Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6MK4M1)

• DOT Name: Fc receptor-like A (FCRLA)
• Synonyms: Fc receptor homolog expressed in B-cells; Fc receptor-like and mucin-like protein 1; Fc receptor-like protein; Fc receptor-related protein X; FcRX
• Gene Name: FCRLA
• Related Disease:
  Advanced cancer
  B-cell lymphoma
  B-cell neoplasm
  Graves disease
  Melanoma
  Rheumatoid arthritis
  Autoimmune disease
  Hashimoto thyroiditis
  Lupus nephritis
  Neoplasm
  Small lymphocytic lymphoma
• UniProt ID: FCRLA_HUMAN
• PDB ID: 4HWN
• Pfam ID: PF13895
• Sequence:
  MKLGCVLMAWALYLSLGVLWVAQMLLAASFETLQCEGPVCTEESSCHTEDDLTDAREAGF
  QVKAYTFSEPFHLIVSYDWLILQGPAKPVFEGDLLVLRCQAWQDWPLTQVTFYRDGSALG
  PPGPNREFSITVVQKADSGHYHCSGIFQSPGPGIPETASVVAITVQELFPAPILRAVPSA
  EPQAGSPMTLSCQTKLPLQRSAARLLFSFYKDGRIVQSRGLSSEFQIPTASEDHSGSYWC
  EAATEDNQVWKQSPQLEIRVQGASSSAAPPTLNPAPQKSAAPGTAPEEAPGPLPPPPTPS
  SEDPGFSSPLGMPDPHLYHQMGLLLKHMQDVRVLLGHLLMELRELSGHRKPGTTKATAE
• Function: May be implicated in B-cell differentiation and lymphomagenesis.
• Tissue Specificity: Expressed specifically in primary and secondary lymphoid tissues like lymph node, spleen and tonsil. Specifically expressed in B-cells with a high level in normal germinal center B-cells, centroblasts and in a subset of diffuse large B-cell lymphomas. Highly expressed in bone marrow B-cells and weakly in earlier B lineage cells. Expressed in pre-germinal and germinal center B-cells in secondary lymphoid tissues. Also expressed in melanoma and melanocytes.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[1]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[1]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[5]
Hashimoto thyroiditis	DIS77CDF	moderate	Altered Expression	[5]
Lupus nephritis	DISCVGPZ	moderate	Genetic Variation	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Small lymphocytic lymphoma	DIS30POX	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fc receptor-like A (FCRLA).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Fc receptor-like A (FCRLA).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fc receptor-like A (FCRLA).	[10]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Fc receptor-like A (FCRLA).	[11]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Fc receptor-like A (FCRLA).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Fc receptor-like A (FCRLA).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Fc receptor-like A (FCRLA).	[15]

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 Fc receptor-like A (FCRLA).	[14]

References

• [1] An unusual Fc receptor-related protein expressed in human centroblasts.Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3776-81. doi: 10.1073/pnas.022042699. Epub 2002 Mar 12.
• [2] A refined study of FCRL genes from a genome-wide association study for Graves' disease.PLoS One. 2013;8(3):e57758. doi: 10.1371/journal.pone.0057758. Epub 2013 Mar 7.
• [3] Novel melanoma antigen, FCRL/FREB, identified by cDNA profile comparison using DNA chip are immunogenic in multiple melanoma patients.Int J Cancer. 2005 Mar 20;114(2):283-90. doi: 10.1002/ijc.20735.
• [4] Identification of pathogenic genes related to rheumatoid arthritis through integrated analysis of DNA methylation and gene expression profiling.Gene. 2017 Nov 15;634:62-67. doi: 10.1016/j.gene.2017.08.032. Epub 2017 Sep 4.
• [5] 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.
• [6] Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the FCGR2B-FCRLA Locus.J Rheumatol. 2016 Jun;43(6):1045-9. doi: 10.3899/jrheum.150665. Epub 2016 Mar 15.
• [7] 1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia.Clin Exp Med. 2019 May;19(2):261-267. doi: 10.1007/s10238-019-00551-0. Epub 2019 Mar 15.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [12] Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] 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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.