Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5Q24MV)

• DOT Name: Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5)
• Synonyms: CD85 antigen-like family member F; Immunoglobulin-like transcript 11; ILT-11; Leukocyte immunoglobulin-like receptor 9; LIR-9; CD antigen CD85f
• Gene Name: LILRA5
• Related Disease:
  Juvenile idiopathic arthritis
  Thalassemia
• UniProt ID: LIRA5_HUMAN
• PDB ID: 2D3V
• Pfam ID: PF13895
• Sequence:
  MAPWSHPSAQLQPVGGDAVSPALMVLLCLGLSLGPRTHVQAGNLSKATLWAEPGSVISRG
  NSVTIRCQGTLEAQEYRLVKEGSPEPWDTQNPLEPKNKARFSIPSMTEHHAGRYRCYYYS
  PAGWSEPSDPLELVVTGFYNKPTLSALPSPVVTSGENVTLQCGSRLRFDRFILTEEGDHK
  LSWTLDSQLTPSGQFQALFPVGPVTPSHRWMLRCYGSRRHILQVWSEPSDLLEIPVSGAA
  DNLSPSQNKSDSGTASHLQDYAVENLIRMGMAGLILVVLGILIFQDWHSQRSPQAAAGR
• Function: May play a role in triggering innate immune responses. Does not seem to play a role for any class I MHC antigen recognition.
• Tissue Specificity: Expressed mostly in tissues of the hematopoietic system, including bone marrow, spleen, lymph node and peripheral leukocytes. Among leukocytes, monocytes and neutrophils express the highest level. Expressed in CD14+ monocytes, but not in T-cells, B-cells or natural killer (NK) cells (at protein level).
• KEGG Pathway:
  Osteoclast differentiation (hsa04380)
  B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[1]
Thalassemia	DIS76XZB	Limited	Genetic Variation	[2]

4 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 Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5).	[6]

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 decreases the methylation of Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5).	[7]

References

• [1] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [2] First report on the co-inheritance of (beta) IVS I-1 (G-->T) Thalassemia with the (gamma) CD85 [Phe-->Ser (F1) (TTT-->TCT)] HbA2 Etolia in Iran.Haematologica. 2006 Jun;91(6 Suppl):ECR15.
• [3] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [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.