Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7I6RBT)

• DOT Name: Required for meiotic nuclear division protein 1 homolog (RMND1)
• Gene Name: RMND1
• Related Disease:
  B-cell neoplasm
  Deafness
  Dysautonomia
  Mitochondrial disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiomyopathy
  Combined oxidative phosphorylation defect type 11
  Leukodystrophy
  Osteoporosis
  Kidney failure
  Lactic acidosis
  Neoplasm
• UniProt ID: RMND1_HUMAN
• Pfam ID: PF02582
• Sequence:
  MPATLLRAVARSHHILSKAHQCRRIGHLMLKPLKEFENTTCSTLTIRQSLDLFLPDKTAS
  GLNKSQILEMNQKKSDTSMLSPLNAARCQDEKAHLPTMKSFGTHRRVTHKPNLLGSKWFI
  KILKRHFSSVSTETFVPKQDFPQVKRPLKASRTRQPSRTNLPVLSVNEDLMHCTAFATAD
  EYHLGNLSQDLASHGYVEVTSLPRDAANILVMGVENSAKEGDPGTIFFFREGAAVFWNVK
  DKTMKHVMKVLEKHEIQPYEIALVHWENEELNYIKIEGQSKLHRGEIKLNSELDLDDAIL
  EKFAFSNALCLSVKLAIWEASLDKFIESIQSIPEALKAGKKVKLSHEEVMQKIGELFALR
  HRINLSSDFLITPDFYWDRENLEGLYDKTCQFLSIGRRVKVMNEKLQHCMELTDLMRNHL
  NEKRALRLEWMIVILITIEVMFELGRVFF
• Function: Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Biomarker	[1]
Deafness	DISKCLH4	Definitive	Genetic Variation	[2]
Dysautonomia	DISF4MT6	Definitive	Genetic Variation	[3]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[6]
Combined oxidative phosphorylation defect type 11	DISO61ZA	Strong	Autosomal recessive	[6]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[7]
Osteoporosis	DISF2JE0	Strong	Biomarker	[8]
Kidney failure	DISOVQ9P	Limited	Genetic Variation	[2]
Lactic acidosis	DISZI1ZK	Limited	Genetic Variation	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Required for meiotic nuclear division protein 1 homolog (RMND1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Required for meiotic nuclear division protein 1 homolog (RMND1).	[18]

References

• [1] Cloning and mapping of human chromosome 6q26-q27 deleted in B-cell non-Hodgkin lymphoma and multiple tumor types.Genomics. 1998 Jun 1;50(2):170-86. doi: 10.1006/geno.1998.5321.
• [2] Hearing impairment and renal failure associated with RMND1 mutations.Am J Med Genet A. 2016 Jan;170A(1):142-7. doi: 10.1002/ajmg.a.37399. Epub 2015 Sep 23.
• [3] RMND1 deficiency associated with neonatal lactic acidosis, infantile onset renal failure, deafness, and multiorgan involvement.Eur J Hum Genet. 2015 Oct;23(10):1301-7. doi: 10.1038/ejhg.2014.293. Epub 2015 Jan 21.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
• [6] Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77. doi: 10.1001/jama.2014.7184.
• [7] RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.Pediatr Neurol. 2017 Jan;66:59-62. doi: 10.1016/j.pediatrneurol.2016.09.003. Epub 2016 Sep 13.
• [8] Association of RMND1/CCDC170-ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women.Climacteric. 2019 Feb;22(1):97-104. doi: 10.1080/13697137.2018.1538339. Epub 2019 Jan 2.
• [9] The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21.Genomics. 1998 May 15;50(1):34-43. doi: 10.1006/geno.1998.5270.
• [10] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [16] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [17] 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.
• [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.