Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFO07H8)

• DOT Name: SPATS2-like protein (SPATS2L)
• Synonyms: DNA polymerase-transactivated protein 6; Stress granule and nucleolar protein; SGNP
• Gene Name: SPATS2L
• Related Disease:
  Adult respiratory distress syndrome
  Atrial fibrillation
  Early-onset anterior polar cataract
  Restless legs syndrome
  Familial atrial fibrillation
  Asthma
  Schizophrenia
• UniProt ID: SPS2L_HUMAN
• Pfam ID: PF07139
• Sequence:
  MAELNTHVNVKEKIYAVRSVVPNKSNNEIVLVLQQFDFNVDKAVQAFVDGSAIQVLKEWN
  MTGKKKNNKRKRSKSKQHQGNKDAKDKVERPEAGPLQPQPPQIQNGPMNGCEKDSSSTDS
  ANEKPALIPREKKISILEEPSKALRGVTEGNRLLQQKLSLDGNPKPIHGTTERSDGLQWS
  AEQPCNPSKPKAKTSPVKSNTPAAHLEIKPDELAKKRGPNIEKSVKDLQRCTVSLTRYRV
  MIKEEVDSSVKKIKAAFAELHNCIIDKEVSLMAEMDKVKEEAMEILTARQKKAEELKRLT
  DLASQMAEMQLAELRAEIKHFVSERKYDEELGKAARFSCDIEQLKAQIMLCGEITHPKNN
  YSSRTPCSSLLPLLNAHAATSGKQSNFSRKSSTHNKPSEGKAANPKMVSSLPSTADPSHQ
  TMPANKQNGSSNQRRRFNPQYHNNRLNGPAKSQGSGNEAEPLGKGNSRHEHRRQPHNGFR
  PKNKGGAKNQEASLGMKTPEAPAHSEKPRRRQHAADTSEARPFRGSVGRVSQCNLCPTRI
  EVSTDAAVLSVPAVTLVA

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[2]
Early-onset anterior polar cataract	DISTOPIY	Strong	Altered Expression	[3]
Restless legs syndrome	DISNWY00	Strong	Genetic Variation	[4]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]
Asthma	DISW9QNS	Limited	Biomarker	[5]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[6]

4 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 SPATS2-like protein (SPATS2L).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SPATS2-like protein (SPATS2L).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SPATS2-like protein (SPATS2L).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SPATS2-like protein (SPATS2L).	[22]

15 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 SPATS2-like protein (SPATS2L).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of SPATS2-like protein (SPATS2L).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SPATS2-like protein (SPATS2L).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SPATS2-like protein (SPATS2L).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SPATS2-like protein (SPATS2L).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SPATS2-like protein (SPATS2L).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of SPATS2-like protein (SPATS2L).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SPATS2-like protein (SPATS2L).	[15]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of SPATS2-like protein (SPATS2L).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SPATS2-like protein (SPATS2L).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SPATS2-like protein (SPATS2L).	[19]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of SPATS2-like protein (SPATS2L).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SPATS2-like protein (SPATS2L).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of SPATS2-like protein (SPATS2L).	[24]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of SPATS2-like protein (SPATS2L).	[25]

References

• [1] Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation.Respir Res. 2019 Jan 21;20(1):15. doi: 10.1186/s12931-019-0981-6.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] Sleep quality, BDNF genotype and gene expression in individuals with chronic abdominal pain.BMC Med Genomics. 2014 Oct 31;7:61. doi: 10.1186/s12920-014-0061-1.
• [4] Fine-mapping of restless legs locus 4 (RLS4) identifies a haplotype over the SPATS2L and KCTD18 genes.J Mol Neurosci. 2013 Mar;49(3):600-5. doi: 10.1007/s12031-012-9891-5. Epub 2012 Oct 2.
• [5] Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene.PLoS Genet. 2012 Jul;8(7):e1002824. doi: 10.1371/journal.pgen.1002824. Epub 2012 Jul 5.
• [6] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [7] 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.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] 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.
• [16] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [17] 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.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] 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.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [22] 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.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [25] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.