Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP7IOJO)

• DOT Name: X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2)
• Synonyms: IL-1 receptor accessory protein-like 2; IL-1-RAPL-2; IL-1RAPL-2; IL1RAPL-2; EC 3.2.2.6; IL1RAPL-2-related protein; Interleukin-1 receptor 9; IL-1R-9; IL-1R9; Three immunoglobulin domain-containing IL-1 receptor-related 1; TIGIRR-1
• Gene Name: IL1RAPL2
• Related Disease:
  Schinzel-Giedion syndrome
  Autism
  Autism spectrum disorder
  Dermatomyositis
  Hepatitis C virus infection
  Myositis disease
  Polymyositis
  X-linked intellectual disability
• UniProt ID: IRPL2_HUMAN
• PDB ID: 7FD3; 7SZL
• EC Number: 3.2.2.6
• Pfam ID: PF07679 ; PF13895 ; PF01582
• Sequence:
  MKPPFLLALVVCSVVSTNLKMVSKRNSVDGCIDWSVDLKTYMALAGEPVRVKCALFYSYI
  RTNYSTAQSTGLRLMWYKNKGDLEEPIIFSEVRMSKEEDSIWFHSAEAQDSGFYTCVLRN
  STYCMKVSMSLTVAENESGLCYNSRIRYLEKSEVTKRKEISCPDMDDFKKSDQEPDVVWY
  KECKPKMWRSIIIQKGNALLIQEVQEEDGGNYTCELKYEGKLVRRTTELKVTALLTDKPP
  KPLFPMENQPSVIDVQLGKPLNIPCKAFFGFSGESGPMIYWMKGEKFIEELAGHIREGEI
  RLLKEHLGEKEVELALIFDSVVEADLANYTCHVENRNGRKHASVLLRKKDLIYKIELAGG
  LGAIFLLLVLLVVIYKCYNIELMLFYRQHFGADETNDDNKEYDAYLSYTKVDQDTLDCDN
  PEEEQFALEVLPDVLEKHYGYKLFIPERDLIPSGTYMEDLTRYVEQSRRLIIVLTPDYIL
  RRGWSIFELESRLHNMLVSGEIKVILIECTELKGKVNCQEVESLKRSIKLLSLIKWKGSK
  SSKLNSKFWKHLVYEMPIKKKEMLPRCHVLDSAEQGLFGELQPIPSIAMTSTSATLVSSQ
  ADLPEFHPSDSMQIRHCCRGYKHEIPATTLPVPSLGNHHTYCNLPLTLLNGQLPLNNTLK
  DTQEFHRNSSLLPLSSKELSFTSDIW
• Tissue Specificity: Detected at low levels in fetal and adult brain, in particular in the frontal lobe, temporal lobe and cerebellum. Detected at very low levels in skin, liver, fetal ovary and in placenta.
• Reactome Pathway: Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schinzel-Giedion syndrome	DISSBXAV	Definitive	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[4]
Myositis disease	DISCIXF0	Strong	Altered Expression	[3]
Polymyositis	DIS5DHFP	Strong	Altered Expression	[3]
X-linked intellectual disability	DISYJBY3	Strong	Genetic Variation	[2]

2 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 X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2).	[6]

References

• [1] Construction of a high-density and high-resolution human chromosome X array for comparative genomic hybridization analysis.J Hum Genet. 2007;52(5):397-405. doi: 10.1007/s10038-007-0127-4. Epub 2007 Apr 4.
• [2] Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD).Autism Res. 2011 Jun;4(3):228-33. doi: 10.1002/aur.187. Epub 2011 Feb 22.
• [3] Immunolocalization of interleukin-1 receptors in the sarcolemma and nuclei of skeletal muscle in patients with idiopathic inflammatory myopathies.Arthritis Rheum. 2007 Feb;56(2):674-87. doi: 10.1002/art.22388.
• [4] Analysis of interleukin (IL)-1beta IL-1 receptor antagonist, soluble IL-1 receptor type II and IL-1 accessory protein in HCV-associated lymphoproliferative disorders.Oncol Rep. 2006 May;15(5):1305-8.
• [5] 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.
• [6] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [7] 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.