Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZXGVJ9)

• DOT Name: Intraflagellar transport-associated protein (IFTAP)
• Synonyms: Protein HEPIS
• Gene Name: IFTAP
• Related Disease:
  Non-alcoholic fatty liver disease
  Seasonal allergic rhinitis
• UniProt ID: IFTAP_HUMAN
• Pfam ID: PF17722
• Sequence:
  MSAHMSGLEIMDEDQLIKDVLDKFLNCHEQTYDEEFLNTFTHLSQEDHVSKRGVFGTDSS
  ENIFTSAKVTHKNEADDYHLRNKTIFLRTSSQCLEEQVDNFLDLEDLDMDEEIKPQMSED
  LLLLPGEVEQDVSTSIPSCIPFVAQPPTCEVKPKPSVKRMDKQTEEILGDEVQLFSLDEE
  FDYDNVMLTSKFSPAEIENIKELCKQQKRKDTSPDLEKSCD
• Function: Seems to play a role in ciliary BBSome localization, maybe through interaction with IFT-A complex.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[1]
Seasonal allergic rhinitis	DIS58KQX	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Intraflagellar transport-associated protein (IFTAP).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Intraflagellar transport-associated protein (IFTAP).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Intraflagellar transport-associated protein (IFTAP).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Intraflagellar transport-associated protein (IFTAP).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Intraflagellar transport-associated protein (IFTAP).	[12]

References

• [1] Comparison of Abdominal Obesity and Fatty Liver and Their Association with Insulin Resistance and Metabolic Syndrome in Chinese Adults.Obesity (Silver Spring). 2019 May;27(5):707-715. doi: 10.1002/oby.22432. Epub 2019 Apr 3.
• [2] Effects of a Cloth Panel Containing a Specific Ore Powder on Patients with Japanese Cedar Pollen Allergy During the Pollen Dispersal Season.J Clin Med. 2019 Dec 6;8(12):2164. doi: 10.3390/jcm8122164.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.