Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK7F9XZ)

• DOT Name: Nurim (NRM)
• Synonyms: Nuclear envelope membrane protein; Nuclear rim protein
• Gene Name: NRM
• Related Disease:
  Multiple sclerosis
  Acute graft versus host disease
  Acute myelogenous leukaemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Chronic graft versus host disease
  Primary myelofibrosis
  Rheumatoid arthritis
  Seminoma
• UniProt ID: NRM_HUMAN
• Sequence:
  MAPALLLIPAALASFILAFGTGVEFVRFTSLRPLLGGIPESGGPDARQGWLAALQDRSIL
  APLAWDLGLLLLFVGQHSLMAAERVKAWTSRYFGVLQRSLYVACTALALQLVMRYWEPIP
  KGPVLWEARAEPWATWVPLLCFVLHVISWLLIFSILLVFDYAELMGLKQVYYHVLGLGEP
  LALKSPRALRLFSHLRHPVCVELLTVLWVVPTLGTDRLLLAFLLTLYLGLAHGLDQQDLR
  YLRAQLQRKLHLLSRPQDGEAE

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[1]
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Chronic graft versus host disease	DIS1MM9J	Strong	Biomarker	[7]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[8]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[9]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nurim (NRM).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nurim (NRM).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nurim (NRM).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nurim (NRM).	[12]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nurim (NRM).	[13]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Nurim (NRM).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nurim (NRM).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nurim (NRM).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nurim (NRM).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nurim (NRM).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nurim (NRM).	[18]

References

• [1] SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients.Genes Immun. 2011 Oct;12(7):523-30. doi: 10.1038/gene.2011.25. Epub 2011 Jun 9.
• [2] The new refined minnesota risk score for acute graft-versus-host disease predicts overall survival and non-relapse mortality after T cell-replete haploidentical stem cell transplant with post-transplant cyclophosphamide.Bone Marrow Transplant. 2019 Jul;54(7):1164-1167. doi: 10.1038/s41409-019-0453-0. Epub 2019 Jan 24.
• [3] Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients.Biol Blood Marrow Transplant. 2019 Sep;25(9):1803-1809. doi: 10.1016/j.bbmt.2019.05.014. Epub 2019 May 22.
• [4] The integral nuclear membrane protein nurim plays a role in the suppression of apoptosis.Curr Mol Med. 2012 Dec;12(10):1372-82. doi: 10.2174/156652412803833571.
• [5] Polymorphisms in homologous recombination repair genes and the risk and survival of breast cancer.J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2988. Epub 2017 Oct 10.
• [6] Tacrolimus Concentration-to-Dose Ratios in Kidney Transplant Recipients and Relationship to Clinical Outcomes.Pharmacotherapy. 2019 Aug;39(8):827-836. doi: 10.1002/phar.2300. Epub 2019 Jul 18.
• [7] Fludarabine/busulfan versus fludarabine/total-body-irradiation (2Gy) as conditioning prior to allogeneic stem cell transplantation in patients (?0 years) with acute myelogenous leukemia: a study of the acute leukemia working party of the EBMT.Bone Marrow Transplant. 2020 Apr;55(4):729-739. doi: 10.1038/s41409-019-0720-0. Epub 2019 Oct 23.
• [8] Pulmonary hypertension is associated with increased nonrelapse mortality after allogeneic hematopoietic cell transplantation for myelofibrosis.Bone Marrow Transplant. 2020 May;55(5):877-883. doi: 10.1038/s41409-019-0741-8. Epub 2019 Nov 6.
• [9] TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.N Engl J Med. 2007 Sep 20;357(12):1199-209. doi: 10.1056/NEJMoa073491. Epub 2007 Sep 5.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] 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.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [15] 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.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.