Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUOO2XS)

• DOT Name: Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA)
• Synonyms: GM-CSF-R-alpha; GMCSFR-alpha; GMR-alpha; CDw116; CD antigen CD116
• Gene Name: CSF2RA
• Related Disease:
  Surfactant metabolism dysfunction, pulmonary, 4
  Hereditary pulmonary alveolar proteinosis
• UniProt ID: CSF2R_HUMAN
• PDB ID: 4NKQ; 4RS1
• Pfam ID: PF18611 ; PF09240
• Sequence:
  MLLLVTSLLLCELPHPAFLLIPEKSDLRTVAPASSLNVRFDSRTMNLSWDCQENTTFSKC
  FLTDKKNRVVEPRLSNNECSCTFREICLHEGVTFEVHVNTSQRGFQQKLLYPNSGREGTA
  AQNFSCFIYNADLMNCTWARGPTAPRDVQYFLYIRNSKRRREIRCPYYIQDSGTHVGCHL
  DNLSGLTSRNYFLVNGTSREIGIQFFDSLLDTKKIERFNPPSNVTVRCNTTHCLVRWKQP
  RTYQKLSYLDFQYQLDVHRKNTQPGTENLLINVSGDLENRYNFPSSEPRAKHSVKIRAAD
  VRILNWSSWSEAIEFGSDDGNLGSVYIYVLLIVGTLVCGIVLGFLFKRFLRIQRLFPPVP
  QIKDKLNDNHEVEDEIIWEEFTPEEGKGYREEVLTVKEIT
• Function: Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  Surfactant metabolism (R-HSA-5683826)
  Defective CSF2RB causes SMDP5 (R-HSA-5688849)
  Defective CSF2RA causes SMDP4 (R-HSA-5688890)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Surfactant metabolism dysfunction, pulmonary, 4	DISYD0O0	Strong	Autosomal recessive	[1]
Hereditary pulmonary alveolar proteinosis	DISQC53I	Supportive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA) affects the response to substance of Topotecan.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Granulocyte-macrophage colony-stimulating factor receptor subunit alpha (CSF2RA).	[8]

References

• [1] Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med. 2008 Nov 24;205(12):2703-10. doi: 10.1084/jem.20080990. Epub 2008 Oct 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [6] 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.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.