Details of Drug Off-Target (DOT)

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

• DOT Name: FAST kinase domain-containing protein 5, mitochondrial (FASTKD5)
• Gene Name: FASTKD5
• Related Disease: Schizophrenia
• UniProt ID: FAKD5_HUMAN
• Pfam ID: PF06743 ; PF08368 ; PF08373
• Sequence:
  MAATLKSLKLVRYRAFCSPSAFGAVRSVSYWNVSSTQHGGQDPPEHISLCHSAKKVKNIC
  STFSSRRILTTSSAHPGLEFSKTSSSKASTLQLGSPRATGVDEEDVEVFDSFENMRVFLQ
  LRPEYRVHSYNASETSQLLSVSEGELILHKVRVNQNNLQAQVIVDYLCKLSSLPAEQHPV
  LLGSTSFALLCQLSVKKIQLFDTQDLINVLKAFVILGIPHSHSMLDVYETKCCHQVWEMN
  MDQLLLVADLWRYLGRKVPRFLNIFSSYLNLHWKDLSLSQLVHLIYVIGENRQVSQDLMQ
  KLESLILKYIDLINLEEVGTICLGFFKSSTNLSEFVMRKIGDLACANIQHLSSRSLVNIV
  KMFRFTHVDHINFMKQIGEIAPQRIPSLGVQGVMHLTLYCSALRFLNEGVMNAVAASLPP
  RVAHCRSKDVAKILWSFGTLNYKPPNAEEFYSSLISEIHRKMPEFNQYPEHLPTCLLGLA
  FLEYFPVELIDFALSPGFVRLAQERTKFDLLKELYTLDGTVGIECPDYRGNRLSTHLQQE
  GSELLWYLAEKDMNSKPEFLETVFLLETMLGGPQYVKHHMILPHTRSSDLEVQLDVNLKP
  LPFNREATPAENVAKLRLEHVGVSLTDDLMNKLLKGKARGHFQGKTESEPGQQPMELENK
  AAVPLGGFLCNVADKSGAMEMAGLCPAACMQTPRMKLAVQFTNRNQYCYGSRDLLGLHNM
  KRRQLARLGYRVVELSYWEWLPLLKRTRLEKLAFLHEKVFTSAL
• Function: Plays an important role in the processing of non-canonical mitochondrial mRNA precursors.
• Tissue Specificity: Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in heart, smooth muscle, liver and thyroid.
• Reactome Pathway: FASTK family proteins regulate processing and stability of mitochondrial RNAs (R-HSA-9837092)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]

10 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 FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[10]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of FAST kinase domain-containing protein 5, mitochondrial (FASTKD5).	[11]

References

• [1] Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.