Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVRFX49)

• DOT Name: Sperm acrosome-associated protein 9 (SPACA9)
• Gene Name: SPACA9
• Related Disease:
  Alcohol use disorder
  Advanced cancer
  Cystic fibrosis
  Gonorrhea
  Prostate cancer
  Prostate carcinoma
  Alcohol dependence
  Breast cancer
  Breast carcinoma
  Autism
  Immune system disorder
• UniProt ID: SACA9_HUMAN
• PDB ID: 7UN1; 7UNG; 8J07
• Pfam ID: PF15120
• Sequence:
  MNEVKESLRSIEQKYKLFQQQQLTFTAALEHCRENAHDKIRPISSIGQVQSYMEHYCNSS
  TDRRVLLMFLDICSELNKLCQHFEAVHSGTPVTNNLLEKCKTLVSQSNDLSSLRAKYPHD
  VVNHLSCDEARNHYGGVVSLIPLILDLMKEWIAHSEKLPRKVLQHVSEPQAHQESTRGAA
  RPAQAIGTQPRATKHKCRQLTKASLKPRGCSKPPWRPPGGKL
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated spermatozoa. Forms both spirals and striations within ciliary microtubules. May stabilize the protofilaments to which they are bound.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol use disorder	DISMB65Y	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[3]
Gonorrhea	DISQ5AO6	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[6]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[7]
Autism	DISV4V1Z	Limited	Biomarker	[8]
Immune system disorder	DISAEGPH	Limited	Genetic Variation	[8]

2 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 Sperm acrosome-associated protein 9 (SPACA9).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sperm acrosome-associated protein 9 (SPACA9).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[11]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sperm acrosome-associated protein 9 (SPACA9).	[16]

References

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• [2] Evaluation of a telehealth psychological support intervention for people with primary brain tumour and their family members: Study protocol for a randomised controlled trial.Eur J Cancer Care (Engl). 2019 Jul;28(4):e13132. doi: 10.1111/ecc.13132. Epub 2019 Jul 10.
• [3] Epidemiology of Burkholderia cepacia complex colonisation in cystic fibrosis patients.Eur Respir J. 2004 Jun;23(6):851-6. doi: 10.1183/09031936.04.00118804.
• [4] Increase in Gonorrhea Incidence Associated With Enhanced Partner Notification Strategy.Sex Transm Dis. 2019 Nov;46(11):706-712. doi: 10.1097/OLQ.0000000000001060.
• [5] Entering an era of radiogenomics in prostate cancer risk stratification.Transl Androl Urol. 2018 Sep;7(Suppl 4):S443-S452. doi: 10.21037/tau.2018.07.04.
• [6] Occurrence of alcohol addiction in the adult population living in rural areas.Ann Agric Environ Med. 2018 Dec 20;25(4):659-664. doi: 10.26444/aaem/80796. Epub 2018 Jan 9.
• [7] MAST2 and NOTCH1 translocations in breast carcinoma and associated pre-invasive lesions.Hum Pathol. 2013 Dec;44(12):2837-44. doi: 10.1016/j.humpath.2013.08.001. Epub 2013 Oct 18.
• [8] Mathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in Autism.Comput Math Methods Med. 2019 Nov 11;2019:7308197. doi: 10.1155/2019/7308197. eCollection 2019.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.