Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ZNSV0)

• DOT Name: Tuftelin
• Gene Name: TUFT1
• Related Disease: Woolly hair-skin fragility syndrome
• UniProt ID: TUFT1_HUMAN
• Sequence:
  MNGTRNWCTLVDVHPEDQAAGSVDILRLTLQGELTGDELEHIAQKAGRKTYAMVSSHSAG
  HSLASELVESHDGHEEIIKVYLKGRSGDKMIHEKNINQLKSEVQYIQEARNCLQKLREDI
  SSKLDRNLGDSLHRQEIQVVLEKPNGFSQSPTALYSSPPEVDTCINEDVESLRKTVQDLL
  AKLQEAKRQHQSDCVAFEVTLSRYQREAEQSNVALQREEDRVEQKEAEVGELQRRLLGME
  TEHQALLAKVREGEVALEELRSNNADCQAEREKAATLEKEVAGLREKIHHLDDMLKSQQR
  KVRQMIEQLQNSKAVIQSKDATIQELKEKIAYLEAENLEMHDRMEHLIEKQISHGNFSTQ
  ARAKTENPGSIRISKPPSPKPMPVIRVVET
• Function: Involved in the structural organization of the epidermis. Involved in the mineralization and structural organization of enamel.
• Tissue Specificity: Expressed in the epidermis (at protein level) . Present in the extracellular enamel and is mainly associated with the crystal component.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Woolly hair-skin fragility syndrome	DISS2UEJ	Strong	Autosomal recessive	[1]

25 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 Tuftelin.	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tuftelin.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tuftelin.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tuftelin.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tuftelin.	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tuftelin.	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tuftelin.	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tuftelin.	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tuftelin.	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tuftelin.	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tuftelin.	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tuftelin.	[13]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Tuftelin.	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tuftelin.	[15]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Tuftelin.	[16]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Tuftelin.	[17]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tuftelin.	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Tuftelin.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tuftelin.	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tuftelin.	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tuftelin.	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tuftelin.	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Tuftelin.	[22]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tuftelin.	[17]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Tuftelin.	[23]

References

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• [13] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
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• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [19] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.