Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2G1IOX)

• DOT Name: Complement C1q subcomponent subunit B (C1QB)
• Gene Name: C1QB
• Related Disease: C1Q deficiency
• UniProt ID: C1QB_HUMAN
• PDB ID: 1PK6; 2JG8; 2JG9; 2WNU; 2WNV; 5HKJ; 5HZF; 6FCZ; 6Z6V
• Pfam ID: PF00386 ; PF01391
• Sequence:
  MMMKIPWGSIPVLMLLLLLGLIDISQAQLSCTGPPAIPGIPGIPGTPGPDGQPGTPGIKG
  EKGLPGLAGDHGEFGEKGDPGIPGNPGKVGPKGPMGPKGGPGAPGAPGPKGESGDYKATQ
  KIAFSATRTINVPLRRDQTIRFDHVITNMNNNYEPRSGKFTCKVPGLYYFTYHASSRGNL
  CVNLMRGRERAQKVVTFCDYAYNTFQVTTGGMVLKLEQGENVFLQATDKNSLLGMEGANS
  IFSGFLLFPDMEA
• Function: C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
• KEGG Pathway:
  Efferocytosis (hsa04148)
  Complement and coagulation cascades (hsa04610)
  Alcoholic liver disease (hsa04936)
  Prion disease (hsa05020)
  Pertussis (hsa05133)
  Chagas disease (hsa05142)
  Staphylococcus aureus infection (hsa05150)
  Coro.virus disease - COVID-19 (hsa05171)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Classical antibody-mediated complement activation (R-HSA-173623)
  Regulation of Complement cascade (R-HSA-977606)
  Initial triggering of complement (R-HSA-166663)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
C1Q deficiency	DISWV4KU	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Complement C1q subcomponent subunit B (C1QB).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Complement C1q subcomponent subunit B (C1QB).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Complement C1q subcomponent subunit B (C1QB).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Complement C1q subcomponent subunit B (C1QB).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Complement C1q subcomponent subunit B (C1QB).	[6]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [3] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [4] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.