARERLRVRDINEAFKEL
  GRMCQLHLKSEKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRREEEKVSAVSAE
  PPTTLPGTHPGLSETTNPMGHM
• Function: Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). May be involved in the functional network that regulates the development of the GnRH axis.
• Tissue Specificity: Expressed in several tissues and cell types including skeletal muscle, thymus, and a B-cell line.
• Reactome Pathway:
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  NGF-stimulated transcription (R-HSA-9031628)
  Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis 4	DISZX1GK	Definitive	Biomarker	[1]
TCF12-related craniosynostosis	DIS06KE9	Definitive	Autosomal dominant	[2]
Trigonocephaly	DISHV6BA	Definitive	Biomarker	[1]
TWIST1-related craniosynostosis	DISGRP2G	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Adult teratoma	DISBY81U	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Brain cancer	DISBKFB7	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Hypogonadotropic hypogonadism 26 with or without anosmia	DISOM7UR	Strong	Autosomal dominant	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[13]
Kallmann syndrome	DISO3HDG	Strong	Autosomal recessive	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Neuralgia	DISWO58J	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Saethre-Chotzen syndrome	DIS3A437	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Syndactyly	DISZK2BT	Strong	Genetic Variation	[19]
Synostosis	DISXGMZW	Strong	Genetic Variation	[20]
Teratoma	DIS6ICY4	Strong	Altered Expression	[4]
Obsolete isolated brachycephaly	DIS39ZDS	Supportive	Autosomal dominant	[1]
Obsolete isolated plagiocephaly	DISSZTKC	Supportive	Autosomal dominant	[1]
Alopecia	DIS37HU4	Limited	Genetic Variation	[21]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[22]
Craniosynostosis	DIS6J405	Limited	Biomarker	[18]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[23]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[23]
Head and neck carcinoma	DISOU1DS	Limited	Altered Expression	[24]
Hypertrichosis	DISZUK5W	Limited	Biomarker	[25]
Meningioma	DISPT4TG	Limited	Biomarker	[26]
Meningitis	DISQABAA	Limited	Biomarker	[27]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[22]
Periodontitis	DISI9JOI	Limited	Genetic Variation	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transcription factor 12 (TCF12).	[29]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transcription factor 12 (TCF12).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transcription factor 12 (TCF12).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor 12 (TCF12).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transcription factor 12 (TCF12).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription factor 12 (TCF12).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor 12 (TCF12).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor 12 (TCF12).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor 12 (TCF12).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor 12 (TCF12).	[34]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor 12 (TCF12).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor 12 (TCF12).	[31]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Transcription factor 12 (TCF12).	[37]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Transcription factor 12 (TCF12).	[38]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Transcription factor 12 (TCF12).	[39]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Transcription factor 12 (TCF12).	[40]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Transcription factor 12 (TCF12).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor 12 (TCF12).	[42]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transcription factor 12 (TCF12).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor 12 (TCF12).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor 12 (TCF12).	[47]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Transcription factor 12 (TCF12).	[48]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Transcription factor 12 (TCF12).	[41]

References

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