Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50LI46)

• DOT Name: Transmembrane protein 229B (TMEM229B)
• Gene Name: TMEM229B
• Related Disease:
  Chronic kidney disease
  Chronic renal failure
  Parkinson disease
• UniProt ID: T229B_HUMAN
• Pfam ID: PF06541
• Sequence:
  MASAEPLTALSRWYLYAIHGYFCEVMFTAAWEFVVNLNWKFPGVTSVWALFIYGTSILIV
  ERMYLRLRGRCPLLLRCLIYTLWTYLWEFTTGFILRQFNACPWDYSQFDFDFMGLITLEY
  AVPWFCGALIMEQFIIRNTLRLRFDKDAEPGEPSGALALANGHVKTD

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 229B (TMEM229B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 229B (TMEM229B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transmembrane protein 229B (TMEM229B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 229B (TMEM229B).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transmembrane protein 229B (TMEM229B).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 229B (TMEM229B).	[9]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Transmembrane protein 229B (TMEM229B).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 229B (TMEM229B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 229B (TMEM229B).	[8]

References

• [1] Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms.J Am Soc Nephrol. 2018 May;29(5):1513-1524. doi: 10.1681/ASN.2017101099. Epub 2018 Mar 15.
• [2] A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [6] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [11] 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.