Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTII3FTO)

• DOT Name: LEM domain-containing protein 1 (LEMD1)
• Synonyms: Cancer/testis antigen 50; CT50; LEM domain protein 1; LEMP-1
• Gene Name: LEMD1
• Related Disease:
  Benign prostatic hyperplasia
  Colorectal neoplasm
  Gastric cancer
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Testicular cancer
  Advanced cancer
  Carcinoma
  Neoplasm
  Squamous cell carcinoma
• UniProt ID: LEMD1_HUMAN
• Pfam ID: PF03020
• Sequence:
  MVDVKCLSDCKLQNQLEKLGFSPGPILPSTRKLYEKKLVQLLVSPPCAPPVMNGPRELDG
  AQDSDDSEELNIILQGNIILSTEKSKKLKKWPEASTTKRKAVDTYCLDYKPSKGRRWAAR
  APSTRITYGTITKERDYCAEDQTIESWREEGFPVGLKLAVLGIFIIVVFVYLTVENKSLF
  G
• Tissue Specificity: Testis-specific. Isoform 6 is detected in 17 of 18 colon cancer tissues examined.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Carcinoma	DISH9F1N	Limited	Biomarker	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[5]

11 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 LEM domain-containing protein 1 (LEMD1).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of LEM domain-containing protein 1 (LEMD1).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of LEM domain-containing protein 1 (LEMD1).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of LEM domain-containing protein 1 (LEMD1).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of LEM domain-containing protein 1 (LEMD1).	[10]
Malathion	DMXZ84M	Approved	Malathion increases the expression of LEM domain-containing protein 1 (LEMD1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of LEM domain-containing protein 1 (LEMD1).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of LEM domain-containing protein 1 (LEMD1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of LEM domain-containing protein 1 (LEMD1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of LEM domain-containing protein 1 (LEMD1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of LEM domain-containing protein 1 (LEMD1).	[17]

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 LEM domain-containing protein 1 (LEMD1).	[14]

References

• [1] Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer.Arch Med Res. 2010 Apr;41(3):195-200. doi: 10.1016/j.arcmed.2010.04.003.
• [2] Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in colorectal cancers.Oncol Rep. 2004 Aug;12(2):275-80.
• [3] LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer.J Cell Biochem. 2019 Sep;120(9):15190-15201. doi: 10.1002/jcb.28783. Epub 2019 Apr 25.
• [4] Identification and functional analysis of variants of a cancer/testis antigen LEMD1 in colorectal cancer stem-like cells.Biochem Biophys Res Commun. 2017 Apr 8;485(3):651-657. doi: 10.1016/j.bbrc.2017.02.081. Epub 2017 Feb 20.
• [5] LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration.Br J Cancer. 2016 Jun 28;115(1):52-8. doi: 10.1038/bjc.2016.167. Epub 2016 Jun 9.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [9] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] 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.
• [13] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [14] 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.
• [15] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.