Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9NOC9B)

• DOT Name: Trimeric intracellular cation channel type B (TMEM38B)
• Synonyms: TRIC-B; TRICB; Transmembrane protein 38B
• Gene Name: TMEM38B
• Related Disease:
  Osteogenesis imperfecta
  Osteogenesis imperfecta type 14
  Osteogenesis imperfecta type 4
• UniProt ID: TM38B_HUMAN
• Pfam ID: PF05197
• Sequence:
  MDSPWDELALAFSRTSMFPFFDIAHYLVSVMAVKRQPGAAALAWKNPISSWFTAMLHCFG
  GGILSCLLLAEPPLKFLANHTNILLASSIWYITFFCPHDLVSQGYSYLPVQLLASGMKEV
  TRTWKIVGGVTHANSYYKNGWIVMIAIGWARGAGGTIITNFERLVKGDWKPEGDEWLKMS
  YPAKVTLLGSVIFTFQHTQHLAISKHNLMFLYTIFIVATKITMMTTQTSTMTFAPFEDTL
  SWMLFGWQQPFSSCEKKSEAKSPSNGVGSLASKPVDVASDNVKKKHTKKNE
• Function: Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[1]
Osteogenesis imperfecta type 14	DISL6DKB	Strong	Autosomal recessive	[2]
Osteogenesis imperfecta type 4	DIS8S46L	Supportive	Autosomal dominant	[3]

15 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 Trimeric intracellular cation channel type B (TMEM38B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Trimeric intracellular cation channel type B (TMEM38B).	[16]

References

• [1] Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.J Clin Endocrinol Metab. 2017 Jun 1;102(6):2019-2028. doi: 10.1210/jc.2016-3766.
• [2] TRIC channels are essential for Ca2+ handling in intracellular stores. Nature. 2007 Jul 5;448(7149):78-82. doi: 10.1038/nature05928.
• [3] Aurora-B overexpression is correlated with aneuploidy and poor prognosis in non-small cell lung cancer. Lung Cancer. 2013 Apr;80(1):85-90. doi: 10.1016/j.lungcan.2012.12.018. Epub 2013 Jan 11.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.