Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGKS24X)

• DOT Name: Thioredoxin-like protein 4A
• Synonyms: DIM1 protein homolog; Spliceosomal U5 snRNP-specific 15 kDa protein; Thioredoxin-like U5 snRNP protein U5-15kD
• Gene Name: TXNL4A
• Related Disease: Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome
• UniProt ID: TXN4A_HUMAN
• PDB ID: 1PQN; 1QGV; 1SYX; 3JCR; 4BWQ; 4BWS; 4CDO; 5O9Z; 6AH0; 6AHD; 6QW6; 6QX9
• Pfam ID: PF02966
• Sequence:
  MSYMLPHLHNGWQVDQAILSEEDRVVVIRFGHDWDPTCMKMDEVLYSIAEKVKNFAVIYL
  VDITEVPDFNKMYELYDPCTVMFFFRNKHIMIDLGTGNNNKINWAMEDKQEMVDIIETVY
  RGARKGRGLVVSPKDYSTKYRY
• Function: Plays a role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes that are involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	DISI9JIG	Definitive	Autosomal recessive	[1]

5 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 Thioredoxin-like protein 4A.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thioredoxin-like protein 4A.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Thioredoxin-like protein 4A.	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thioredoxin-like protein 4A.	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thioredoxin-like protein 4A.	[7]

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 affects the methylation of Thioredoxin-like protein 4A.	[6]

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] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.