Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXRDF3Z)

• DOT Name: Adenosine deaminase domain-containing protein 1 (ADAD1)
• Synonyms: Testis nuclear RNA-binding protein
• Gene Name: ADAD1
• Related Disease:
  Advanced cancer
  Coeliac disease
  Rheumatoid arthritis
  Type-1 diabetes
  Ulcerative colitis
• UniProt ID: ADAD1_HUMAN
• Pfam ID: PF02137 ; PF00035
• Sequence:
  MASNNHWFQSSQVPSFAQMLKKNLPVQPATKTITTPTGWSSESYGLSKMASKVTQVTGNF
  PEPLLSKNLSSISNPVLPPKKIPKEFIMKYKRGEINPVSALHQFAQMQRVQLDLKETVTT
  GNVMGPYFAFCAVVDGIQYKTGLGQNKKESRSNAAKLALDELLQLDEPEPRILETSGPPP
  FPAEPVVLSELAYVSKVHYEGRHIQYAKISQIVKERFNQLISNRSEYLKYSSSLAAFIIE
  RAGQHEVVAIGTGEYNYSQDIKPDGRVLHDTHAVVTARRSLLRYFYRQLLLFYSKNPAMM
  EKSIFCTEPTSNLLTLKQNINICLYMNQLPKGSAQIKSQLRLNPHSISAFEANEELCLHV
  AVEGKIYLTVYCPKDGVNRISSMSSSDKLTRWEVLGVQGALLSHFIQPVYISSILIGDGN
  CSDTRGLEIAIKQRVDDALTSKLPMFYLVNRPHISLVPSAYPLQMNLEYKFLSLNWAQGD
  VSLEIVDGLSGKITESSPFKSGMSMASRLCKAAMLSRFNLLAKEAKKELLEAGTYHAAKC
  MSASYQEAKCKLKSYLQQHGYGSWIVKSPCIEQFNM
• Function: Required for male fertility and normal male germ cell differentiation. Plays a role in spermatogenesis. Binds to RNA but not to DNA.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[3]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[4]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[5]

2 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 Adenosine deaminase domain-containing protein 1 (ADAD1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Adenosine deaminase domain-containing protein 1 (ADAD1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenosine deaminase domain-containing protein 1 (ADAD1).	[8]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Adenosine deaminase domain-containing protein 1 (ADAD1).	[9]

References

• [1] Cancer risk susceptibility loci in a Swedish population.Oncotarget. 2017 Nov 25;8(66):110300-110310. doi: 10.18632/oncotarget.22687. eCollection 2017 Dec 15.
• [2] A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.Nat Genet. 2007 Jul;39(7):827-9. doi: 10.1038/ng2058. Epub 2007 Jun 10.
• [3] Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance.Arthritis Res Ther. 2010;12(3):R116. doi: 10.1186/ar3053. Epub 2010 Jun 16.
• [4] Multiple sclerosis association study with the TENR-IL2-IL21 region in a Spanish population.Tissue Antigens. 2009 Sep;74(3):244-7. doi: 10.1111/j.1399-0039.2009.01298.x. Epub 2009 Jun 11.
• [5] Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.Nat Genet. 2011 Mar;43(3):246-52. doi: 10.1038/ng.764. Epub 2011 Feb 6.
• [6] 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.
• [7] 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.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.