Details of Drug Off-Target (DOT)

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

• DOT Name: DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30)
• Synonyms: Williams-Beuren syndrome chromosomal region 18 protein
• Gene Name: DNAJC30
• Related Disease:
  Leber hereditary optic neuropathy, autosomal recessive
  Leber hereditary optic neuropathy
• UniProt ID: DJC30_HUMAN
• PDB ID: 2YUA
• Pfam ID: PF00226
• Sequence:
  MAAMRWRWWQRLLPWRLLQARGFPQNSAPSLGLGARTYSQGDCSYSRTALYDLLGVPSTA
  TQAQIKAAYYRQCFLYHPDRNSGSAEAAERFTRISQAYVVLGSATLRRKYDRGLLSDEDL
  RGPGVRPSRTPAPDPGSPRTPPPTSRTHDGSRASPGANRTMFNFDAFYQAHYGEQLERER
  RLRARREALRKRQEYRSMKGLRWEDTRDTAAIFLIFSIFIIIGFYI
• Function: Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration. Associates with the ATP synthase complex and facilitates ATP synthesis. May be a chaperone protein involved in the turnover of the subunits of mitochondrial complex I N-module. It facilitates the degradation of N-module subunits damaged by oxidative stress, and contributes to complex I functional efficiency.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, lung, spleen, stomach and testis . Highly expressed in the brain . In the neocortex, expressed in most, if not all, glutamatergic excitatory projection neurons (pyramidal) and many interneurons, with the strongest signal noticeably in large pyramidal neurons of layer 3C. Also present in pyramidal neurons of layer 3C PNs of the superior temporal cortex, as well as in pyramidal neurons (Betz cells) of the layer 5B primary motor cortex (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leber hereditary optic neuropathy, autosomal recessive	DISUNRW2	Strong	Autosomal recessive	[1]
Leber hereditary optic neuropathy	DIS7Y2EE	Supportive	Mitochondrial	[1]

5 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 DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[6]

1 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 increases the methylation of DnaJ homolog subfamily C member 30, mitochondrial (DNAJC30).	[7]

References

• [1] Impaired complex I repair causes recessive Leber's hereditary optic neuropathy. J Clin Invest. 2021 Mar 15;131(6):e138267. doi: 10.1172/JCI138267.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.