Details of Drug Off-Target (DOT)

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

• DOT Name: Complement factor H-related protein 4 (CFHR4)
• Synonyms: FHR-4
• Gene Name: CFHR4
• Related Disease:
  Atypical hemolytic uremic syndrome
  Glycogen storage disease type II
  Systemic lupus erythematosus
  Age-related macular degeneration
• UniProt ID: FHR4_HUMAN
• Pfam ID: PF00084
• Sequence:
  MLLLINVILTLWVSCANGQEVKPCDFPEIQHGGLYYKSLRRLYFPAAAGQSYSYYCDQNF
  VTPSGSYWDYIHCTQDGWSPTVPCLRTCSKSDVEIENGFISESSSIYILNEETQYNCKPG
  YATAEGNSSGSITCLQNGWSTQPICIKFCDMPVFENSRAKSNGMWFKLHDTLDYECYDGY
  ESSYGNTTDSIVCGEDGWSHLPTCYNSSENCGPPPPISNGDTTSFPQKVYLPWSRVEYQC
  QSYYELQGSKYVTCSNGDWSEPPRCISMKPCEFPEIQHGHLYYENTRRPYFPVATGQSYS
  YYCDQNFVTPSGSYWDYIHCTQDGWLPTVPCLRTCSKSDIEIENGFISESSSIYILNKEI
  QYKCKPGYATADGNSSGSITCLQNGWSAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLD
  YECYDGYEISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFLLKVYVPQ
  SRVEYQCQSYYELQGSNYVTCSNGEWSEPPRCIHPCIITEENMNKNNIQLKGKSDIKYYA
  KTGDTIEFMCKLGYNANTSVLSFQAVCREGIVEYPRCE
• Function: Involved in complement regulation. 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atypical hemolytic uremic syndrome	DIS6FUDJ	Strong	Biomarker	[1]
Glycogen storage disease type II	DISXZPBC	Strong	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[3]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Complement factor H-related protein 4 (CFHR4).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Complement factor H-related protein 4 (CFHR4).	[6]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Complement factor H-related protein 4 (CFHR4).	[7]

References

• [1] Hemolytic Uremic Syndrome in an Infant with Primary Hyperoxaluria Type II: An Unreported Clinical Association.Nephron. 2019;142(3):264-270. doi: 10.1159/000497823. Epub 2019 Mar 19.
• [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] Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility.PLoS Genet. 2011 May;7(5):e1002079. doi: 10.1371/journal.pgen.1002079. Epub 2011 May 26.
• [4] Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation: Implications in Age-Related Macular Degeneration.Ophthalmology. 2018 Jul;125(7):1064-1074. doi: 10.1016/j.ophtha.2017.12.023. Epub 2018 Feb 2.
• [5] 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.
• [6] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [7] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.