Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLP76WE)

• DOT Name: Transmembrane protein 126A (TMEM126A)
• Gene Name: TMEM126A
• Related Disease:
  Auditory neuropathy
  Autosomal recessive optic atrophy, OPA7 type
  Breast cancer
  Breast carcinoma
• UniProt ID: T126A_HUMAN
• Pfam ID: PF07114
• Sequence:
  MENHKSNNKENITIVDISRKINQLPEAERNLLENGSVYVGLNAALCGLIANSLFRRILNV
  TKARIAAGLPMAGIPFLTTDLTYRCFVSFPLNTGDLDCETCTITRSGLTGLVIGGLYPVF
  LAIPVNGGLAARYQSALLPHKGNILSYWIRTSKPVFRKMLFPILLQTMFSAYLGSEQYKL
  LIKALQLSEPGKEIH
• Tissue Specificity: Strongly expressed in brain, cerebellum, skeletal muscle, testis. High expression also found in fetal brain, fetal retinal pigmentary epithelium, and fetal retina. Highly expressed in retinal ganglion cells.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Auditory neuropathy	DISM6GAU	Definitive	Biomarker	[1]
Autosomal recessive optic atrophy, OPA7 type	DIS5KBOT	Strong	Autosomal recessive	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transmembrane protein 126A (TMEM126A).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 126A (TMEM126A).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 126A (TMEM126A).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transmembrane protein 126A (TMEM126A).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 126A (TMEM126A).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 126A (TMEM126A).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 126A (TMEM126A).	[10]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Transmembrane protein 126A (TMEM126A).	[11]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Transmembrane protein 126A (TMEM126A).	[12]

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 decreases the methylation of Transmembrane protein 126A (TMEM126A).	[8]

References

• [1] Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy.Mol Vis. 2010 Apr 13;16:650-64.
• [2] TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy. Am J Hum Genet. 2009 Apr;84(4):493-8. doi: 10.1016/j.ajhg.2009.03.003. Epub 2009 Mar 26.
• [3] Loss of TMEM126A promotes extracellular matrix remodeling, epithelial-to-mesenchymal transition, and breast cancer metastasis by regulating mitochondrial retrograde signaling.Cancer Lett. 2019 Jan;440-441:189-201. doi: 10.1016/j.canlet.2018.10.018. Epub 2018 Oct 26.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [12] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.