Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRAK1LK)

• DOT Name: Radial spoke head protein 9 homolog (RSPH9)
• Gene Name: RSPH9
• Related Disease:
  Nasal polyp
  Primary ciliary dyskinesia 12
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Primary ciliary dyskinesia
  Carcinoma
• UniProt ID: RSPH9_HUMAN
• PDB ID: 8J07
• Sequence:
  MDADSLLLSLELASGSGQGLSPDRRASLLTSLMLVKRDYRYDRVLFWGRILGLVADYYIA
  QGLSEDQLAPRKTLYSLNCTEWSLLPPATEEMVAQSSVVKGRFMGDPSYEYEHTELQKVN
  EGEKVFEEEIVVQIKEETRLVSVIDQIDKAVAIIPRGALFKTPFGPTHVNRTFEGLSLSE
  AKKLSSYFHFREPVELKNKTLLEKADLDPSLDFMDSLEHDIPKGSWSIQMERGNALVVLR
  SLLWPGLTFYHAPRTKNYGYVYVGTGEKNMDLPFML
• Function: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia. Required for motility of olfactory and neural cilia and for the structural integrity of ciliary axonemes in both 9+0 and 9+2 motile cilia.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasal polyp	DISLP3XE	Definitive	Altered Expression	[1]
Primary ciliary dyskinesia 12	DIS7OOQT	Definitive	Autosomal recessive	[2]
Bladder cancer	DISUHNM0	Strong	Posttranslational Modification	[3]
Urinary bladder cancer	DISDV4T7	Strong	Posttranslational Modification	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Posttranslational Modification	[3]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[4]
Carcinoma	DISH9F1N	Limited	Biomarker	[5]

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 Radial spoke head protein 9 homolog (RSPH9).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Radial spoke head protein 9 homolog (RSPH9).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Radial spoke head protein 9 homolog (RSPH9).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Radial spoke head protein 9 homolog (RSPH9).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Radial spoke head protein 9 homolog (RSPH9).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Radial spoke head protein 9 homolog (RSPH9).	[9]

References

• [1] An Integrated Analysis of Radial Spoke Head and Outer Dynein Arm Protein Defects and Ciliogenesis Abnormality in Nasal Polyps.Front Genet. 2019 Nov 13;10:1083. doi: 10.3389/fgene.2019.01083. eCollection 2019.
• [2] 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.
• [3] RSPH9 methylation pattern as a prognostic indicator in patients with non-muscle invasive bladder cancer.Oncol Rep. 2016 Feb;35(2):1195-203. doi: 10.3892/or.2015.4409. Epub 2015 Nov 11.
• [4] Primary Ciliary Dyskinesia. 2007 Jan 24 [updated 2019 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [5] High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.J Neuropathol Exp Neurol. 2015 Feb;74(2):110-20. doi: 10.1097/NEN.0000000000000154.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.