Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ670WI)

• DOT Name: Dymeclin (DYM)
• Synonyms: Dyggve-Melchior-Clausen syndrome protein
• Gene Name: DYM
• Related Disease:
  Angelman syndrome
  Crohn disease
  Dyggve-Melchior-Clausen disease
  Abdominal aortic aneurysm
  Alzheimer disease
  Aural atresia, congenital
  Breast cancer
  Breast carcinoma
  Bronchopulmonary dysplasia
  Cardiovascular disease
  Chronic kidney disease
  Dementia
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  High blood pressure
  Hyperlipidemia
  Intellectual disability
  Moyamoya disease
  Obstructive sleep apnea
  Prostate cancer
  Prostate carcinoma
  Pulmonary disease
  Schizophrenia
  Smith-McCort dysplasia 1
  Spondyloepimetaphyseal dysplasia
  Sweetener
  Synovial sarcoma
  Advanced cancer
  Cardiac disease
  Cornelia de Lange syndrome
  Osteochondrodysplasia
  Smith-McCort dysplasia
  Arterial disorder
  Asthma
  Coronary heart disease
  Isolated congenital microcephaly
  Neuroblastoma
  Patent ductus arteriosus
  Psychotic disorder
  Type-1/2 diabetes
• UniProt ID: DYM_HUMAN
• Pfam ID: PF09742
• Sequence:
  MGSNSSRIGDLPKNEYLKKLSGTESISENDPFWNQLLSFSFPAPTSSSELKLLEEATISV
  CRSLVENNPRTGNLGALIKVFLSRTKELKLSAECQNHIFIWQTHNALFIICCLLKVFICQ
  MSEEELQLHFTYEEKSPGNYSSDSEDLLEELLCCLMQLITDIPLLDITYEISVEAISTMV
  VFLSCQLFHKEVLRQSISHKYLMRGPCLPYTSKLVKTLLYNFIRQEKPPPPGAHVFPQQS
  DGGGLLYGLASGVATGLWTVFTLGGVGSKAAASPELSSPLANQSLLLLLVLANLTDASDA
  PNPYRQAIMSFKNTQDSSPFPSSIPHAFQINFNSLYTALCEQQTSDQATLLLYTLLHQNS
  NIRTYMLARTDMENLVLPILEILYHVEERNSHHVYMALIILLILTEDDGFNRSIHEVILK
  NITWYSERVLTEISLGSLLILVVIRTIQYNMTRTRDKYLHTNCLAALANMSAQFRSLHQY
  AAQRIISLFSLLSKKHNKVLEQATQSLRGSLSSNDVPLPDYAQDLNVIEEVIRMMLEIIN
  SCLTNSLHHNPNLVYALLYKRDLFEQFRTHPSFQDIMQNIDLVISFFSSRLLQAGAELSV
  ERVLEIIKQGVVALPKDRLKKFPELKFKYVEEEQPEEFFIPYVWSLVYNSAVGLYWNPQD
  IQLFTMDSD
• Function: Necessary for correct organization of Golgi apparatus. Involved in bone development.
• Tissue Specificity: Expressed in most embryo-fetal and adult tissues. Abundant in primary chondrocytes, osteoblasts, cerebellum, kidney, lung, stomach, heart, pancreas and fetal brain. Very low or no expression in the spleen, thymus, esophagus, bladder and thyroid gland.

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Definitive	Genetic Variation	[1]
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[2]
Dyggve-Melchior-Clausen disease	DISLC4FL	Definitive	Autosomal recessive	[3]
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Aural atresia, congenital	DISCP7UV	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[10]
Dementia	DISXL1WY	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
High blood pressure	DISY2OHH	Strong	Biomarker	[15]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[16]
Intellectual disability	DISMBNXP	Strong	Biomarker	[17]
Moyamoya disease	DISO62CA	Strong	Biomarker	[18]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Pulmonary disease	DIS6060I	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Biomarker	[21]
Smith-McCort dysplasia 1	DIS8072R	Strong	Autosomal recessive	[3]
Spondyloepimetaphyseal dysplasia	DISO4L5A	Strong	Biomarker	[22]
Sweetener	DISDGALM	Strong	Biomarker	[23]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[23]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[24]
Cardiac disease	DISVO1I5	moderate	Biomarker	[25]
Cornelia de Lange syndrome	DISEQSXO	moderate	Biomarker	[26]
Osteochondrodysplasia	DIS9SPWW	moderate	Genetic Variation	[3]
Smith-McCort dysplasia	DIS18P12	Supportive	Autosomal recessive	[27]
Arterial disorder	DISLG4XS	Disputed	Genetic Variation	[28]
Asthma	DISW9QNS	Limited	Biomarker	[4]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[29]
Isolated congenital microcephaly	DISUXHZ6	Limited	Biomarker	[22]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[30]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[31]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[21]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[25]

11 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 Dymeclin (DYM).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dymeclin (DYM).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dymeclin (DYM).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dymeclin (DYM).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dymeclin (DYM).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dymeclin (DYM).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dymeclin (DYM).	[38]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Dymeclin (DYM).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dymeclin (DYM).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dymeclin (DYM).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dymeclin (DYM).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dymeclin (DYM).	[39]

References

• [1] Case report: Angelman syndrome in an individual with a small SMC(15) and paternal uniparental disomy: a case report with reference to the assessment of cognitive functioning and autistic symptomatology.J Autism Dev Disord. 2003 Apr;33(2):171-6. doi: 10.1023/a:1022991410822.
• [2] Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.Ann Hum Genet. 2010 Nov;74(6):489-97. doi: 10.1111/j.1469-1809.2010.00606.x. Epub 2010 Sep 15.
• [3] Mental retardation and abnormal skeletal development (Dyggve-Melchior-Clausen dysplasia) due to mutations in a novel, evolutionarily conserved gene. Am J Hum Genet. 2003 Feb;72(2):419-28. doi: 10.1086/346176. Epub 2002 Dec 16.
• [4] IgE Aggravates the Senescence of Smooth Muscle Cells in Abdominal Aortic Aneurysm by Upregulating LincRNA-p21.Aging Dis. 2019 Aug 1;10(4):699-710. doi: 10.14336/AD.2018.1128. eCollection 2019 Aug.
• [5] Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes.Neuroimage Clin. 2019;23:101859. doi: 10.1016/j.nicl.2019.101859. Epub 2019 May 13.
• [6] Effects of anoxia and hypoxia on amyloid precursor protein processing in cerebral microvascular smooth muscle cells.J Neuropathol Exp Neurol. 2006 Jun;65(6):610-20. doi: 10.1097/00005072-200606000-00009.
• [7] Loss of p27(kip1) expression is associated with poor prognosis in patients with taxane-treated breast cancer.Pathol Res Pract. 2018 Apr;214(4):565-571. doi: 10.1016/j.prp.2018.02.004. Epub 2018 Feb 14.
• [8] Wnt signaling regulates smooth muscle precursor development in the mouse lung via a tenascin C/PDGFR pathway.J Clin Invest. 2009 Sep;119(9):2538-49. doi: 10.1172/JCI38079. Epub 2009 Aug 17.
• [9] PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a.J Clin Invest. 2005 Nov;115(11):3228-38. doi: 10.1172/JCI22756.
• [10] Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells.JCI Insight. 2016 Nov 3;1(18):e88646. doi: 10.1172/jci.insight.88646.
• [11] Association between childhood socioeconomic status and subjective memory complaints among older adults: results from the Japan Gerontological Evaluation Study 2010.Int Psychogeriatr. 2019 Dec;31(12):1699-1707. doi: 10.1017/S1041610219000814. Epub 2019 Jul 18.
• [12] Proteasome mediated degradation of CDC25C and Cyclin B1 in Demethoxycurcumin treated human glioma U87 MG cells to trigger G2/M cell cycle arrest.Toxicol Appl Pharmacol. 2018 Oct 1;356:76-89. doi: 10.1016/j.taap.2018.07.012. Epub 2018 Aug 4.
• [13] Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.Nucleic Acids Res. 2019 Mar 18;47(5):2455-2471. doi: 10.1093/nar/gkz052.
• [14] Silencing non-SMC chromosome-associated polypeptide G inhibits proliferation and induces apoptosis in hepatocellular carcinoma cells.Can J Physiol Pharmacol. 2018 Dec;96(12):1246-1254. doi: 10.1139/cjpp-2018-0195. Epub 2018 Aug 8.
• [15] Chemerin stimulates aortic smooth muscle cell proliferation and migration via activation of autophagy in VSMCs of metabolic hypertension rats.Am J Transl Res. 2019 Mar 15;11(3):1327-1342. eCollection 2019.
• [16] Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation.Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):764-777. doi: 10.1016/j.bbadis.2017.12.027. Epub 2017 Dec 20.
• [17] Additional three patients with Smith-McCort dysplasia due to novel RAB33B mutations.Am J Med Genet A. 2017 Mar;173(3):588-595. doi: 10.1002/ajmg.a.38064. Epub 2017 Jan 27.
• [18] Human arterial smooth muscle cell strains derived from patients with moyamoya disease: changes in biological characteristics and proliferative response during cellular aging in vitro.Mech Ageing Dev. 1994 Jul;75(1):21-33. doi: 10.1016/0047-6374(94)90025-6.
• [19] Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea.Biomed Res Int. 2019 Jun 27;2019:9174218. doi: 10.1155/2019/9174218. eCollection 2019.
• [20] Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties.J Cell Physiol. 2018 Dec;233(12):9247-9260. doi: 10.1002/jcp.27029. Epub 2018 Aug 4.
• [21] Unwell in hospital but not incapable: cross-sectional study on the dissociation of decision-making capacity for treatment and research in in-patients with schizophrenia and related psychoses.Br J Psychiatry. 2018 Aug;213(2):484-489. doi: 10.1192/bjp.2018.85. Epub 2018 Jun 18.
• [22] Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans.Hum Mol Genet. 2015 May 15;24(10):2771-83. doi: 10.1093/hmg/ddv038. Epub 2015 Feb 4.
• [23] Influence of TGF-1 expression in endothelial cells on smooth muscle cell phenotypes and MMP production under shear stress in a co-culture model.Cytotechnology. 2019 Apr;71(2):489-496. doi: 10.1007/s10616-018-0268-7. Epub 2019 Feb 1.
• [24] Taking cohesin and condensin in context.PLoS Genet. 2018 Jan 25;14(1):e1007118. doi: 10.1371/journal.pgen.1007118. eCollection 2018 Jan.
• [25] Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: a new aspect in therapy of cardiovascular diseases.Curr Vasc Pharmacol. 2013 Jul;11(4):465-79. doi: 10.2174/1570161111311040010.
• [26] Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA.Hum Mol Genet. 2009 Feb 1;18(3):418-27. doi: 10.1093/hmg/ddn369. Epub 2008 Nov 7.
• [27] Recent advances in Dyggve-Melchior-Clausen syndrome. Mol Genet Metab. 2004 Sep-Oct;83(1-2):51-9. doi: 10.1016/j.ymgme.2004.08.012.
• [28] Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Nat Genet. 2006 Mar;38(3):343-9. doi: 10.1038/ng1721. Epub 2006 Jan 29.
• [29] Counteractive effects of omentin-1 against atherogenesis?"Watanabe K. Konii H
• [30] Incorporation of high-dose (131)I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study.J Hematol Oncol. 2017 May 16;10(1):108. doi: 10.1186/s13045-017-0477-0.
• [31] Oxygen-sensitive Kv channel gene transfer confers oxygen responsiveness to preterm rabbit and remodeled human ductus arteriosus: implications for infants with patent ductus arteriosus.Circulation. 2004 Sep 14;110(11):1372-9. doi: 10.1161/01.CIR.0000141292.28616.65. Epub 2004 Sep 7.
• [32] 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.
• [33] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [34] 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.
• [35] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [36] 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.
• [37] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [38] 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.
• [39] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [40] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [41] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [42] 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.
• [43] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.