Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3PWOH6)

• DOT Name: Butyrophilin-like protein 9 (BTNL9)
• Gene Name: BTNL9
• Related Disease:
  Advanced cancer
  Dilated cardiomyopathy 1A
  Matthew-Wood syndrome
  Mycobacterium infection
  Neoplasm
  Uveal Melanoma
• UniProt ID: BTNL9_HUMAN
• Pfam ID: PF13765 ; PF00622 ; PF07686
• Sequence:
  MVDLSVSPDSLKPVSLTSSLVFLMHLLLLQPGEPSSEVKVLGPEYPILALVGEEVEFPCH
  LWPQLDAQQMEIRWFRSQTFNVVHLYQEQQELPGRQMPAFRNRTKLVKDDIAYGSVVLQL
  HSIIPSDKGTYGCRFHSDNFSGEALWELEVAGLGSDPHLSLEGFKEGGIQLRLRSSGWYP
  KPKVQWRDHQGQCLPPEFEAIVWDAQDLFSLETSVVVRAGALSNVSVSIQNLLLSQKKEL
  VVQIADVFVPGASAWKSAFVATLPLLLVLAALALGVLRKQRRSREKLRKQAEKRQEKLTA
  ELEKLQTELDWRRAEGQAEWRAAQKYAVDVTLDPASAHPSLEVSEDGKSVSSRGAPPGPA
  PGHPQRFSEQTCALSLERFSAGRHYWEVHVGRRSRWFLGACLAAVPRAGPARLSPAAGYW
  VLGLWNGCEYFVLAPHRVALTLRVPPRRLGVFLDYEAGELSFFNVSDGSHIFTFHDTFSG
  ALCAYFRPRAHDGGEHPDPLTICPLPVRGTGVPEENDSDTWLQPYEPADPALDWW
• Reactome Pathway: Butyrophilin (BTN) family interactions (R-HSA-8851680)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[2]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[3]
Mycobacterium infection	DISNSMUD	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[1]

3 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 Butyrophilin-like protein 9 (BTNL9).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Butyrophilin-like protein 9 (BTNL9).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Butyrophilin-like protein 9 (BTNL9).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Butyrophilin-like protein 9 (BTNL9).	[8]

References

• [1] Butyrophilin-Like 9 (BTNL9) Suppresses Invasion and Correlates with Favorable Prognosis of Uveal Melanoma.Med Sci Monit. 2019 Apr 30;25:3190-3198. doi: 10.12659/MSM.914074.
• [2] Detection of differentially methylated gene promoters in failing and nonfailing human left ventricle myocardium using computation analysis.Physiol Genomics. 2013 Jul 15;45(14):597-605. doi: 10.1152/physiolgenomics.00013.2013. Epub 2013 May 21.
• [3] BTN3A is a prognosis marker and a promising target for V9V2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC).Oncoimmunology. 2017 Sep 21;7(1):e1372080. doi: 10.1080/2162402X.2017.1372080. eCollection 2017.
• [4] The Armadillo (Dasypus novemcinctus): A Witness but Not a Functional Example for the Emergence of the Butyrophilin 3/V9V2 System in Placental Mammals.Front Immunol. 2018 Feb 23;9:265. doi: 10.3389/fimmu.2018.00265. eCollection 2018.
• [5] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.