Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNX7GD4)

• DOT Name: Centrosome and spindle pole-associated protein 1 (CSPP1)
• Gene Name: CSPP1
• Related Disease:
  Joubert syndrome 21
  Ciliopathy
  Epithelial ovarian cancer
  Jeune syndrome
  Nephronophthisis
  Ovarian cancer
  Ovarian neoplasm
  Joubert syndrome
  Joubert syndrome with Jeune asphyxiating thoracic dystrophy
  Meckel syndrome
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Joubert syndrome 1
  Meckel syndrome, type 1
• UniProt ID: CSPP1_HUMAN
• Sequence:
  MLFPLQVAAVTSSVRDDPLEHCVSPRTRARSPEICKMADNLDEFIEEQKARLAEDKAELE
  SDPPYMEMKGKLSAKLSENSKILISMAKENIPPNSQQTRGSLGIDYGLSLPLGEDYERKK
  HKLKEELRQDYRRYLTQGITQGKRKKNFLSTSETDPSTLGVSLPIGERLSAKERLKLERN
  KEYNQFLRGKEESSEKFRQVEKSTEPKSQRNKKPIGQVKPDLTSQIQTSCENSEGPRKDV
  LTPSEAYEELLNQRRLEEDRYRQLDDEIELRNRRIIKKANEEVGISNLKHQRFASKAGIP
  DRRFHRFNEDRVFDRRYHRPDQDPEVSEEMDERFRYESDFDRRLSRVYTNDRMHRNKRGN
  MPPMEHDGDVIEQSNIRISSAENKSAPDNETSKSANQDTCSPFAGMLFGGEDRELIQRRK
  EKYRLELLEQMAEQQRNKRREKDLELRVAASGAQDPEKSPDRLKQFSVAPRHFEEMIPPE
  RPRIAFQTPLPPLSAPSVPPIPSVHPVPSQNEDLRSGLSSALGEMVSPRIAPLPPPPLLP
  PLATNYRTPYDDAYYFYGSRNTFDPSLAYYGSGMMGVQPAAYVSAPVTHQLAQPVVNTVG
  QNELKITSDQVINSGLIFEDKPKPSKQSLQSYQEALQQQIREREERRKKEREEKEEYEAK
  LEAEMRTYNPWGKGGGGAPLRDAKGNLITDLNRMHRQNIDAYHNPDARTYEDKRAVVSLD
  PNLATSNAENLEDAANKSSGHMQTQSSPFARGNVFGEPPTELQIKQQELYKNFLRFQIEE
  KKQREEAERERLRIAEEKEERRLAEQRARIQQEYEEEQEKKREKEEEQRLKNEEHIRLAE
  ERQKEAERKKKEEEEKYNLQLQHYCERDNLIGEETKHMRQPSPIVPALQNKIASKLQRPP
  SVDSIIRSFIHESSMSRAQSPPVPARKNQLRAEEEKKNVIMELSEMRKQLRSEERRLQER
  LLHMDSDDEIPIRKKERNPMDIFDMARHRLQAPVRRQSPKGLDAATFQNVHDFNELKDRD
  SETRVDLKFMYLDPPRDHHTLEIQQQALLREQQKRLNRIKMQEGAKVDLDAIPSAKVREQ
  RMPRDDTSDFLKNSLLESDSAFIGAYGETYPAIEDDVLPPPSQLPSARERRRNKWKGLDI
  DSSRPNVAPDGLSLKSISSVNVDELRVRNEERMRRLNEFHNKPINTDDESSLVDPDDIMK
  HIGDDGSNSVATEPWLRPGTSETLKRFMAEQLNQEQQQIPGKPGTFTWQGLSTAHG
• Function: May play a role in cell-cycle-dependent microtubule organization.
• Tissue Specificity: Expressed in adult and fetal brain with enrichment in the cerebellum. Detected in testis.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 21	DIS6DGTX	Definitive	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[3]
Jeune syndrome	DISLC357	Strong	Genetic Variation	[4]
Nephronophthisis	DISXU4HY	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[3]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[4]
Joubert syndrome with Jeune asphyxiating thoracic dystrophy	DIS0AZCT	Supportive	Autosomal recessive	[4]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[7]
Carcinoma	DISH9F1N	Limited	Altered Expression	[7]
Joubert syndrome 1	DISC9Q82	Limited	GermlineCausalMutation	[2]
Meckel syndrome, type 1	DIS4YWZU	Limited	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Centrosome and spindle pole-associated protein 1 (CSPP1) increases the response to substance of Cisplatin.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[14]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[15]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[22]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Centrosome and spindle pole-associated protein 1 (CSPP1).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Centrosome and spindle pole-associated protein 1 (CSPP1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Centrosome and spindle pole-associated protein 1 (CSPP1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Centrosome and spindle pole-associated protein 1 (CSPP1).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Centrosome and spindle pole-associated protein 1 (CSPP1).	[19]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Centrosome and spindle pole-associated protein 1 (CSPP1).	[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] Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans.Am J Hum Genet. 2014 Jan 2;94(1):73-9. doi: 10.1016/j.ajhg.2013.11.010. Epub 2013 Dec 19.
• [3] circ-CSPP1 promotes proliferation, invasion and migration of ovarian cancer cells by acting as a miR-1236-3p sponge.Biomed Pharmacother. 2019 Jun;114:108832. doi: 10.1016/j.biopha.2019.108832. Epub 2019 Apr 11.
• [4] Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. Am J Hum Genet. 2014 Jan 2;94(1):62-72. doi: 10.1016/j.ajhg.2013.11.019. Epub 2013 Dec 19.
• [5] Mutations in CSPP1 lead to classical Joubert syndrome. Am J Hum Genet. 2014 Jan 2;94(1):80-6. doi: 10.1016/j.ajhg.2013.11.015. Epub 2013 Dec 19.
• [6] 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.
• [7] Nuclear CSPP1 expression defined subtypes of basal-like breast cancer.Br J Cancer. 2014 Jul 15;111(2):326-38. doi: 10.1038/bjc.2014.297. Epub 2014 Jun 5.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] 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.
• [16] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [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] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [23] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [24] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [25] Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans. PLoS One. 2011;6(7):e21920. doi: 10.1371/journal.pone.0021920. Epub 2011 Jul 6.