Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8LQAOV)

• DOT Name: Transcription factor 20 (TCF20)
• Synonyms: TCF-20; Nuclear factor SPBP; Protein AR1; Stromelysin-1 PDGF-responsive element-binding protein; SPRE-binding protein
• Gene Name: TCF20
• Related Disease:
  Developmental delay with variable intellectual impairment and behavioral abnormalities
  Autism spectrum disorder
  Desmoid tumour
  Intellectual disability
  Movement disorder
  Pervasive developmental disorder
  Potocki-Lupski syndrome
  Smith-Magenis syndrome
  Syndromic intellectual disability
  Overgrowth syndrome
  Schizophrenia
• UniProt ID: TCF20_HUMAN
• Pfam ID: PF13771
• Sequence:
  MQSFREQSSYHGNQQSYPQEVHGSSRLEEFSPRQAQMFQNFGGTGGSSGSSGSGSGGGRR
  GAAAAAAAMASETSGHQGYQGFRKEAGDFYYMAGNKDPVTTGTPQPPQRRPSGPVQSYGP
  PQGSSFGNQYGSEGHVGQFQAQHSGLGGVSHYQQDYTGPFSPGSAQYQQQASSQQQQQQV
  QQLRQQLYQSHQPLPQATGQPASSSSHLQPMQRPSTLPSSAAGYQLRVGQFGQHYQSSAS
  SSSSSSFPSPQRFSQSGQSYDGSYNVNAGSQYEGHNVGSNAQAYGTQSNYSYQPQSMKNF
  EQAKIPQGTQQGQQQQQPQQQQHPSQHVMQYTNAATKLPLQSQVGQYNQPEVPVRSPMQF
  HQNFSPISNPSPAASVVQSPSCSSTPSPLMQTGENLQCGQGSVPMGSRNRILQLMPQLSP
  TPSMMPSPNSHAAGFKGFGLEGVPEKRLTDPGLSSLSALSTQVANLPNTVQHMLLSDALT
  PQKKTSKRPSSSKKADSCTNSEGSSQPEEQLKSPMAESLDGGCSSSSEDQGERVRQLSGQ
  STSSDTTYKGGASEKAGSSPAQGAQNEPPRLNASPAAREEATSPGAKDMPLSSDGNPKVN
  EKTVGVIVSREAMTGRVEKPGGQDKGSQEDDPAATQRPPSNGGAKETSHASLPQPEPPGG
  GGSKGNKNGDNNSNHNGEGNGQSGHSAAGPGFTSRTEPSKSPGSLRYSYKDSFGSAVPRN
  VSGFPQYPTGQEKGDFTGHGERKGRNEKFPSLLQEVLQGYHHHPDRRYSRSTQEHQGMAG
  SLEGTTRPNVLVSQTNELASRGLLNKSIGSLLENPHWGPWERKSSSTAPEMKQINLTDYP
  IPRKFEIEPQSSAHEPGGSLSERRSVICDISPLRQIVRDPGAHSLGHMSADTRIGRNDRL
  NPTLSQSVILPGGLVSMETKLKSQSGQIKEEDFEQSKSQASFNNKKSGDHCHPPSIKHES
  YRGNASPGAATHDSLSDYGPQDSRPTPMRRVPGRVGGREGMRGRSPSQYHDFAEKLKMSP
  GRSRGPGGDPHHMNPHMTFSERANRSSLHTPFSPNSETLASAYHANTRAHAYGDPNAGLN
  SQLHYKRQMYQQQPEEYKDWSSGSAQGVIAAAQHRQEGPRKSPRQQQFLDRVRSPLKNDK
  DGMMYGPPVGTYHDPSAQEAGRCLMSSDGLPNKGMELKHGSQKLQESCWDLSRQTSPAKS
  SGPPGMSSQKRYGPPHETDGHGLAEATQSSKPGSVMLRLPGQEDHSSQNPLIMRRRVRSF
  ISPIPSKRQSQDVKNSSTEDKGRLLHSSKEGADKAFNSYAHLSHSQDIKSIPKRDSSKDL
  PSPDSRNCPAVTLTSPAKTKILPPRKGRGLKLEAIVQKITSPNIRRSASSNSAEAGGDTV
  TLDDILSLKSGPPEGGSVAVQDADIEKRKGEVASDLVSPANQELHVEKPLPRSSEEWRGS
  VDDKVKTETHAETVTAGKEPPGAMTSTTSQKPGSNQGRPDGSLGGTAPLIFPDSKNVPPV
  GILAPEANPKAEEKENDTVTISPKQEGFPPKGYFPSGKKKGRPIGSVNKQKKQQQPPPPP
  PQPPQIPEGSADGEPKPKKQRQRRERRKPGAQPRKRKTKQAVPIVEPQEPEIKLKYATQP
  LDKTDAKNKSFYPYIHVVNKCELGAVCTIINAEEEEQTKLVRGRKGQRSLTPPPSSTESK
  ALPASSFMLQGPVVTESSVMGHLVCCLCGKWASYRNMGDLFGPFYPQDYAATLPKNPPPK
  RATEMQSKVKVRHKSASNGSKTDTEEEEEQQQQQKEQRSLAAHPRFKRRHRSEDCGGGPR
  SLSRGLPCKKAATEGSSEKTVLDSKPSVPTTSEGGPELELQIPELPLDSNEFWVHEGCIL
  WANGIYLVCGRLYGLQEALEIAREMKCSHCQEAGATLGCYNKGCSFRYHYPCAIDADCLL
  HEENFSVRCPKHKPPLPCPLPPLQNKTAKGSLSTEQSERG
• Function: Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator.
• Tissue Specificity: Expressed in most tissues, except in ovary and prostate. Isoform 1 is exclusively expressed in brain, heart and testis, and this form predominates in liver and kidney. Isoform 2 predominates in lung.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental delay with variable intellectual impairment and behavioral abnormalities	DISP2L6M	Definitive	Autosomal dominant	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Desmoid tumour	DISGX357	Strong	Altered Expression	[3]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[4]
Movement disorder	DISOJJ2D	Strong	CausalMutation	[5]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[6]
Potocki-Lupski syndrome	DISUOI38	Strong	Genetic Variation	[4]
Smith-Magenis syndrome	DISG4G6X	Strong	Biomarker	[4]
Syndromic intellectual disability	DISH7SDF	Supportive	Autosomal dominant	[7]
Overgrowth syndrome	DISHK54G	Limited	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Transcription factor 20 (TCF20) affects the response to substance of Acetaminophen.	[18]

3 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 20 (TCF20).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Transcription factor 20 (TCF20).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transcription factor 20 (TCF20).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor 20 (TCF20).	[10]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Transcription factor 20 (TCF20).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor 20 (TCF20).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transcription factor 20 (TCF20).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor 20 (TCF20).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription factor 20 (TCF20).	[17]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] De novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth.Eur J Hum Genet. 2016 Dec;24(12):1739-1745. doi: 10.1038/ejhg.2016.90. Epub 2016 Jul 20.
• [3] A gene expression signature that distinguishes desmoid tumours from nodular fasciitis.J Pathol. 2006 Mar;208(4):543-53. doi: 10.1002/path.1915.
• [4] De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome.Genome Med. 2019 Feb 28;11(1):12. doi: 10.1186/s13073-019-0623-0.
• [5] Prevalence and architecture of de novo mutations in developmental disorders. Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.
• [6] De novo and rare inherited mutations implicate the transcriptional coregulator TCF20/SPBP in autism spectrum disorder. J Med Genet. 2014 Nov;51(11):737-47. doi: 10.1136/jmedgenet-2014-102582. Epub 2014 Sep 16.
• [7] Correction to: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. Genome Med. 2019 Mar 25;11(1):16. doi: 10.1186/s13073-019-0630-1.
• [8] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.