Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc finger protein 408
• Synonyms: PR domain zinc finger protein 17
• Gene Name: ZNF408
• Related Disease:
  Exudative vitreoretinopathy 6
  Retinitis pigmentosa 72
  Retinitis pigmentosa
• UniProt ID: ZN408_HUMAN
• Pfam ID: PF21549 ; PF00096
• Sequence:
  MEEAEELLLEGKKALQLAREPRLGLDLGWNPSGEGCTQGLKDVPPEPTRDILALKSLPRG
  LALGPSLAKEQRLGVWCVGDPLQPGLLWGPLEEESASKEKGEGVKPRQEENLSLGPWGDV
  CACEQSSGWTSLVQRGRLESEGNVAPVRISERLHLQVYQLVLPGSELLLWPQPSSEGPSL
  TQPGLDKEAAVAVVTEVESAVQQEVASPGEDAAEPCIDPGSQSPSGIQAENMVSPGLKFP
  TQDRISKDSQPLGPLLQDGDVDEECPAQAQMPPELQSNSATQQDPDGSGASFSSSARGTQ
  PHGYLAKKLHSPSDQCPPRAKTPEPGAQQSGFPTLSRSPPGPAGSSPKQGRRYRCGECGK
  AFLQLCHLKKHAFVHTGHKPFLCTECGKSYSSEESFKAHMLGHRGVRPFPCPQCDKAYGT
  QRDLKEHQVVHSGARPFACDQCGKAFARRPSLRLHRKTHQVPAAPAPCPCPVCGRPLANQ
  GSLRNHMRLHTGEKPFLCPHCGRAFRQRGNLRGHLRLHTGERPYRCPHCADAFPQLPELR
  RHLISHTGEAHLCPVCGKALRDPHTLRAHERLHSGERPFPCPQCGRAYTLATKLRRHLKS
  HLEDKPYRCPTCGMGYTLPQSLRRHQLSHRPEAPCSPPSVPSAASEPTVVLLQAEPQLLD
  THREEEVSPARDVVEVTISESQEKCFVVPEEPDAAPSLVLIHKDMGLGAWAEVVEVEMGT
• Function: May be involved in transcriptional regulation.
• Tissue Specificity: Highest expression is observed in adult retina; abundantly expressed in the fetal eye . In the retina, it is detected in the outer nuclear layer, especially cone and rod photoreceptor cells, ganglion cell layer and both outer and inner plexiform layers (at protein level) . Expressed in retinal blood vessels (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Exudative vitreoretinopathy 6	DISBU6L6	Strong	Autosomal dominant	[1]
Retinitis pigmentosa 72	DISSKGAD	Strong	Autosomal recessive	[2]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein 408.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger protein 408.	[5]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Zinc finger protein 408.	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc finger protein 408.	[7]

References

• [1] Mutation spectrum of the FZD-4, TSPAN12 AND ZNF408 genes in Indian FEVR patients. BMC Ophthalmol. 2016 Jun 17;16:90. doi: 10.1186/s12886-016-0236-y.
• [2] Exome sequencing confirms ZNF408 mutations as a cause of familial retinitis pigmentosa. Ophthalmic Genet. 2017 Sep-Oct;38(5):494-497. doi: 10.1080/13816810.2016.1275020. Epub 2017 Jan 17.
• [3] Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations. Hum Mol Genet. 2015 Jul 15;24(14):4037-48. doi: 10.1093/hmg/ddv140. Epub 2015 Apr 16.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [7] 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.