Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 14C (TMEM14C)
• Gene Name: TMEM14C
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: TM14C_HUMAN
• PDB ID: 2LOS
• Pfam ID: PF03647
• Sequence:
  MQDTGSVVPLHWFGFGYAALVASGGIIGYVKAGSVPSLAAGLLFGSLAGLGAYQLSQDPR
  NVWVFLATSGTLAGIMGMRFYHSGKFMPAGLIAGASLLMVAKVGVSMFNRPH
• Function: Required for normal heme biosynthesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]

8 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 14C (TMEM14C).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transmembrane protein 14C (TMEM14C).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 14C (TMEM14C).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 14C (TMEM14C).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transmembrane protein 14C (TMEM14C).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 14C (TMEM14C).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Transmembrane protein 14C (TMEM14C).	[9]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Transmembrane protein 14C (TMEM14C).	[10]

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 14C (TMEM14C).	[7]

References

• [1] A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation.Breast Cancer Res. 2015 Jan 9;17:4. doi: 10.1186/s13058-014-0510-y.
• [2] 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.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [10] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.