Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHD4Y9D)

• DOT Name: Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4)
• Synonyms: C1q/TNF-related protein 4
• Gene Name: C1QTNF4
• Related Disease:
  Bacterial meningitis
  Cardiovascular disease
  Herpes simplex encephalitis
  Meningeal tuberculosis
  Osteoporosis
  Neoplasm
• UniProt ID: C1QT4_HUMAN
• Pfam ID: PF00386
• Sequence:
  MLPLLLGLLGPAACWALGPTPGPGSSELRSAFSAARTTPLEGTSEMAVTFDKVYVNIGGD
  FDVATGQFRCRVPGAYFFSFTAGKAPHKSLSVMLVRNRDEVQALAFDEQRRPGARRAASQ
  SAMLQLDYGDTVWLRLHGAPQYALGAPGATFSGYLVYADADADAPARGPPAPPEPRSAFS
  AARTRSLVGSDAGPGPRHQPLAFDTEFVNIGGDFDAAAGVFRCRLPGAYFFSFTLGKLPR
  KTLSVKLMKNRDEVQAMIYDDGASRRREMQSQSVMLALRRGDAVWLLSHDHDGYGAYSNH
  GKYITFSGFLVYPDLAPAAPPGLGASELL
• Function: May be involved in the regulation of the inflammatory network. Its role as pro- or anti-inflammatory seems to be context dependent. Seems to have some role in regulating food intake and energy balance when administered in the brain. This effect is sustained over a two-day period, and it is accompanied by decreased expression of orexigenic neuropeptides in the hypothalamus 3 hours post-injection.
• Tissue Specificity: Widely expressed at low levels . Highest levels in adipocyte tissue and brain .

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacterial meningitis	DISRP9SL	Strong	Altered Expression	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Herpes simplex encephalitis	DISGX28I	Strong	Altered Expression	[1]
Meningeal tuberculosis	DIS8KHDE	Strong	Altered Expression	[1]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]

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 tumor necrosis factor-related protein 4 (C1QTNF4).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Complement C1q tumor necrosis factor-related protein 4 (C1QTNF4).	[9]

References

• [1] C1Q/TNF-related protein 4 expression correlates with herpes simplex encephalitis progression.Ann Transl Med. 2019 Jun;7(11):235. doi: 10.21037/atm.2019.05.01.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] Ctrp4, a new adipokine, promotes the differentiation of osteoblasts.Biochem Biophys Res Commun. 2019 Apr 30;512(2):224-229. doi: 10.1016/j.bbrc.2019.03.053. Epub 2019 Mar 15.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.