Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-7 receptor subunit alpha (IL7R)
• Synonyms: IL-7 receptor subunit alpha; IL-7R subunit alpha; IL-7R-alpha; IL-7RA; CDw127; CD antigen CD127
• Gene Name: IL7R
• Related Disease:
  Immunodeficiency 104
  Omenn syndrome
  T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency
• UniProt ID: IL7RA_HUMAN
• PDB ID: 3DI2; 3DI3; 3UP1; 5J11; 6P50; 6P67; 7OPB
• Pfam ID: PF00041 ; PF18447
• Sequence:
  MTILGTTFGMVFSLLQVVSGESGYAQNGDLEDAELDDYSFSCYSQLEVNGSQHSLTCAFE
  DPDVNITNLEFEICGALVEVKCLNFRKLQEIYFIETKKFLLIGKSNICVKVGEKSLTCKK
  IDLTTIVKPEAPFDLSVVYREGANDFVVTFNTSHLQKKYVKVLMHDVAYRQEKDENKWTH
  VNLSSTKLTLLQRKLQPAAMYEIKVRSIPDHYFKGFWSEWSPSYYFRTPEINNSSGEMDP
  ILLTISILSFFSVALLVILACVLWKKRIKPIVWPSLPDHKKTLEHLCKKPRKNLNVSFNP
  ESFLDCQIHRVDDIQARDEVEGFLQDTFPQQLEESEKQRLGGDVQSPNCPSEDVVITPES
  FGRDSSLTCLAGNVSACDAPILSSSRSLDCRESGKNGPHVYQDLLLSLGTTNSTLPPPFS
  LQSGILTLNPVAQGQPILTSLGSNQEEAYVTMSSFYQNQ
• Function: Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO sig.ling pathway (hsa04068)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Interleukin-7 signaling (R-HSA-1266695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 104	DISJFQSY	Definitive	Autosomal recessive	[1]
Omenn syndrome	DIS2C887	Supportive	Autosomal recessive	[2]
T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency	DISIXVJR	Supportive	Autosomal recessive	[2]

30 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-7 receptor subunit alpha (IL7R).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Interleukin-7 receptor subunit alpha (IL7R).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Interleukin-7 receptor subunit alpha (IL7R).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[14]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[17]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[18]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[19]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[20]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[6]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[21]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[20]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[23]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[26]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[20]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[27]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Interleukin-7 receptor subunit alpha (IL7R).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Interleukin-7 receptor subunit alpha (IL7R).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-7 receptor subunit alpha (IL7R).	[24]

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] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [3] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [7] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [8] 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.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Distinct genetic profile in peripheral blood mononuclear cells of psoriatic arthritis patients treated with methotrexate and TNF-inhibitors. Clin Rheumatol. 2014 Dec;33(12):1815-21. doi: 10.1007/s10067-014-2807-8. Epub 2014 Oct 24.
• [13] Down-regulation of IL-7Ralpha expression in human T cells via DNA methylation. J Immunol. 2007 May 1;178(9):5473-9. doi: 10.4049/jimmunol.178.9.5473.
• [14] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [15] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [16] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders. Cancer Genet Cytogenet. 2010 Jun;199(2):110-20. doi: 10.1016/j.cancergencyto.2010.02.010.
• [19] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [20] Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes. Toxicol Lett. 2010 Nov 10;199(1):51-9.
• [21] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [22] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [23] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [24] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [25] 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.
• [26] 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.
• [27] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.