Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8OO0M)

• DOT Name: Sine oculis-binding protein homolog (SOBP)
• Synonyms: Jackson circler protein 1
• Gene Name: SOBP
• Related Disease:
  Intellectual disability
  B-cell neoplasm
  Neoplasm
  Psychotic disorder
  Intellectual disability, anterior maxillary protrusion, and strabismus
  Syndromic intellectual disability
• UniProt ID: SOBP_HUMAN
• Pfam ID: PF15279
• Sequence:
  MAEMEKEGRPPENKRSRKPAHPVKREINEEMKNFAENTMNELLGWYGYDKVELKDGEDIE
  FRSYPTDGESRQHISVLKENSLPKPKLPEDSVISPYNISTGYSGLATGNGLSDSPAGSKD
  HGSVPIIVPLIPPPFIKPPAEDDVSNVQIMCAWCQKVGIKRYSLSMGSEVKSFCSEKCFA
  ACRRAYFKRNKARDEDGHAENFPQQHYAKETPRLAFKNNCELLVCDWCKHIRHTKEYLDF
  GDGERRLQFCSAKCLNQYKMDIFYKETQANLPAGLCSTLHPPMENKAEGTGVQLLTPDSW
  NIPLTDARRKAPSPVATAGQSQGPGPSASTTVSPSDTANCSVTKIPTPVPKSIPISETPN
  IPPVSVQPPASIGPPLGVPPRSPPMVMTNRGPVPLPIFMEQQIMQQIRPPFIRGPPHHAS
  NPNSPLSNPMLPGIGPPPGGPRNLGPTSSPMHRPMLSPHIHPPSTPTMPGNPPGLLPPPP
  PGAPLPSLPFPPVSMMPNGPMPVPQMMNFGLPSLAPLVPPPTLLVPYPVIVPLPVPIPIP
  IPIPHVSDSKPPNGFSSNGENFIPNAPGDSAAAGGKPSGHSLSPRDSKQGSSKSADSPPG
  CSGQALSLAPTPAEHGRSEVVDLTRRAGSPPGPPGAGGQLGFPGVLQGPQDGVIDLTVGH
  RARLHNVIHRALHAHVKAEREPSAAERRTCGGCRDGHCSPPAAGDPGPGAPAGPEAAAAC
  NVIVNGTRGAAAEGAKSAEPPPEQPPPPPPPAPPKKLLSPEEPAVSELESVKENNCASNC
  HLDGEAAKKLMGEEALAGGDKSDPNLNNPADEDHAYALRMLPKTGCVIQPVPKPAEKAAM
  APCIISSPMLSAGPEDLEPPLKRRCLRIRNQNK
• Function: Implicated in development of the cochlea.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[1]
Intellectual disability, anterior maxillary protrusion, and strabismus	DISK54JI	Supportive	Autosomal recessive	[3]
Syndromic intellectual disability	DISH7SDF	Limited	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sine oculis-binding protein homolog (SOBP).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sine oculis-binding protein homolog (SOBP).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sine oculis-binding protein homolog (SOBP).	[18]

14 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 Sine oculis-binding protein homolog (SOBP).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sine oculis-binding protein homolog (SOBP).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sine oculis-binding protein homolog (SOBP).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sine oculis-binding protein homolog (SOBP).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sine oculis-binding protein homolog (SOBP).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sine oculis-binding protein homolog (SOBP).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sine oculis-binding protein homolog (SOBP).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sine oculis-binding protein homolog (SOBP).	[13]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Sine oculis-binding protein homolog (SOBP).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Sine oculis-binding protein homolog (SOBP).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Sine oculis-binding protein homolog (SOBP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sine oculis-binding protein homolog (SOBP).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sine oculis-binding protein homolog (SOBP).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Sine oculis-binding protein homolog (SOBP).	[20]

References

• [1] SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system. Am J Hum Genet. 2010 Nov 12;87(5):694-700. doi: 10.1016/j.ajhg.2010.10.005. Epub 2010 Oct 28.
• [2] Recurrent intragenic exon rearrangements of SOBP and AUTS2 in non-Hodgkin B-cell lymphoma.Int J Hematol. 2020 Jan;111(1):75-83. doi: 10.1007/s12185-019-02766-z. Epub 2019 Nov 4.
• [3] Autosomal recessive mental retardation syndrome with anterior maxillary protrusion and strabismus: MRAMS syndrome. Am J Med Genet A. 2007 Aug 1;143A(15):1687-91. doi: 10.1002/ajmg.a.31810.
• [4] 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.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [17] 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.
• [18] 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.
• [19] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [20] 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.