Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGYY4NK)

• DOT Name: Unconventional myosin-XVIIIb (MYO18B)
• Gene Name: MYO18B
• Related Disease:
  Bone osteosarcoma
  Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
  Nemaline myopathy
  Atrial fibrillation
  Cardiomyopathy
  Klippel-Feil syndrome 1, autosomal dominant
  Lung carcinoma
  Medulloblastoma
  Neoplasm
  Osteosarcoma
  Ovarian cancer
  Schizophrenia
  Familial atrial fibrillation
  Lung cancer
  Mesothelioma
  Acute myelogenous leukaemia
  Colorectal carcinoma
  Hepatocellular carcinoma
  Lung neoplasm
  Malignant pleural mesothelioma
  Myopathy
  Rheumatoid arthritis
  Small-cell lung cancer
• UniProt ID: MY18B_HUMAN
• Pfam ID: PF00063
• Sequence:
  MAISSRLALWEQKIREEDKSPPPSSPPPLFSVIPGGFIKQLVRGTEKEAKEARQRKQLAV
  ASPEREIPEISISQPNSKSSSGTRSGSQQISQDDQSSSPGSSDILGKESEGSRSPDPEQM
  TSINGEKAQELGSSATPTKKTVPFKRGVRRGDVLLMVAKLDPDSAKPEKTHPHDAPPCKT
  SPPATDTGKEKKGETSRTPCGSQASTEILAPKAEKTRTGGLGDPGQGTVALKKGEEGQSI
  VGKGLGTPKTTELKEAEPQGKDRQGTRPQAQGPGEGVRPGKAEKEGAEPTNTVEKGNVSK
  DVGSEGKHVRPQIPGRKWGGFLGRRSKWDGPQNKKDKEGVLLSKAEKTGEPQTQMEKTSQ
  VQGELGDDLRMGEKAGELRSTTGKAGESWDKKEKMGQPQGKSGNAGEARSQTEKGCEAPK
  EVSTMVESPAAPGKGGWPGSRGQEAEEPCSRAGDGAGALETELEGPSQPALEKDAERPRI
  RKENQDGPAPQEEGKGGQSRDSDQAPEDRWYEAEKVWLAQKDGFTLATVLKPDEGTADLP
  AGRVRLWIDADKTITEVDEEHVHRANPPELDQVEDLASLISVNESSVLNTLLQRYKAQLL
  HTCTGPDLIVLQPRGPSVPSAGKVPKGRRDGLPAHIGSMAQRAYWALLNQRRDQSIVALG
  WSGAGKTTCCEQVLEHLVGMAGSVDGRVSVEKIRATFTVLRAFGSVSMAHSRSATRFSMV
  MSLDFNATGRITAAQLQTMLLEKSRVARQPEGESNFLVFSQMLAGLDLDLRTELNLHQMA
  DSSSFGMGVWSKPEDKQKAAAAFAQLQGAMEMLGISESEQRAVWRVLAAIYHLGAAGACK
  VGRKQFMRFEWANYAAEALGCEYEELNTATFKHHLRQIIQQMTFGPSRWGLEDEETSSGL
  KMTGVDCVEGMASGLYQELFAAVVSLINRSFSSHHLSMASIMVVDSPGFQNPRHQGKDRA
  ATFEELCHNYAHERLQLLFYQRTFVSTLQRYQEEGVPVQFDLPDPSPGTTVAVVDQNPSQ
  VRLPAGGGAQDARGLFWVLDEEVHVEGSSDSVVLERLCAAFEKKGAGTEGSSALRTCEQP
  LQCEIFHQLGWDPVRYDLTGWLHRAKPNLSALDAPQVLHQSKREELRSLFQARAKLPPVC
  RAVAGLEGTSQQALQRSRMVRRTFASSLAAVRRKAPCSQIKLQMDALTSMIKRSRLHFIH
  CLVPNPVVESRSGQESPPPPQPGRDKPGAGGPLALDIPALRVQLAGFHILEALRLHRTGY
  ADHMGLTRFRRQFQVLDAPLLKKLMSTSEGIDERKAVEELLETLDLEKKAVAVGHSQVFL
  KAGVISRLEKQREKLVSQSIVLFQAACKGFLSRQEFKKLKIRRLAAQCIQKNVAVFLAVK
  DWPWWQLLGSLQPLLSATIGTEQLRAKEEELTTLRRKLEKSEKLRNELRQNTDLLESKIA
  DLTSDLADERFKGDVACQVLESERAERLQAFREVQELKSKHEQVQKKLGDVNKQLEEAQQ
  KIQLNDLERNPTGGADEWQMRFDCAQMENEFLRKRLQQCEERLDSELTARKELEQKLGEL
  QSAYDGAKKMAHQLKRKCHHLTCDLEDTCVLLENQQSRNHELEKKQKKFDLQLAQALGES
  VFEKGLREKVTQENTSVRWELGQLQQQLKQKEQEASQLKQQVEMLQDHKRELLGSPSLGE
  NCVAGLKERLWKLESSALEQQKIQSQQENTIKQLEQLRQRFELEIERMKQMHQKDREDQE
  EELEDVRQSCQKRLHQLEMQLEQEYEEKQMVLHEKQDLEGLIGTLCDQIGHRDFDVEKRL
  RRDLRRTHALLSDVQLLLGTMEDGKTSVSKEELEKVHSQLEQSEAKCEEALKTQKVLTAD
  LESMHSELENMTRNKSLVDEQLYRLQFEKADLLKRIDEDQDDLNELMQKHKDLIAQSAAD
  IGQIQELQLQLEEAKKEKHKLQEQLQVAQMRIEYLEQSTVDRAIVSRQEAVICDLENKTE
  FQKVQIKRFEVLVIRLRDSLIKMGEELSQAATSESQQRESSQYYQRRLEELKADMEELVQ
  REAEASRRCMELEKYVEELAAVRQTLQTDLETSIRRIADLQAALEEVASSDSDTESVQTA
  VDCGSSGRKEMDNVSILSSQPEGSLQSWLSCTLSLATDTMRTPSRQSATSSRILSPRINE
  EAGDTERTQSALALSRARSTNVHSKTSGDKPVSPHFVRRQKYCHFGDGEVLAVQRKSTER
  LEPASSPLASRSTNTSPLSREKLPSPSAALSEFVEGLRRKRAQRGQGSTLGLEDWPTLPI
  YQTTGASTLRRGRAGSDEGNLSLRVGAKSPLEIEGAAGGLLRSTSLKCISSDGVGGTTLL
  PEKSKTQFSSCESLLESRPSMGRKLSSPTTPRDMLLSPTLRPRRRCLESSVDDAGCPDLG
  KEPLVFQNRQFAHLMEEPLGSDPFSWKLPSLDYERKTKVDFDDFLPAIRKPQTPTSLAGS
  AKGGQDGSQRSSIHFETEEANRSFLSGIKTILKKSPEPKEDPAHLSDSSSSSGSIVSFKS
  ADSIKSRPGIPRLAGDGGERTSPERREPGTGRKDDDVASIMKKYLQK
• Function: May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth.
• Tissue Specificity: Selectively expressed in cardiac and skeletal muscles. Weakly expressed in testis, pancreas, placenta, prostate, lung and thymus.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	DISNU34U	Definitive	Autosomal recessive	[2]
Nemaline myopathy	DIS5IYLY	Definitive	Genetic Variation	[3]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[4]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[3]
Klippel-Feil syndrome 1, autosomal dominant	DISKGBD8	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[6]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[9]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[4]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[6]
Mesothelioma	DISKWK9M	moderate	Altered Expression	[10]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[7]
Lung neoplasm	DISVARNB	Limited	Genetic Variation	[13]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[10]
Myopathy	DISOWG27	Limited	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[15]
Small-cell lung cancer	DISK3LZD	Limited	Altered Expression	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Unconventional myosin-XVIIIb (MYO18B).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Unconventional myosin-XVIIIb (MYO18B).	[22]

5 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 Unconventional myosin-XVIIIb (MYO18B).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Unconventional myosin-XVIIIb (MYO18B).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Unconventional myosin-XVIIIb (MYO18B).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Unconventional myosin-XVIIIb (MYO18B).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Unconventional myosin-XVIIIb (MYO18B).	[21]

References

• [1] Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles.Curr Biol. 2019 Jan 7;29(1):81-92.e5. doi: 10.1016/j.cub.2018.11.045. Epub 2018 Dec 20.
• [2] Novel truncating mutations of MYO18B causing congenital myopathy in a Swiss patient. Neurol Genet. 2020 Jun 9;6(4):e458. doi: 10.1212/NXG.0000000000000458. eCollection 2020 Aug.
• [3] A Zebrafish Model for a Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B.Genetics. 2017 Feb;205(2):725-735. doi: 10.1534/genetics.116.192864. Epub 2016 Nov 22.
• [4] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [5] Expanding the clinical history associated with syndromic Klippel-Feil: A unique case of comorbidity with medulloblastoma.Eur J Med Genet. 2019 Aug;62(8):103701. doi: 10.1016/j.ejmg.2019.103701. Epub 2019 Jun 10.
• [6] Characterization of germline mutations in familial lung cancer from the Chinese population.Gene. 2018 Jan 30;641:94-104. doi: 10.1016/j.gene.2017.10.020. Epub 2017 Oct 17.
• [7] MYO18B promotes hepatocellular carcinoma progression by activating PI3K/AKT/mTOR signaling pathway.Diagn Pathol. 2018 Nov 3;13(1):85. doi: 10.1186/s13000-018-0763-3.
• [8] Reduced expression of MYO18B, a candidate tumor-suppressor gene on chromosome arm 22q, in ovarian cancer.Int J Cancer. 2004 Oct 20;112(1):150-4. doi: 10.1002/ijc.20339.
• [9] Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.Nature. 2009 Aug 6;460(7256):748-52. doi: 10.1038/nature08185. Epub 2009 Jul 1.
• [10] Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice.Oncol Res. 2006;16(5):235-43. doi: 10.3727/000000006783981062.
• [11] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [12] Genetic and epigenetic alterations of the candidate tumor-suppressor gene MYO18B, on chromosome arm 22q, in colorectal cancer.Genes Chromosomes Cancer. 2005 Jun;43(2):162-71. doi: 10.1002/gcc.20180.
• [13] MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer.Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12269-74. doi: 10.1073/pnas.192445899. Epub 2002 Sep 3.
• [14] Myo18b is essential for sarcomere assembly in fast skeletal muscle.Hum Mol Genet. 2017 Mar 15;26(6):1146-1156. doi: 10.1093/hmg/ddx025.
• [15] miR?60 regulates skeletal muscle proliferation in rheumatoid arthritis by targeting Myo18b.Mol Med Rep. 2019 Dec;20(6):4843-4854. doi: 10.3892/mmr.2019.10775. Epub 2019 Oct 29.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [22] 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.