Details of Drug Off-Target (DOT)

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

• DOT Name: TFIIA-alpha and beta-like factor (GTF2A1L)
• Synonyms: General transcription factor II A, 1-like factor
• Gene Name: GTF2A1L
• Related Disease:
  Acute leukaemia
  Acute liver failure
  Azoospermia
  Coagulation defect
  Epilepsy
  FRAXE intellectual disability
  Hepatitis B virus infection
  Hepatitis C virus infection
  Herpes simplex infection
  Neoplasm
  Oligospermia
  Wilson disease
  Adrenoleukodystrophy
  Hepatitis
• UniProt ID: TF2AY_HUMAN
• Pfam ID: PF03153
• Sequence:
  MACLNPVPKLYRSVIEDVIEGVRNLFAEEGIEEQVLKDLKQLWETKVLQSKATEDFFRNS
  IQSPLFTLQLPHSLHQTLQSSTASLVIPAGRTLPSFTTAELGTSNSSANFTFPGYPIHVP
  AGVTLQTVSGHLYKVNVPIMVTETSGRAGILQHPIQQVFQQLGQPSVIQTSVPQLNPWSL
  QATTEKSQRIETVLQQPAILPSGPVDRKHLENATSDILVSPGNEHKIVPEALLCHQESSH
  YISLPGVVFSPQVSQTNSNVESVLSGSASMAQNLHDESLSTSPHGALHQHVTDIQLHILK
  NRMYGCDSVKQPRNIEEPSNIPVSEKDSNSQVDLSIRVTDDDIGEIIQVDGSGDTSSNEE
  IGSTRDADENEFLGNIDGGDLKVPEEEADSISNEDSATNSSDNEDPQVNIVEEDPLNSGD
  DVSEQDVPDLFDTDNVIVCQYDKIHRSKNKWKFYLKDGVMCFGGRDYVFAKAIGDAEW
• Function: May function as a testis specific transcription factor. Binds DNA in conjunction with GTF2A2 and TBP (the TATA-binding protein) and together with GTF2A2, allows mRNA transcription.
• Tissue Specificity: Testis specific. Detected in adult testis mostly in round and elongating spermatids (at protein level). Detected in testis.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Viral carcinogenesis (hsa05203)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[1]
Acute liver failure	DIS5EZKX	Strong	Biomarker	[2]
Azoospermia	DIS94181	Strong	Genetic Variation	[3]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
FRAXE intellectual disability	DISDPS6G	Strong	Genetic Variation	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[7]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[10]
Wilson disease	DISVS9H7	Strong	Biomarker	[2]
Adrenoleukodystrophy	DISTUD1F	moderate	Biomarker	[11]
Hepatitis	DISXXX35	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of TFIIA-alpha and beta-like factor (GTF2A1L).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TFIIA-alpha and beta-like factor (GTF2A1L).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of TFIIA-alpha and beta-like factor (GTF2A1L).	[15]

References

• [1] The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling.Hum Mol Genet. 2007 Jan 1;16(1):92-106. doi: 10.1093/hmg/ddl444. Epub 2006 Nov 29.
• [2] Plasmapheresis Combined with Continuous Plasma Filtration Adsorption Rescues Severe Acute Liver Failure in Wilson's Disease before Liver Transplantation.Blood Purif. 2019;47(1-3):120-125. doi: 10.1159/000493909. Epub 2018 Oct 25.
• [3] Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3 genes with non-obstructive azoospermia in the Chinese population.J Assist Reprod Genet. 2015 Jan;32(1):95-101. doi: 10.1007/s10815-014-0369-y. Epub 2014 Nov 6.
• [4] Bleeding complications in acute liver failure.Hepatology. 2018 May;67(5):1931-1942. doi: 10.1002/hep.29694. Epub 2018 Mar 26.
• [5] Accelerated long-term forgetting and behavioural difficulties in children with epilepsy.Cortex. 2019 Jan;110:92-100. doi: 10.1016/j.cortex.2018.03.021. Epub 2018 Mar 30.
• [6] Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels.Hepatology. 2012 Mar;55(3):676-84. doi: 10.1002/hep.24732. Epub 2012 Jan 31.
• [7] Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.J Infect Dis. 2004 Jan 1;189(1):7-14. doi: 10.1086/380202. Epub 2003 Dec 31.
• [8] Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection.Pediatr Transplant. 2017 Nov;21(7). doi: 10.1111/petr.13021. Epub 2017 Jul 23.
• [9] Identification of a sodium pump Na(+)/K(+) ATPase 1-targeted peptide for PET imaging of breast cancer.J Control Release. 2018 Jul 10;281:178-188. doi: 10.1016/j.jconrel.2018.05.019. Epub 2018 May 17.
• [10] Aberrant methylation of the TDMR of the GTF2A1L promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis.Asian J Androl. 2013 Sep;15(5):634-9. doi: 10.1038/aja.2013.56. Epub 2013 Jun 17.
• [11] Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.Gut Liver. 2017 Mar 15;11(2):173-188. doi: 10.5009/gnl16477.
• [12] The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure.Front Immunol. 2018 Dec 14;9:2948. doi: 10.3389/fimmu.2018.02948. eCollection 2018.
• [13] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [14] Transcription Factor IIA tau is associated with undifferentiated cells and its gene expression is repressed in primary neurons at the chromatin level in vivo. Stem Cells Dev. 2006 Apr;15(2):175-90. doi: 10.1089/scd.2006.15.175.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.