Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRQT8CK)

• DOT Name: Butyrophilin-like protein 8 (BTNL8)
• Gene Name: BTNL8
• Related Disease:
  Coeliac disease
  Knee osteoarthritis
  Major depressive disorder
• UniProt ID: BTNL8_HUMAN
• Pfam ID: PF13765 ; PF00622 ; PF07686
• Sequence:
  MALMLSLVLSLLKLGSGQWQVFGPDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFRGQF
  SSVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLRLENITVLDAGLYGCRISSQS
  YYQKAIWELQVSALGSVPLISITGYVDRDIQLLCQSSGWFPRPTAKWKGPQGQDLSTDSR
  TNRDMHGLFDVEISLTVQENAGSISCSMRHAHLSREVESRVQIGDTFFEPISWHLATKVL
  GILCCGLFFGIVGLKIFFSKFQWKIQAELDWRRKHGQAELRDARKHAVEVTLDPETAHPK
  LCVSDLKTVTHRKAPQEVPHSEKRFTRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRD
  DVDRRKEYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISF
  FNINDQSLIYTLTCRFEGLLRPYIEYPSYNEQNGTPIVICPVTQESEKEASWQRASAIPE
  TSNSESSSQATTPFLPRGEM
• Function: May stimulate primary immune response. Acts on T-cell stimulated sub-optimally through the TCR/CD3 complex stimulating their proliferation and cytokine production.
• Tissue Specificity: Expressed in neutrophils. Isoforms 1 and 5 are expressed at high levels in the colon, lung,testis, lymph nodes and thyroid tissue. Isoform 5, but not isoform 1, is detected in spleen.
• Reactome Pathway: Butyrophilin (BTN) family interactions (R-HSA-8851680)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coeliac disease	DISIY60C	Strong	Biomarker	[1]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[2]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Butyrophilin-like protein 8 (BTNL8).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Butyrophilin-like protein 8 (BTNL8).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Butyrophilin-like protein 8 (BTNL8).	[9]

References

• [1] Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease.Cell. 2019 Feb 21;176(5):967-981.e19. doi: 10.1016/j.cell.2018.12.039. Epub 2019 Feb 7.
• [2] Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nat Genet. 2018 Apr;50(4):549-558. doi: 10.1038/s41588-018-0079-y. Epub 2018 Mar 20.
• [3] Differentially expressed genes related to major depressive disorder and antidepressant response: genome-wide gene expression analysis.Exp Mol Med. 2018 Aug 3;50(8):1-11. doi: 10.1038/s12276-018-0123-0.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.