Details of Drug Off-Target (DOT)

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

• DOT Name: Radial spoke head protein 3 homolog (RSPH3)
• Synonyms: A-kinase anchor protein RSPH3; Radial spoke head-like protein 2
• Gene Name: RSPH3
• Related Disease:
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia 32
  Primary ciliary dyskinesia
• UniProt ID: RSPH3_HUMAN
• PDB ID: 8J07
• Pfam ID: PF06098
• Sequence:
  MTVKPAKAASLARNLAKRRRTYLGGAAGRSQEPEVPCAAVLPGKPGDRNCPEFPPPDRTL
  GCWATDAAPAAGLCGAGSEPSIAPTSCAGNLPSRPPPLLSPLLASRNPCPWHYLHLSGSH
  NTLAPTCFKAKLHRKRGSQPPDMASALTDRTSRAPSTYTYTSRPRALPCQRSRYRDSLTQ
  PDEEPMHYGNIMYDRRVIRGNTYALQTGPLLGRPDSLELQRQREARKRALARKQAQEQLR
  PQTPEPVEGRKHVDVQTELYLEEIADRIIEVDMECQTDAFLDRPPTPLFIPAKTGKDVAT
  QILEGELFDFDLEVKPVLEVLVGKTIEQSLLEVMEEEELANLRASQREYEELRNSERAEV
  QRLEEQERRHREEKERRKKQQWEIMHKHNETSQKIAARAFAQRYLADLLPSVFGSLRDSG
  YFYDPIERDIEIGFLPWLMNEVEKTMEYSMVGRTVLDMLIREVVEKRLCMYEHGEDTHQS
  PEPEDEPGGPGAMTESLEASEFLEQSMSQTRELLLDGGYLQRTTYDRRSSQERKFMEERE
  LLGQDEETAMRKSLGEEELS
• Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. Functions as a protein kinase A-anchoring protein that scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a point of convergence for MAPK and PKA signaling in cilia.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[1]
Primary ciliary dyskinesia 32	DISHG9AM	Strong	Autosomal recessive	[1]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[1]

11 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 Radial spoke head protein 3 homolog (RSPH3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Radial spoke head protein 3 homolog (RSPH3).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[7]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Radial spoke head protein 3 homolog (RSPH3).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Radial spoke head protein 3 homolog (RSPH3).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Radial spoke head protein 3 homolog (RSPH3).	[12]

References

• [1] RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes. Am J Hum Genet. 2015 Jul 2;97(1):153-62. doi: 10.1016/j.ajhg.2015.05.004. Epub 2015 Jun 11.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.