Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLE5U1P)

• DOT Name: Complement C1q subcomponent subunit C (C1QC)
• Gene Name: C1QC
• Related Disease:
  Amyloidosis
  C1Q deficiency
  Complement deficiency
  Late-onset Parkinson disease
  leukaemia
  Lupus
  Marginal zone lymphoma
  Adenovirus infection
  Rett syndrome
• UniProt ID: C1QC_HUMAN
• PDB ID: 1PK6; 2JG8; 2JG9; 2WNU; 2WNV; 5HKJ; 5HZF; 6FCZ; 6Z6V
• Pfam ID: PF00386 ; PF01391
• Sequence:
  MDVGPSSLPHLGLKLLLLLLLLPLRGQANTGCYGIPGMPGLPGAPGKDGYDGLPGPKGEP
  GIPAIPGIRGPKGQKGEPGLPGHPGKNGPMGPPGMPGVPGPMGIPGEPGEEGRYKQKFQS
  VFTVTRQTHQPPAPNSLIRFNAVLTNPQGDYDTSTGKFTCKVPGLYYFVYHASHTANLCV
  LLYRSGVKVVTFCGHTSKTNQVNSGGVLLRLQVGEEVWLAVNDYYDMVGIQGSDSVFSGF
  LLFPD
• 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis	DISHTAI2	Strong	Biomarker	[1]
C1Q deficiency	DISWV4KU	Strong	Autosomal recessive	[2]
Complement deficiency	DISGN469	Strong	Biomarker	[3]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[4]
leukaemia	DISS7D1V	Strong	Genetic Variation	[5]
Lupus	DISOKJWA	Strong	Biomarker	[6]
Marginal zone lymphoma	DISLZ4AO	Strong	Genetic Variation	[7]
Adenovirus infection	DISUYSBZ	moderate	Biomarker	[8]
Rett syndrome	DISGG5UV	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Complement C1q subcomponent subunit C (C1QC).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Complement C1q subcomponent subunit C (C1QC).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Complement C1q subcomponent subunit C (C1QC).	[11]

References

• [1] Integrative approach to sporadic Alzheimer's disease:deficiency of TYROBPin cerebral A amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing A burden.Mol Psychiatry. 2019 Mar;24(3):431-446. doi: 10.1038/s41380-018-0255-6. Epub 2018 Oct 3.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families.Arthritis Rheum. 1996 Apr;39(4):663-70. doi: 10.1002/art.1780390419.
• [4] Variation in complement protein C1q is not a major contributor to cognitive impairment in Parkinson's disease.Neurosci Lett. 2015 May 6;594:66-9. doi: 10.1016/j.neulet.2015.03.048. Epub 2015 Mar 26.
• [5] Polymorphisms in innate immunity genes and risk of childhood leukemia.Hum Immunol. 2010 Jul;71(7):727-30. doi: 10.1016/j.humimm.2010.04.004. Epub 2010 May 16.
• [6] Evaluation of C1q genomic region in minority racial groups of lupus.Genes Immun. 2009 Jul;10(5):517-24. doi: 10.1038/gene.2009.33. Epub 2009 May 14.
• [7] Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma.Environ Mol Mutagen. 2012 Mar;53(2):145-51. doi: 10.1002/em.21675. Epub 2011 Dec 15.
• [8] Complement component C1q and anti-hexon antibody mediate adenovirus infection of a CAR-negative cell line.Viral Immunol. 2008 Dec;21(4):469-76. doi: 10.1089/vim.2008.0032.
• [9] Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.BMC Genomics. 2016 Jun 6;17:427. doi: 10.1186/s12864-016-2746-7.
• [10] 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.
• [11] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [12] 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.