Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7LSKJ)

• DOT Name: Protein rogdi homolog (ROGDI)
• Gene Name: ROGDI
• Related Disease:
  Amelocerebrohypohidrotic syndrome
  Advanced cancer
  Autism spectrum disorder
  Amelogenesis imperfecta
  Ehlers-Danlos syndrome, kyphoscoliotic and deafness type
  HSD10 mitochondrial disease
• UniProt ID: ROGDI_HUMAN
• PDB ID: 5XQH; 5XQI
• Pfam ID: PF10259
• Sequence:
  MATVMAATAAERAVLEEEFRWLLHDEVHAVLKQLQDILKEASLRFTLPGSGTEGPAKQEN
  FILGSCGTDQVKGVLTLQGDALSQADVNLKMPRNNQLLHFAFREDKQWKLQQIQDARNHV
  SQAIYLLTSRDQSYQFKTGAEVLKLMDAVMLQLTRARNRLTTPATLTLPEIAASGLTRMF
  APALPSDLLVNVYINLNKLCLTVYQLHALQPNSTKNFRPAGGAVLHSPGAMFEWGSQRLE
  VSHVHKVECVIPWLNDALVYFTVSLQLCQQLKDKISVFSSYWSYRPF
• Tissue Specificity: Widely expressed with highest levels in spinal cord, brain, heart and bone marrow. Also expressed in fetal brain and liver.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amelocerebrohypohidrotic syndrome	DIS0DATV	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Amelogenesis imperfecta	DISGYR9E	moderate	Biomarker	[4]
Ehlers-Danlos syndrome, kyphoscoliotic and deafness type	DISA74TB	Limited	Genetic Variation	[5]
HSD10 mitochondrial disease	DISCJYFW	Limited	Genetic Variation	[5]

1 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 Protein rogdi homolog (ROGDI).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein rogdi homolog (ROGDI).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein rogdi homolog (ROGDI).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein rogdi homolog (ROGDI).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein rogdi homolog (ROGDI).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Protein rogdi homolog (ROGDI).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein rogdi homolog (ROGDI).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein rogdi homolog (ROGDI).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein rogdi homolog (ROGDI).	[14]

References

• [1] 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.
• [2] Cancer risk susceptibility loci in a Swedish population.Oncotarget. 2017 Nov 25;8(66):110300-110310. doi: 10.18632/oncotarget.22687. eCollection 2017 Dec 15.
• [3] Recessive gene disruptions in autism spectrum disorder.Nat Genet. 2019 Jul;51(7):1092-1098. doi: 10.1038/s41588-019-0433-8. Epub 2019 Jun 17.
• [4] SLC13A5 is the second gene associated with Kohlschtter-T?nz syndrome. J Med Genet. 2017 Jan;54(1):54-62. doi: 10.1136/jmedgenet-2016-103988. Epub 2016 Sep 6.
• [5] Genotype-based databases for variants causing rare diseases.Gene. 2014 Oct 15;550(1):136-40. doi: 10.1016/j.gene.2014.08.016. Epub 2014 Aug 8.
• [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] 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.
• [8] 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.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] 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.
• [11] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.