Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGHZ7FU)

• DOT Name: Killer cell lectin-like receptor subfamily F member 1 (KLRF1)
• Synonyms: Lectin-like receptor F1; Activating coreceptor NKp80; C-type lectin domain family 5 member C
• Gene Name: KLRF1
• Related Disease:
  Haematological malignancy
  Neoplasm
  Tuberculosis
  leukaemia
  Leukemia
  Asthma
  Type-1 diabetes
• UniProt ID: KLRF1_HUMAN
• Pfam ID: PF00059
• Sequence:
  MQDEERYMTLNVQSKKRSSAQTSQLTFKDYSVTLHWYKILLGISGTVNGILTLTLISLIL
  LVSQGVLLKCQKGSCSNATQYEDTGDLKVNNGTRRNISNKDLCASRSADQTVLCQSEWLK
  YQGKCYWFSNEMKSWSDSYVYCLERKSHLLIIHDQLEMAFIQKNLRQLNYVWIGLNFTSL
  KMTWTWVDGSPIDSKIFFIKGPAKENSCAAIKESKIFSETCSSVFKWICQY
• Function: Involved in the natural killer (NK)-mediated cytolysis of PHA-induced lymphoblasts.
• Tissue Specificity: Strongly expressed in peripheral blood leukocytes and spleen, with weaker expression in lymph node and adult liver, and no expression detected in bone marrow, thymus, and fetal liver. Not expressed in brain, heart, placenta, lung, kidney, skeletal muscle, and pancreas. Within peripheral blood leukocyte and immunocyte cell lines, expression was predominant in NK cells but was also detected in monocytes.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Haematological malignancy	DISCDP7W	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[3]
leukaemia	DISS7D1V	moderate	Biomarker	[4]
Leukemia	DISNAKFL	moderate	Biomarker	[4]
Asthma	DISW9QNS	Limited	Altered Expression	[5]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Killer cell lectin-like receptor subfamily F member 1 (KLRF1).	[6]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Killer cell lectin-like receptor subfamily F member 1 (KLRF1).	[7]
Choline	DM5D9YK	Investigative	Choline affects the expression of Killer cell lectin-like receptor subfamily F member 1 (KLRF1).	[9]

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 affects the methylation of Killer cell lectin-like receptor subfamily F member 1 (KLRF1).	[8]

References

• [1] Tumor cells of non-hematopoietic and hematopoietic origins express activation-induced C-type lectin, the ligand for killer cell lectin-like receptor F1.Int Immunol. 2010 Sep;22(9):783-90. doi: 10.1093/intimm/dxq430. Epub 2010 Jul 26.
• [2] NKT-Like (CD3+CD56+) Cells in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors.Front Immunol. 2019 Oct 22;10:2493. doi: 10.3389/fimmu.2019.02493. eCollection 2019.
• [3] Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil-ANRS 12274.Front Immunol. 2019 Aug 13;10:1800. doi: 10.3389/fimmu.2019.01800. eCollection 2019.
• [4] Generation and preclinical characterization of an NKp80-Fc fusion protein for redirected cytolysis of natural killer (NK) cells against leukemia.J Biol Chem. 2015 Sep 11;290(37):22474-84. doi: 10.1074/jbc.M115.678912. Epub 2015 Jul 21.
• [5] Bioinformatics analysis of gene expression in peripheral blood mononuclear cells from children with type 1 diabetes in 3 periods.Exp Clin Endocrinol Diabetes. 2014 Sep;122(8):477-83. doi: 10.1055/s-0034-1372599. Epub 2014 May 16.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] In-vivo effects of simvastatin and rosuvastatin on global gene expression in peripheral blood leucocytes in a human inflammation model. Pharmacogenet Genomics. 2008 Feb;18(2):109-20.
• [8] 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.
• [9] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.