Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0RLDOD)

• DOT Name: Fc receptor-like protein 2 (FCRL2)
• Synonyms: FcR-like protein 2; FcRL2; Fc receptor homolog 2; FcRH2; IFGP family protein 4; Immunoglobulin receptor translocation-associated protein 4; SH2 domain-containing phosphatase anchor protein 1; CD antigen CD307b
• Gene Name: FCRL2
• Related Disease:
  Autoimmune disease
  Small lymphocytic lymphoma
  Graves disease
  Hashimoto thyroiditis
  Hematologic disease
• UniProt ID: FCRL2_HUMAN
• Pfam ID: PF13895 ; PF13927
• Sequence:
  MLLWSLLVIFDAVTEQADSLTLVAPSSVFEGDSIVLKCQGEQNWKIQKMAYHKDNKELSV
  FKKFSDFLIQSAVLSDSGNYFCSTKGQLFLWDKTSNIVKIKVQELFQRPVLTASSFQPIE
  GGPVSLKCETRLSPQRLDVQLQFCFFRENQVLGSGWSSSPELQISAVWSEDTGSYWCKAE
  TVTHRIRKQSLQSQIHVQRIPISNVSLEIRAPGGQVTEGQKLILLCSVAGGTGNVTFSWY
  REATGTSMGKKTQRSLSAELEIPAVKESDAGKYYCRADNGHVPIQSKVVNIPVRIPVSRP
  VLTLRSPGAQAAVGDLLELHCEALRGSPPILYQFYHEDVTLGNSSAPSGGGASFNLSLTA
  EHSGNYSCEANNGLGAQCSEAVPVSISGPDGYRRDLMTAGVLWGLFGVLGFTGVALLLYA
  LFHKISGESSATNEPRGASRPNPQEFTYSSPTPDMEELQPVYVNVGSVDVDVVYSQVWSM
  QQPESSANIRTLLENKDSQVIYSSVKKS
• Function: May have an regulatory role in normal and neoplastic B cell development.
• Tissue Specificity: Expressed in the secondary lymphoid organs, spleen and lymph node. Expression is limited to the mature B-cell lines. Highly expressed in CD19 and within the mantle zones of the tonsil tissue. Isoform 2 is expressed in the spleen, peripheral blood and bone marrow. Isoform 2 and isoform 4 are expressed in B-cell lines. Preferentially expressed in memory B-cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[2]
Graves disease	DISU4KOQ	moderate	Biomarker	[3]
Hashimoto thyroiditis	DIS77CDF	moderate	Altered Expression	[3]
Hematologic disease	DIS9XD9A	moderate	Altered Expression	[2]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fc receptor-like protein 2 (FCRL2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fc receptor-like protein 2 (FCRL2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fc receptor-like protein 2 (FCRL2).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Fc receptor-like protein 2 (FCRL2).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fc receptor-like protein 2 (FCRL2).	[8]

References

• [1] Analysis of the Fc receptor-like-3 (FCRL3) locus in Caucasians with autoimmune disorders suggests a complex pattern of disease association.J Clin Endocrinol Metab. 2007 Mar;92(3):1106-11. doi: 10.1210/jc.2006-2183. Epub 2007 Jan 2.
• [2] FCRL2 mRNA expression is inversely associated with clinical progression in chronic lymphocytic leukemia.Eur J Haematol. 2009 Dec 1;83(6):541-9. doi: 10.1111/j.1600-0609.2009.01328.x. Epub 2009 Aug 4.
• [3] Expression Profile of Human Fc Receptor-Like 1, 2, and 4 Molecules in Peripheral Blood Mononuclear Cells of Patients with Hashimoto's Thyroiditis and Graves' Disease.Horm Metab Res. 2015 Aug;47(9):693-8. doi: 10.1055/s-0035-1545280. Epub 2015 Mar 4.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.