Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0V91PK)

• DOT Name: Cytosolic iron-sulfur assembly component 3 (CIAO3)
• Synonyms: Cytosolic Fe-S cluster assembly factor NARFL; Iron-only hydrogenase-like protein 1; IOP1; Nuclear prelamin A recognition factor-like protein; Protein related to Narf
• Gene Name: CIAO3
• Related Disease:
  Angle-closure glaucoma
  OPTN-related open angle glaucoma
  Primary angle-closure glaucoma
  Advanced cancer
  Age-related macular degeneration
  Anxiety
  Anxiety disorder
  Central retinal vein occlusion
  Dementia
  Depression
  Diabetic macular edema
  Histoplasmosis
  Rheumatoid arthritis
  rubella
  Glycogen storage disease type II
  Obsolete pulmonary arteriovenous malformation
• UniProt ID: CIAO3_HUMAN
• Pfam ID: PF02906 ; PF02256
• Sequence:
  MASPFSGALQLTDLDDFIGPSQECIKPVKVEKRAGSGVAKIRIEDDGSYFQINQDGGTRR
  LEKAKVSLNDCLACSGCITSAETVLITQQSHEELKKVLDANKMAAPSQQRLVVVSVSPQS
  RASLAARFQLNPTDTARKLTSFFKKIGVHFVFDTAFSRHFSLLESQREFVRRFRGQADCR
  QALPLLASACPGWICYAEKTHGSFILPHISTARSPQQVMGSLVKDFFAQQQHLTPDKIYH
  VTVMPCYDKKLEASRPDFFNQEHQTRDVDCVLTTGEVFRLLEEEGVSLPDLEPAPLDSLC
  SGASAEEPTSHRGGGSGGYLEHVFRHAARELFGIHVAEVTYKPLRNKDFQEVTLEKEGQV
  LLHFAMAYGFRNIQNLVQRLKRGRCPYHYVEVMACPSGCLNGGGQLQAPDRPSRELLQHV
  ERLYGMVRAEAPEDAPGVQELYTHWLQGTDSECAGRLLHTQYHAVEKASTGLGIRW
• Function: Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. Seems to negatively regulate the level of HIF1A expression, although this effect could be indirect.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angle-closure glaucoma	DISZ95KY	Definitive	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[1]
Primary angle-closure glaucoma	DISX8UKZ	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Altered Expression	[3]
Anxiety	DISIJDBA	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Central retinal vein occlusion	DIS5ICKE	Strong	Biomarker	[5]
Dementia	DISXL1WY	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Diabetic macular edema	DIS162FN	Strong	Biomarker	[6]
Histoplasmosis	DISGTF4W	Strong	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[8]
rubella	DISXUI9P	Strong	Biomarker	[9]
Glycogen storage disease type II	DISXZPBC	moderate	Altered Expression	[3]
Obsolete pulmonary arteriovenous malformation	DISHZL6S	Limited	Autosomal recessive	[10]

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 Cytosolic iron-sulfur assembly component 3 (CIAO3).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Cytosolic iron-sulfur assembly component 3 (CIAO3).	[12]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytosolic iron-sulfur assembly component 3 (CIAO3).	[13]

References

• [1] Comparison of self-measured diurnal intraocular pressure profiles using rebound tonometry between primary angle closure glaucoma and primary open angle glaucoma patients.PLoS One. 2017 Mar 23;12(3):e0173905. doi: 10.1371/journal.pone.0173905. eCollection 2017.
• [2] Quality of end-of-life care in patients with dementia compared to patients with cancer: A population-based register study.PLoS One. 2018 Jul 30;13(7):e0201051. doi: 10.1371/journal.pone.0201051. eCollection 2018.
• [3] Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial.Br J Ophthalmol. 2018 Apr;102(4):460-464. doi: 10.1136/bjophthalmol-2017-310822. Epub 2017 Aug 4.
• [4] Opioid use before and after completion of an online pain management program.J Consult Clin Psychol. 2019 Oct;87(10):904-917. doi: 10.1037/ccp0000407.
• [5] Pre-treatment clinical features in central retinal vein occlusion that predict visual outcome following intravitreal ranibizumab.BMC Ophthalmol. 2018 Feb 9;18(1):37. doi: 10.1186/s12886-018-0701-x.
• [6] Choroidal thickness changes stratified by outcome in real-world treatment of diabetic macular edema.Graefes Arch Clin Exp Ophthalmol. 2018 Oct;256(10):1857-1865. doi: 10.1007/s00417-018-4072-z. Epub 2018 Jul 23.
• [7] PRN Ranibizumab in the Treatment of Choroidal Neovascularization Secondary to Ocular Histoplasmosis.Ophthalmic Surg Lasers Imaging Retina. 2018 Jan 1;49(1):20-26. doi: 10.3928/23258160-20171215-03.
• [8] Treat to target approach for asthma.J Asthma. 2020 Jun;57(6):687-690. doi: 10.1080/02770903.2019.1591443. Epub 2019 Mar 23.
• [9] Antibody persistence in children aged 6-7years one year following booster immunization with two MMR vaccines applied by aerosol or by injection.Vaccine. 2017 May 25;35(23):3116-3122. doi: 10.1016/j.vaccine.2017.04.027. Epub 2017 Apr 28.
• [10] A novel mutation in nuclear prelamin a recognition factor-like causes diffuse pulmonary arteriovenous malformations. Oncotarget. 2017 Jan 10;8(2):2708-2718. doi: 10.18632/oncotarget.13156.
• [11] 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.
• [12] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [13] 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.