Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN6DBCJ)

• DOT Name: Interleukin-11 receptor subunit alpha (IL11RA)
• Synonyms: IL-11 receptor subunit alpha; IL-11R subunit alpha; IL-11R-alpha; IL-11RA
• Gene Name: IL11RA
• Related Disease: Craniosynostosis and dental anomalies
• UniProt ID: I11RA_HUMAN
• PDB ID: 6O4P; 8DPS; 8DPT; 8DPU
• Sequence:
  MSSSCSGLSRVLVAVATALVSASSPCPQAWGPPGVQYGQPGRSVKLCCPGVTAGDPVSWF
  RDGEPKLLQGPDSGLGHELVLAQADSTDEGTYICQTLDGALGGTVTLQLGYPPARPVVSC
  QAADYENFSCTWSPSQISGLPTRYLTSYRKKTVLGADSQRRSPSTGPWPCPQDPLGAARC
  VVHGAEFWSQYRINVTEVNPLGASTRLLDVSLQSILRPDPPQGLRVESVPGYPRRLRASW
  TYPASWPCQPHFLLKFRLQYRPAQHPAWSTVEPAGLEEVITDAVAGLPHAVRVSARDFLD
  AGTWSTWSPEAWGTPSTGTIPKEIPAWGQLHTQPEVEPQVDSPAPPRPSLQPHPRLLDHR
  DSVEQVAVLASLGILSFLGLVAGALALGLWLRLRRGGKDGSPKPGFLASVIPVDRRPGAP
  NL
• Function: Receptor for interleukin-11 (IL11). The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells (Probable). Essential for the normal development of craniofacial bones and teeth. Restricts suture fusion and tooth number; [Soluble interleukin-11 receptor subunit alpha]: Soluble form of IL11 receptor (sIL11RA) that acts as an agonist of IL11 activity. The IL11:sIL11RA complex binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL11RA in a process called IL11 trans-signaling ; [Isoform HCR2]: Soluble form of IL11 receptor (sIL11RA) that acts as an agonist of IL11 activity. The IL11:sIL11RA complex binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL11RA in a process called IL11 trans-signaling.
• Tissue Specificity: Expressed in a number of cell lines, including the myelogenous leukemia cell line K-562, the megakaryocytic leukemia cell line M-07e, the erythroleukemia cell line TF-1, and the osteosarcoma cell lines, MG-63 and SaOS-2 . Also expressed in normal and malignant prostate epithelial cell lines. Expression levels are increased in prostate carcinoma.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway: IL-6-type cytokine receptor ligand interactions (R-HSA-6788467)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis and dental anomalies	DISNSW0F	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Interleukin-11 receptor subunit alpha (IL11RA).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interleukin-11 receptor subunit alpha (IL11RA).	[10]

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] 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.
• [3] 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.
• [4] Validation of reference gene stability for APAP hepatotoxicity studies in different in vitro systems and identification of novel potential toxicity biomarkers. Toxicol In Vitro. 2010 Oct;24(7):1962-70. doi: 10.1016/j.tiv.2010.08.007. Epub 2010 Aug 21.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.