Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT730MMV)

• DOT Name: Protein FRA10AC1 (FRA10AC1)
• Gene Name: FRA10AC1
• Related Disease: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities
• UniProt ID: F10C1_HUMAN
• Pfam ID: PF09725
• Sequence:
  MHGHGGYDSDFSDDERCGESSKRKKRTVEDDLLLQKPFQKEKHGKVAHKQVAAELLDREE
  ARNRRFHLIAMDAYQRHTKFVNDYILYYGGKKEDFKRLGENDKTDLDVIRENHRFLWNEE
  DEMDMTWEKRLAKKYYDKLFKEYCIADLSKYKENKFGFRWRVEKEVISGKGQFFCGNKYC
  DKKEGLKSWEVNFGYIEHGEKRNALVKLRLCQECSIKLNFHHRRKEIKSKKRKDKTKKDC
  EESSHKKSRLSSAEEASKKKDKGHSSSKKSEDSLLRNSDEEESASESELWKGPLPETDEK
  SQEEEFDEYFQDLFL
• Function: May be involved in pre-mRNA splicing.
• Tissue Specificity: Ubiquitously expressed with higher expression in brain, heart, skeletal muscle, kidney and liver.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities	DIS726P5	Moderate	Autosomal recessive	[1]

8 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 Protein FRA10AC1 (FRA10AC1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FRA10AC1 (FRA10AC1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FRA10AC1 (FRA10AC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FRA10AC1 (FRA10AC1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FRA10AC1 (FRA10AC1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein FRA10AC1 (FRA10AC1).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein FRA10AC1 (FRA10AC1).	[10]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Protein FRA10AC1 (FRA10AC1).	[11]

3 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 decreases the methylation of Protein FRA10AC1 (FRA10AC1).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein FRA10AC1 (FRA10AC1).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein FRA10AC1 (FRA10AC1).	[9]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.