Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE2ZGFB)

• DOT Name: Tetratricopeptide repeat protein 39B (TTC39B)
• Synonyms: TPR repeat protein 39B
• Gene Name: TTC39B
• Related Disease:
  Endometriosis
  Esophageal squamous cell carcinoma
  Gallbladder disease
• UniProt ID: TT39B_HUMAN
• Pfam ID: PF10300 ; PF13181
• Sequence:
  MDAVLACRLRGRGNRVAALRPRPRPGGSAGPSPFALLCAGLSPEPRAGVGSEFPAWFLGG
  SSQRRNMALLGSRAELEADEDVFEDALETISISSHSDMATSSLHFASCDTQQAPRQRGAS
  TVSSSSSTKVDLKSGLEECAVALNLFLSNKFTDALELLRPWAKESMYHALGYSTIVVLQA
  VLTFEQQDIQNGISAMKDALQTCQKYRKKYTVVESFSSLLSRGSLEQLSEEEMHAEICYA
  ECLLQKAALTFVQDENMINFIKGGLKIRTSYQIYKECLSILHEIQKNKLQQEFFYEFEGG
  VKLGSGAFNLMLSLLPARIIRLLEFIGFSGNRELGLLQLREGASGRSMRSALCCLTILAF
  HTYISLILGTGEVNVAEAERLLAPFLQQFPNGSLVLFYHARIELLKGNLEEAQEVFQKCI
  SVQEEWKQFHHLCYWELMWINVFQQNWMQAYYYSDLLCKESKWSKATYVFLKAAILSMLP
  EEDVVATNENVVTLFRQVDSLKQRIAGKSIPTEKFAVRKARRYSASLPAPVKLILPALEM
  MYVWNGFSIVSKRKDLSENLLVTVEKAEAALQSQNFNSFSVDDECLVKLLKGCCLKNLQR
  PLQAELCYNHVVESEKLLKYDHYLVPFTLFELASLYKSQGEIDKAIKFLETARNNYKDYS
  LESRLHFRIQAALHLWRKPSSD
• Function: Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Endometriosis	DISX1AG8	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[2]
Gallbladder disease	DISA6W3T	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tetratricopeptide repeat protein 39B (TTC39B).	[15]

References

• [1] Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis.Nat Commun. 2016 Jul 25;7:12350. doi: 10.1038/ncomms12350.
• [2] BRCA2 loss-of-function germline mutations are associated with esophageal squamous cell carcinoma risk in Chinese.Int J Cancer. 2020 Feb 15;146(4):1042-1051. doi: 10.1002/ijc.32619. Epub 2019 Aug 26.
• [3] Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array.Eur J Hum Genet. 2016 Jan;24(1):106-12. doi: 10.1038/ejhg.2015.63. Epub 2015 Apr 29.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.