Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2AN3VH)

• DOT Name: Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9)
• Synonyms: Human embryonic lung protein; HuEL; Solute carrier family 30 member 9; Zinc transporter 9; ZnT-9
• Gene Name: SLC30A9
• Related Disease: Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome
• UniProt ID: ZNT9_HUMAN
• PDB ID: 2ENK
• Pfam ID: PF01545
• Sequence:
  MLPGLAAAAAHRCSWSSLCRLRLRCRAAACNPSDRQEWQNLVTFGSFSNMVPCSHPYIGT
  LSQVKLYSTNVQKEGQGSQTLRVEKVPSFETAEGIGTELKAPLKQEPLQVRVKAVLKKRE
  YGSKYTQNNFITGVRAINEFCLKSSDLEQLRKIRRRSPHEDTESFTVYLRSDVEAKSLEV
  WGSPEALAREKKLRKEAEIEYRERLFRNQKILREYRDFLGNTKPRSRTASVFFKGPGKVV
  MVAICINGLNCFFKFLAWIYTGSASMFSEAIHSLSDTCNQGLLALGISKSVQTPDPSHPY
  GFSNMRYISSLISGVGIFMMGAGLSWYHGVMGLLHPQPIESLLWAYCILAGSLVSEGATL
  LVAVNELRRNARAKGMSFYKYVMESRDPSTNVILLEDTAAVLGVIIAATCMGLTSITGNP
  LYDSLGSLGVGTLLGMVSAFLIYTNTEALLGRSIQPEQVQRLTELLENDPSVRAIHDVKA
  TDLGLGKVRFKAEVDFDGRVVTRSYLEKQDFDQMLQEIQEVKTPEELETFMLKHGENIID
  TLGAEVDRLEKELKKRNPEVRHVDLEIL
• Function: Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health. In nucleus, functions as a secondary coactivator for nuclear receptors by cooperating with p160 coactivators subtypes. Plays a role in transcriptional activation of Wnt-responsive genes.
• Tissue Specificity: Ubiquitously expressed in fetal and adult tissues and cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome	DISUQ5CQ	Strong	Autosomal recessive	[1]

7 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 Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[4]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Proton-coupled zinc antiporter SLC30A9, mitochondrial (SLC30A9).	[8]

References

• [1] SLC30A9 mutation affecting intracellular zinc homeostasis causes a novel cerebro-renal syndrome. Brain. 2017 Apr 1;140(4):928-939.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [6] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [7] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [8] 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.