Details of Drug Off-Target (DOT)

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

DOT Name	Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C)
Synonyms	IgG Fc receptor II-c; CDw32; Fc-gamma RII-c; Fc-gamma-RIIc; FcRII-c; CD antigen CD32
Gene Name	FCGR2C
Related Disease	Meningococcal disease ( ) Adult glioblastoma ( ) Anemia ( ) Bacterial infection ( ) Glioblastoma multiforme ( ) Graves disease ( ) Haemophilia A ( ) Hepatitis C virus infection ( ) HIV infectious disease ( ) leukaemia ( ) Leukemia ( ) Lupus ( ) Malaria ( ) Non-hodgkin lymphoma ( ) Plasma cell myeloma ( ) Rheumatoid arthritis ( ) Sarcoidosis ( ) Skin disease ( ) Systemic lupus erythematosus ( ) Transitional cell carcinoma ( ) Tuberculosis ( ) Meniere disease ( ) Plasmodium falciparum malaria ( ) Nephropathy ( ) Acute myelogenous leukaemia ( ) Colorectal carcinoma ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Lymphoma ( ) Neoplasm ( )
UniProt ID	FCG2C_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3WJL; 6YAX
Pfam ID	PF13895
Sequence	MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWIN VLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSL SDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAA VVALIYCRKKRISANSTDPVKAAQFEPPGRQMIAIRKRQPEETNNDYETADGGYMTLNPR APTDDDKNIYLTLPPNDHVNSNN
Function	Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells.
Tissue Specificity	Isoform IIC1 is detected in monocytes, macrophages, polymorphonuclear cells and natural killer cells.
KEGG Pathway	Phagosome (hsa04145 ) Osteoclast differentiation (hsa04380 ) Leishmaniasis (hsa05140 ) Staphylococcus aureus infection (hsa05150 ) Tuberculosis (hsa05152 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Meningococcal disease	DISGDM2Z	Definitive	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Genetic Variation	[3]
Bacterial infection	DIS5QJ9S	Strong	Genetic Variation	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Graves disease	DISU4KOQ	Strong	Altered Expression	[5]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[7]
HIV infectious disease	DISO97HC	Strong	Biomarker	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[9]
Leukemia	DISNAKFL	Strong	Biomarker	[9]
Lupus	DISOKJWA	Strong	Biomarker	[10]
Malaria	DISQ9Y50	Strong	Biomarker	[11]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[12]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[13]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[14]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[15]
Skin disease	DISDW8R6	Strong	Genetic Variation	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[18]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[19]
Meniere disease	DISC5R5F	moderate	Biomarker	[20]
Plasmodium falciparum malaria	DIS3Q9KF	moderate	Genetic Variation	[21]
Nephropathy	DISXWP4P	Disputed	Genetic Variation	[22]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[23]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[24]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[25]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[25]
Lymphoma	DISN6V4S	Limited	Biomarker	[26]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[27]
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⏷ Show the Full List of 30 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 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 Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[28]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[30]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[32]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Low affinity immunoglobulin gamma Fc region receptor II-c (FCGR2C).	[33]
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References

1	Meningococcal disease and polymorphism of FcgammaRIIa (CD32) in late complement component-deficient individuals.Clin Exp Immunol. 1998 Jan;111(1):97-101. doi: 10.1046/j.1365-2249.1998.00484.x.
2	Development of third generation anti-EGFRvIII chimeric T cells and EGFRvIII-expressing artificial antigen presenting cells for adoptive cell therapy for glioma.PLoS One. 2018 Jul 5;13(7):e0199414. doi: 10.1371/journal.pone.0199414. eCollection 2018.
3	Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children.Am J Trop Med Hyg. 2006 Apr;74(4):573-7.
4	Association of Fcgamma receptor IIa (CD32) polymorphism with severe malaria in West Africa.Am J Trop Med Hyg. 2003 Dec;69(6):565-8.
5	Decreased expression of FcRII in active Graves' disease patients.J Clin Lab Anal. 2019 Jul;33(6):e22904. doi: 10.1002/jcla.22904. Epub 2019 Apr 29.
6	CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall response by distinct mechanisms in vitro.Thromb Haemost. 2017 Aug 30;117(9):1679-1687. doi: 10.1160/TH17-03-0201. Epub 2017 May 11.
7	Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C.Sci Rep. 2019 Jun 19;9(1):8760. doi: 10.1038/s41598-019-45114-1.
8	CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.Sci Transl Med. 2018 Apr 18;10(437):eaar6759. doi: 10.1126/scitranslmed.aar6759.
9	Autoantigen inhibits apoptosis of a human B cell leukemia that produces pathogenic rheumatoid factor.J Immunol. 1993 Dec 15;151(12):7273-83.
10	Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice.Clin Exp Immunol. 2013 Nov;174(2):221-8. doi: 10.1111/cei.12164.
11	Pyruvate Kinase and Fc Receptor Gene Copy Numbers Associated With Malaria Phenotypes.J Infect Dis. 2017 Jul 15;216(2):276-282. doi: 10.1093/infdis/jix284.
12	Resistance to cytotoxic chemotherapy induced by CD40 ligand in lymphoma cells.Blood. 1998 Nov 1;92(9):3381-7.
13	C-reactive protein promotes bone destruction in human myeloma through the CD32-p38 MAPK-Twist axis.Sci Signal. 2017 Dec 12;10(509):eaan6282. doi: 10.1126/scisignal.aan6282.
14	Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still's Disease.Int J Mol Sci. 2017 Jan 19;18(1):202. doi: 10.3390/ijms18010202.
15	Polymorphism of FCGR2A, FCGR2C, and FCGR3B Genes in the Pathogenesis of Sarcoidosis.Adv Exp Med Biol. 2016;905:57-68. doi: 10.1007/5584_2015_193.
16	Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease: implications for the development of severe reactive onchodermatitis (ROD).Am J Trop Med Hyg. 2007 Dec;77(6):1074-8.
17	Genomic pathology of SLE-associated copy-number variation at the FCGR2C/FCGR3B/FCGR2B locus.Am J Hum Genet. 2013 Jan 10;92(1):28-40. doi: 10.1016/j.ajhg.2012.11.013. Epub 2012 Dec 20.
18	The effects of malignant transformation on susceptibility of human urothelial cells to CD40-mediated apoptosis.J Natl Cancer Inst. 2002 Sep 18;94(18):1381-95. doi: 10.1093/jnci/94.18.1381.
19	Neutrophil CD64, TLR2 and TLR4 expression increases but phagocytic potential decreases during tuberculosis.Tuberculosis (Edinb). 2018 Jul;111:135-142. doi: 10.1016/j.tube.2018.06.010. Epub 2018 Jun 9.
20	Polymorphisms of CD16A and CD32 Fc receptors and circulating immune complexes in Mnire's disease: a case-control study.BMC Med Genet. 2011 Jan 5;12:2. doi: 10.1186/1471-2350-12-2.
21	FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan.Malar J. 2009 Mar 13;8:43. doi: 10.1186/1475-2875-8-43.
22	Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients.Arthritis Rheum. 1995 Dec;38(12):1832-6. doi: 10.1002/art.1780381217.
23	Ribosomal proteins sustain morphology, function and phenotype in acute myeloid leukemia blasts.Leuk Res. 1998 Apr;22(4):329-39. doi: 10.1016/s0145-2126(97)00178-1.
24	In vitro elimination of epidermal growth factor receptor-overexpressing cancer cells by CD32A-chimeric receptor T cells in combination with cetuximab or panitumumab.Int J Cancer. 2020 Jan 1;146(1):236-247. doi: 10.1002/ijc.32663. Epub 2019 Oct 12.
25	C-reactive protein-derived peptide 201-206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32.J Leukoc Biol. 2011 Dec;90(6):1167-75. doi: 10.1189/jlb.0111032. Epub 2011 Sep 20.
26	Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue.Am J Surg Pathol. 1991 Sep;15(9):819-28. doi: 10.1097/00000478-199109000-00001.
27	Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.J Biol Chem. 2015 May 22;290(21):13017-27. doi: 10.1074/jbc.M115.650903. Epub 2015 Apr 7.
28	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.
29	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.
30	Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
31	The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
32	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.
33	Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.