Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT590V63)

• DOT Name: Integral membrane protein 2A (ITM2A)
• Synonyms: Protein E25
• Gene Name: ITM2A
• Related Disease:
  Carcinoma
  Cleft palate
  Epithelial ovarian cancer
  Familial partial lipodystrophy, Dunnigan type
  Graves disease
  Intellectual disability
  Isolated cleft palate
  Neoplasm
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Bacterial infection
  Breast cancer
  Breast carcinoma
• UniProt ID: ITM2A_HUMAN
• Pfam ID: PF04089
• Sequence:
  MVKIAFNTPTAVQKEEARQDVEALLSRTVRTQILTGKELRVATQEKEGSSGRCMLTLLGL
  SFILAGLIVGGACIYKYFMPKSTIYRGEMCFFDSEDPANSLRGGEPNFLPVTEEADIRED
  DNIAIIDVPVPSFSDSDPAAIIHDFEKGMTAYLDLLLGNCYLMPLNTSIVMPPKNLVELF
  GKLASGRYLPQTYVVREDLVAVEEIRDVSNLGIFIYQLCNNRKSFRLRRRDLLLGFNKRA
  IDKCWKIRHFPNEFIVETKICQE

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Cleft palate	DIS6G5TF	Strong	Genetic Variation	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Familial partial lipodystrophy, Dunnigan type	DISD1N0B	Strong	Biomarker	[3]
Graves disease	DISU4KOQ	Strong	Altered Expression	[4]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Bacterial infection	DIS5QJ9S	moderate	Genetic Variation	[4]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]

19 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 Integral membrane protein 2A (ITM2A).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Integral membrane protein 2A (ITM2A).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Integral membrane protein 2A (ITM2A).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Integral membrane protein 2A (ITM2A).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Integral membrane protein 2A (ITM2A).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Integral membrane protein 2A (ITM2A).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Integral membrane protein 2A (ITM2A).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Integral membrane protein 2A (ITM2A).	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Integral membrane protein 2A (ITM2A).	[14]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Integral membrane protein 2A (ITM2A).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Integral membrane protein 2A (ITM2A).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Integral membrane protein 2A (ITM2A).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Integral membrane protein 2A (ITM2A).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Integral membrane protein 2A (ITM2A).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Integral membrane protein 2A (ITM2A).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Integral membrane protein 2A (ITM2A).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Integral membrane protein 2A (ITM2A).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Integral membrane protein 2A (ITM2A).	[22]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone affects the expression of Integral membrane protein 2A (ITM2A).	[23]

References

• [1] Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer.Gynecol Oncol. 2016 Mar;140(3):545-53. doi: 10.1016/j.ygyno.2015.12.006. Epub 2015 Dec 12.
• [2] A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency.BMC Med Genet. 2015 Sep 1;16:74. doi: 10.1186/s12881-015-0220-z.
• [3] Itm2a silencing rescues lamin A mediated inhibition of 3T3-L1 adipocyte differentiation.Adipocyte. 2017 Oct 2;6(4):259-276. doi: 10.1080/21623945.2017.1362510. Epub 2017 Sep 5.
• [4] ITM2A Expands Evidence for Genetic and Environmental Interaction in Graves Disease Pathogenesis.J Clin Endocrinol Metab. 2017 Feb 1;102(2):652-660. doi: 10.1210/jc.2016-2625.
• [5] Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction.Cell Commun Signal. 2019 Aug 22;17(1):105. doi: 10.1186/s12964-019-0422-7.
• [6] Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions.J Mol Med (Berl). 2012 Oct;90(10):1185-95. doi: 10.1007/s00109-012-0895-y. Epub 2012 Apr 21.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [9] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
• [10] Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology. 2015 Feb 3;328:102-11. doi: 10.1016/j.tox.2014.12.018. Epub 2014 Dec 18.
• [11] 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.
• [12] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [15] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [16] 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.
• [17] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [18] 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.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [23] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.