Details of Drug Off-Target (DOT)

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

• DOT Name: Fc receptor-like protein 6 (FCRL6)
• Synonyms: FcR-like protein 6; FcRL6; Fc receptor homolog 6; FcRH6; IFGP6
• Gene Name: FCRL6
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Autism
  Esophageal cancer
  Hematologic disease
  Neoplasm
  Systemic lupus erythematosus
  Systemic sclerosis
  Disseminated intravascular coagulation
• UniProt ID: FCRL6_HUMAN
• Pfam ID: PF13895 ; PF13927
• Sequence:
  MLLWTAVLLFVPCVGKTVWLYLQAWPNPVFEGDALTLRCQGWKNTPLSQVKFYRDGKFLH
  FSKENQTLSMGAATVQSRGQYSCSGQVMYIPQTFTQTSETAMVQVQELFPPPVLSAIPSP
  EPREGSLVTLRCQTKLHPLRSALRLLFSFHKDGHTLQDRGPHPELCIPGAKEGDSGLYWC
  EVAPEGGQVQKQSPQLEVRVQAPVSRPVLTLHHGPADPAVGDMVQLLCEAQRGSPPILYS
  FYLDEKIVGNHSAPCGGTTSLLFPVKSEQDAGNYSCEAENSVSRERSEPKKLSLKGSQVL
  FTPASNWLVPWLPASLLGLMVIAAALLVYVRSWRKAGPLPSQIPPTAPGGEQCPLYANVH
  HQKGKDEGVVYSVVHRTSKRSEARSAEFTVGRKDSSIICAEVRCLQPSEVSSTEVNMRSR
  TLQEPLSDCEEVLC
• Function: Acts as a MHC class II receptor. When stimulated on its own, does not play a role in cytokine production or the release of cytotoxic granules by NK cells and cytotoxic CD8(+) T cells. Does not act as an Fc receptor.
• Tissue Specificity: Expressed by cytolytic cells including NK cells, effector and effector-memory CD8(+) T-cells, and a subset of NKT cells (at protein level) . Also expressed in gamma delta T cells and in a rare subset of effector CD4(+) T-cells (at protein level) . Expressed in spleen, skin, peripheral blood leukocytes, liver, lung, bone marrow, small intestine and placenta . Expression among T-cells is greatly expanded in HIV-1 infected individuals, and includes not only effector and effector-memory CD8(+) T-cells but also populations of CD4(+) T-cells . Expression among CD8(+) T-cells and NK cells is expanded in individuals with chronic lymphocytic leukemia (CLL) but is reduced in PBMCs from patients with acute (AML), chronic myeloid leukemia (CML) and non-Hodgkin's lymphoma . Expression is higher in PBMCs and/or CD3(+) cells of patients with autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenia purpura (ITP) . In contrast, expression in CD3(+) cells from patients with lupus anticoagulans (LA) is higher .

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[3]
Hematologic disease	DIS9XD9A	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[6]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[7]
Disseminated intravascular coagulation	DISCAVOZ	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Fc receptor-like protein 6 (FCRL6).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fc receptor-like protein 6 (FCRL6).	[11]

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 Fc receptor-like protein 6 (FCRL6).	[10]

References

• [1] Atherogenic lipids induce adhesion of human coronary artery smooth muscle cells to macrophages by up-regulating chemokine CX3CL1 on smooth muscle cells in a TNFalpha-NFkappaB-dependent manner.J Biol Chem. 2007 Jun 29;282(26):19167-76. doi: 10.1074/jbc.M701642200. Epub 2007 Apr 23.
• [2] Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.Brain Behav Immun. 2012 Oct;26(7):1122-7. doi: 10.1016/j.bbi.2012.07.014. Epub 2012 Aug 3.
• [3] Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations.Nat Genet. 2011 Jun 5;43(7):679-84. doi: 10.1038/ng.849.
• [4] FCRL6 receptor: expression and associated proteins.Immunol Lett. 2011 Jan 30;134(2):174-82. doi: 10.1016/j.imlet.2010.09.023. Epub 2010 Oct 7.
• [5] Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement.JCI Insight. 2018 Dec 20;3(24):e120360. doi: 10.1172/jci.insight.120360.
• [6] Extensive polymorphisms of LILRB1 (ILT2, LIR1) and their association with HLA-DRB1 shared epitope negative rheumatoid arthritis.Hum Mol Genet. 2005 Aug 15;14(16):2469-80. doi: 10.1093/hmg/ddi247. Epub 2005 Jul 13.
• [7] Deregulated PSGL-1 Expression in B Cells and Dendritic Cells May Be Implicated in Human Systemic Sclerosis Development.J Invest Dermatol. 2018 Oct;138(10):2123-2132. doi: 10.1016/j.jid.2018.04.003. Epub 2018 Apr 22.
• [8] Differential expression of leukocyte receptors in disseminated intravascular coagulation: prognostic value of low protein C receptor expression.Thromb Res. 2014 Nov;134(5):1130-4. doi: 10.1016/j.thromres.2014.08.026. Epub 2014 Sep 6.
• [9] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [10] 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.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.