Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTACE5Y1)

• DOT Name: Complement factor H-related protein 2 (CFHR2)
• Synonyms: FHR-2; DDESK59; H factor-like 3; H factor-like protein 2
• Gene Name: CFHR2
• Related Disease:
  Type-1 diabetes
  Glycogen storage disease type II
  Non-immunoglobulin-mediated membranoproliferative glomerulonephritis
  Testicular cancer
  Non-insulin dependent diabetes
  Age-related macular degeneration
  Ankylosing spondylitis
• UniProt ID: FHR2_HUMAN
• PDB ID: 3ZD1; 5EA0
• Pfam ID: PF00084
• Sequence:
  MWLLVSVILISRISSVGGEAMFCDFPKINHGILYDEEKYKPFSQVPTGEVFYYSCEYNFV
  SPSKSFWTRITCAEEGWSPTPKCLRLCFFPFVENGHSESSGQTHLEGDTVQIICNTGYRL
  QNNENNISCVERGWSTPPKCRSTISAEKCGPPPPIDNGDITSFLLSVYAPGSSVEYQCQN
  LYQLEGNNQITCRNGQWSEPPKCLDPCVISQEIMEKYNIKLKWTNQQKLYSRTGDIVEFV
  CKSGYHPTKSHSFRAMCQNGKLVYPSCEEK
• Function: Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH. Can associate with lipoproteins and may play a role in lipid metabolism.
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[1]
Glycogen storage disease type II	DISXZPBC	Strong	Biomarker	[2]
Non-immunoglobulin-mediated membranoproliferative glomerulonephritis	DISLMV1J	Strong	Biomarker	[3]
Testicular cancer	DIS6HNYO	Strong	Genetic Variation	[4]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[5]
Age-related macular degeneration	DIS0XS2C	Limited	Genetic Variation	[6]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Complement factor H-related protein 2 (CFHR2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Complement factor H-related protein 2 (CFHR2).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Complement factor H-related protein 2 (CFHR2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Complement factor H-related protein 2 (CFHR2).	[11]

References

• [1] Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case-control study.Cardiovasc Diabetol. 2019 Mar 28;18(1):43. doi: 10.1186/s12933-019-0846-9.
• [2] The NEI/NCBI dbGAP database: genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration.BMC Med Genet. 2008 Jun 9;9:51. doi: 10.1186/1471-2350-9-51.
• [3] Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN.World J Nephrol. 2016 Jul 6;5(4):308-20. doi: 10.5527/wjn.v5.i4.308.
• [4] Age-specific familial risks in common cancers of the offspring.Int J Cancer. 1998 Oct 5;78(2):172-5. doi: 10.1002/(sici)1097-0215(19981005)78:2<172::aid-ijc9>3.0.co;2-w.
• [5] Identification of Novel Circulating Biomarkers Predicting Rapid Decline in Renal Function in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.Diabetes Care. 2017 Nov;40(11):1548-1555. doi: 10.2337/dc17-0911. Epub 2017 Aug 29.
• [6] Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.PLoS One. 2013;8(1):e53830. doi: 10.1371/journal.pone.0053830. Epub 2013 Jan 11.
• [7] CFHR2-rs2986127 as a genetic protective marker for acute anterior uveitis in Chinese patients.J Gene Med. 2016 Aug;18(8):193-8. doi: 10.1002/jgm.2890.
• [8] 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.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] 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.