Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZDD7EI)

• DOT Name: Uroplakin-3a
• Synonyms: UP3a; Uroplakin III; UPIII
• Gene Name: UPK3A
• Related Disease:
  Renal agenesis, unilateral
  Congenital anomaly of kidney and urinary tract
  Renal dysplasia
• UniProt ID: UPK3A_HUMAN
• Sequence:
  MPPLWALLALGCLRFGSAVNLQPQLASVTFATNNPTLTTVALEKPLCMFDSKEALTGTHE
  VYLYVLVDSAISRNASVQDSTNTPLGSTFLQTEGGRTGPYKAVAFDLIPCSDLPSLDAIG
  DVSKASQILNAYLVRVGANGTCLWDPNFQGLCNAPLSAATEYRFKYVLVNMSTGLVEDQT
  LWSDPIRTNQLTPYSTIDTWPGRRSGGMIVITSILGSLPFFLLVGFAGAIALSLVDMGSS
  DGETTHDSQITQEAVPKSLGASESSYTSVNRGPPLDRAEVYSSKLQD
• Function: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence.
• Tissue Specificity: Expressed in ureter.
• KEGG Pathway: Bladder cancer (hsa05219)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Renal agenesis, unilateral	DIS53ZJ8	Supportive	Autosomal dominant	[1]
Congenital anomaly of kidney and urinary tract	DIS84IVH	Disputed	Autosomal dominant	[2]
Renal dysplasia	DIS3DFGD	Limited	Autosomal dominant	[3]

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 Uroplakin-3a.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Uroplakin-3a.	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Uroplakin-3a.	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Uroplakin-3a.	[6]
Capecitabine	DMTS85L	Approved	Capecitabine increases the expression of Uroplakin-3a.	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Uroplakin-3a.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Uroplakin-3a.	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Uroplakin-3a.	[9]

References

• [1] De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure. J Am Soc Nephrol. 2005 Jul;16(7):2141-9. doi: 10.1681/ASN.2004090776. Epub 2005 May 11.
• [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] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.