Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFCJ4S0)

• DOT Name: Serine/Arginine-related protein 53 (RSRC1)
• Synonyms: SRrp53; Arginine/serine-rich coiled-coil protein 1
• Gene Name: RSRC1
• Related Disease:
  Schizophrenia
  Anxiety
  Intellectual developmental disorder, autosomal recessive 70
  Intellectual disability
  Major depressive disorder
  Obesity
  Nasopharyngeal carcinoma
  Neuroblastoma
  Autosomal recessive non-syndromic intellectual disability
  Chronic obstructive pulmonary disease
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: RSRC1_HUMAN
• Sequence:
  MGRRSSDTEEESRSKRKKKHRRRSSSSSSSDSRTYSRKKGGRKSRSKSRSWSRDLQPRSH
  SYDRRRRHRSSSSSSYGSRRKRSRSRSRGRGKSYRVQRSRSKSRTRRSRSRPRLRSHSRS
  SERSSHRRTRSRSRDRERRKGRDKEKREKEKDKGKDKELHNIKRGESGNIKAGLEHLPPA
  EQAKARLQLVLEAAAKADEALKAKERNEEEAKRRKEEDQATLVEQVKRVKEIEAIESDSF
  VQQTFRSSKEVKKSVEPSEVKQATSTSGPASAVADPPSTEKEIDPTSIPTAIKYQDDNSL
  AHPNLFIEKADAEEKWFKRLIALRQERLMGSPVA
• Function: Has a role in alternative splicing and transcription regulation. Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing.
• Tissue Specificity: Widely expressed. Expressed in brain, spinal cord, cerebellum.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Genetic Variation	[2]
Intellectual developmental disorder, autosomal recessive 70	DISGLLOZ	Strong	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[6]
Neuroblastoma	DISVZBI4	moderate	Genetic Variation	[7]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[3]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[8]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/Arginine-related protein 53 (RSRC1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[14]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Serine/Arginine-related protein 53 (RSRC1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[16]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Serine/Arginine-related protein 53 (RSRC1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/Arginine-related protein 53 (RSRC1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/Arginine-related protein 53 (RSRC1).	[18]

References

• [1] RSRC1 mutation affects intellect and behaviour through aberrant splicing and transcription, downregulating IGFBP3.Brain. 2018 Apr 1;141(4):961-970. doi: 10.1093/brain/awy045.
• [2] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [3] GWAS signals revisited using human knockouts. Genet Med. 2018 Jan;20(1):64-68. doi: 10.1038/gim.2017.78. Epub 2017 Jun 22.
• [4] Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
• [5] Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.Nat Genet. 2013 May;45(5):501-12. doi: 10.1038/ng.2606. Epub 2013 Apr 7.
• [6] Discovery of recurrent structural variants in nasopharyngeal carcinoma.Genome Res. 2014 Feb;24(2):300-9. doi: 10.1101/gr.156224.113. Epub 2013 Nov 8.
• [7] RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children.Gene. 2018 Jul 1;662:83-87. doi: 10.1016/j.gene.2018.04.015. Epub 2018 Apr 10.
• [8] Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.
• [9] RSRC1 suppresses gastric cancer cell proliferation and migration by regulating PTEN expression.Mol Med Rep. 2019 Aug;20(2):1747-1753. doi: 10.3892/mmr.2019.10409. Epub 2019 Jun 21.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [13] 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.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [18] 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.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.