Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYL8SDO)

• DOT Name: Complement factor H-related protein 3 (CFHR3)
• Synonyms: FHR-3; DOWN16; H factor-like protein 3
• Gene Name: CFHR3
• Related Disease:
  Atypical hemolytic uremic syndrome
  Hemolytic-uremic syndrome
  IgA nephropathy
  Non-immunoglobulin-mediated membranoproliferative glomerulonephritis
  Thrombotic microangiopathy
  Age-related macular degeneration
  Graft-versus-host disease
  Meningococcal disease
  Prostate cancer
  Prostate carcinoma
  Follicular lymphoma
  Thrombotic thrombocytopenic purpura
  B-cell neoplasm
  Chronic renal failure
  End-stage renal disease
  Hemolytic uremic syndrome, atypical, susceptibility to, 1
  Hepatocellular carcinoma
  Lupus nephritis
  Nephropathy
• UniProt ID: FHR3_HUMAN
• Pfam ID: PF00084
• Sequence:
  MLLLINVILTLWVSCANGQVKPCDFPDIKHGGLFHENMRRPYFPVAVGKYYSYYCDEHFE
  TPSGSYWDYIHCTQNGWSPAVPCLRKCYFPYLENGYNQNYGRKFVQGNSTEVACHPGYGL
  PKAQTTVTCTEKGWSPTPRCIRVRTCSKSDIEIENGFISESSSIYILNKEIQYKCKPGYA
  TADGNSSGSITCLQNGWSAQPICINSSEKCGPPPPISNGDTTSFLLKVYVPQSRVEYQCQ
  PYYELQGSNYVTCSNGEWSEPPRCIHPCIITEENMNKNNIKLKGRSDRKYYAKTGDTIEF
  MCKLGYNANTSILSFQAVCREGIVEYPRCE
• Function: Might be involved in complement regulation.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway: Regulation of Complement cascade (R-HSA-977606)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atypical hemolytic uremic syndrome	DIS6FUDJ	Strong	Biomarker	[1]
Hemolytic-uremic syndrome	DISSCBGW	Strong	Genetic Variation	[2]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[3]
Non-immunoglobulin-mediated membranoproliferative glomerulonephritis	DISLMV1J	Strong	Genetic Variation	[4]
Thrombotic microangiopathy	DISLZ0VW	Strong	Genetic Variation	[5]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[1]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[6]
Meningococcal disease	DISGDM2Z	moderate	Genetic Variation	[7]
Prostate cancer	DISF190Y	moderate	Biomarker	[6]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[6]
Follicular lymphoma	DISVEUR6	Disputed	Biomarker	[8]
Thrombotic thrombocytopenic purpura	DIS3LDOU	Disputed	Biomarker	[9]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[1]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[10]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[10]
Hemolytic uremic syndrome, atypical, susceptibility to, 1	DIS5NG8S	Limited	Unknown	[4]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[11]
Lupus nephritis	DISCVGPZ	Limited	Biomarker	[12]
Nephropathy	DISXWP4P	Limited	Biomarker	[1]

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 Complement factor H-related protein 3 (CFHR3).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Complement factor H-related protein 3 (CFHR3).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Complement factor H-related protein 3 (CFHR3).	[15]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Complement factor H-related protein 3 (CFHR3).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Complement factor H-related protein 3 (CFHR3).	[17]

References

• [1] Complement factor Hrelated 3 overexpression affects hepatocellular carcinoma proliferation and apoptosis.Mol Med Rep. 2019 Sep;20(3):2694-2702. doi: 10.3892/mmr.2019.10514. Epub 2019 Jul 23.
• [2] Atypical presentation of atypical haemolytic uraemic syndrome.BMJ Case Rep. 2018 Feb 11;2018:bcr2017222560. doi: 10.1136/bcr-2017-222560.
• [3] Variation in complement factor H affects complement activation in immunoglobulin A vasculitis with nephritis.Nephrology (Carlton). 2020 Jan;25(1):40-47. doi: 10.1111/nep.13580. Epub 2019 May 5.
• [4] A hybrid CFHR3-1 gene causes familial C3 glomerulopathy. J Am Soc Nephrol. 2012 Jul;23(7):1155-60. doi: 10.1681/ASN.2012020166. Epub 2012 May 24.
• [5] A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant-associated Thrombotic Microangiopathy Who was Treated With Eculizumab.J Pediatr Hematol Oncol. 2018 Nov;40(8):e544-e546. doi: 10.1097/MPH.0000000000000986.
• [6] Copy number polymorphisms in new HapMap III and Singapore populations.J Hum Genet. 2011 Aug;56(8):552-60. doi: 10.1038/jhg.2011.54. Epub 2011 Jun 16.
• [7] Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome.Mol Immunol. 2015 Oct;67(2 Pt B):276-86. doi: 10.1016/j.molimm.2015.06.021. Epub 2015 Jul 7.
• [8] Complement-Regulatory Proteins CFHR1 and CFHR3 and Patient Response to Anti-CD20 Monoclonal Antibody Therapy.Clin Cancer Res. 2017 Feb 15;23(4):954-961. doi: 10.1158/1078-0432.CCR-16-1275. Epub 2016 Aug 15.
• [9] Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles.Mol Immunol. 2009 Sep;46(14):2801-7. doi: 10.1016/j.molimm.2009.05.018. Epub 2009 Jul 28.
• [10] The autoimmune disease DEAP-hemolytic uremic syndrome.Semin Thromb Hemost. 2010 Sep;36(6):625-32. doi: 10.1055/s-0030-1262884. Epub 2010 Sep 23.
• [11] CFHR3 is a potential novel biomarker for hepatocellular carcinoma.J Cell Biochem. 2020 Apr;121(4):2970-2980. doi: 10.1002/jcb.29551. Epub 2019 Nov 10.
• [12] The clinical significance of plasma CFHR 1-5 in lupus nephropathy.Immunobiology. 2019 May;224(3):339-346. doi: 10.1016/j.imbio.2019.03.005. Epub 2019 Apr 3.
• [13] 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.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [17] 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.