Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTATVST8)

• DOT Name: SLAM family member 8 (SLAMF8)
• Synonyms: B-lymphocyte activator macrophage expressed; BCM-like membrane protein; CD antigen CD353
• Gene Name: SLAMF8
• Related Disease:
  Advanced cancer
  Glioma
  Immune system disorder
  Inflammatory bowel disease
  Mastocytosis
  Hepatitis
  Crohn disease
• UniProt ID: SLAF8_HUMAN
• Sequence:
  MVMRPLWSLLLWEALLPITVTGAQVLSKVGGSVLLVAARPPGFQVREAIWRSLWPSEELL
  ATFFRGSLETLYHSRFLGRAQLHSNLSLELGPLESGDSGNFSVLMVDTRGQPWTQTLQLK
  VYDAVPRPVVQVFIAVERDAQPSKTCQVFLSCWAPNISEITYSWRRETTMDFGMEPHSLF
  TDGQVLSISLGPGDRDVAYSCIVSNPVSWDLATVTPWDSCHHEAAPGKASYKDVLLVVVP
  VSLLLMLVTLFSAWHWCPCSGKKKKDVHADRVGPETENPLVQDLP
• Function: May play a role in B-lineage commitment and/or modulation of signaling through the B-cell receptor.
• Tissue Specificity: Expressed in lymph node, spleen, thymus and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Immune system disorder	DISAEGPH	Strong	Biomarker	[1]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[2]
Mastocytosis	DIS1TEE0	Strong	Altered Expression	[3]
Hepatitis	DISXXX35	Disputed	Biomarker	[4]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SLAM family member 8 (SLAMF8).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SLAM family member 8 (SLAMF8).	[6]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of SLAM family member 8 (SLAMF8).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SLAM family member 8 (SLAMF8).	[8]

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 decreases the methylation of SLAM family member 8 (SLAMF8).	[9]

References

• [1] Costimulatory checkpoint SLAMF8 is an independent prognosis factor in glioma.CNS Neurosci Ther. 2019 Mar;25(3):333-342. doi: 10.1111/cns.13041. Epub 2018 Aug 13.
• [2] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [3] SLAM family member 8 is involved in oncogenic KIT-mediated signalling in human mastocytosis.Exp Dermatol. 2018 Jun;27(6):641-646. doi: 10.1111/exd.13523.
• [4] Combined deficiency of SLAMF8 and SLAMF9 prevents endotoxin-induced liver inflammation by downregulating TLR4 expression on macrophages.Cell Mol Immunol. 2020 Feb;17(2):153-162. doi: 10.1038/s41423-018-0191-z. Epub 2018 Dec 14.
• [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] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] 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.