Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT37XCNP)

DOT Name	Protein misato homolog 1 (MSTO1)
Gene Name	MSTO1
Related Disease	Leishmaniasis ( ) Mitochondrial disease ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Cerebellar ataxia ( ) Colon cancer ( ) Colon carcinoma ( ) Insomnia ( ) Liver cancer ( ) Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome ( ) Muscular dystrophy ( ) Myopathy ( ) Neuromuscular disease ( ) Post-traumatic stress disorder ( ) Promyelocytic leukaemia ( ) Retinitis pigmentosa ( ) Bone osteosarcoma ( ) Brain neoplasm ( ) Congenital muscular dystrophy ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Plasma cell myeloma ( ) Rhabdomyosarcoma ( ) Acute lymphocytic leukaemia ( ) Childhood acute lymphoblastic leukemia ( ) High blood pressure ( ) Non-small-cell lung cancer ( ) T-cell acute lymphoblastic leukaemia ( ) Type-1/2 diabetes ( )
UniProt ID	MSTO1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF10644 ; PF14881
Sequence	MAGGAREVLTLQLGHFAGFVGAHWWNQQDAALGRATDSKEPPGELCPDVLYRTGRTLHGQ ETYTPRLILMDLKGSLSSLKEEGGLYRDKQLDAAIAWQGKLTTHKEELYPKNPYLQDFLS AEGVLSSDGVWRVKSIPNGKGSSPLPTATTPKPLIPTEASIRVWSDFLRVHLHPRSICMI QKYNHDGEAGRLEAFGQGESVLKEPKYQEELEDRLHFYVEECDYLQGFQILCDLHDGFSG VGAKAAELLQDEYSGRGIITWGLLPGPYHRGEAQRNIYRLLNTAFGLVHLTAHSSLVCPL SLGGSLGLRPEPPVSFPYLHYDATLPFHCSAILATALDTVTVPYRLCSSPVSMVHLADML SFCGKKVVTAGAIIPFPLAPGQSLPDSLMQFGGATPWTPLSACGEPSGTRCFAQSVVLRG IDRACHTSQLTPGTPPPSALHACTTGEEILAQYLQQQQPGVMSSSHLLLTPCRVAPPYPH LFSSCSPPGMVLDGSPKGAAVESIPVFGALCSSSSLHQTLEALARDLTKLDLRRWASFMD AGVEHDDVAELLQELQSLAQCYQGGDSLVD
Function	Involved in the regulation of mitochondrial distribution and morphology. Required for mitochondrial fusion and mitochondrial network formation.
Tissue Specificity	Present in all cell lines tested (at protein level). Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Leishmaniasis	DISABTW7	Definitive	Biomarker	[1]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[7]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Insomnia	DIS0AFR7	Strong	Biomarker	[10]
Liver cancer	DISDE4BI	Strong	Biomarker	[7]
Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome	DISY3B42	Strong	Autosomal recessive	[11]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[12]
Myopathy	DISOWG27	Strong	Genetic Variation	[8]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[11]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[10]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[13]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[8]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[14]
Brain neoplasm	DISY3EKS	moderate	Biomarker	[14]
Congenital muscular dystrophy	DISKY7OY	moderate	Genetic Variation	[15]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[14]
Pancreatic cancer	DISJC981	moderate	Biomarker	[16]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[17]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[18]
Acute lymphocytic leukaemia	DISPX75S	Limited	Genetic Variation	[19]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Genetic Variation	[19]
High blood pressure	DISY2OHH	Limited	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[21]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[19]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[20]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

6 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 Protein misato homolog 1 (MSTO1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein misato homolog 1 (MSTO1).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein misato homolog 1 (MSTO1).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein misato homolog 1 (MSTO1).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein misato homolog 1 (MSTO1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein misato homolog 1 (MSTO1).	[28]
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⏷ Show the Full List of 6 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein misato homolog 1 (MSTO1).	[27]
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References

1	Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis.Parasitol Int. 2017 Feb;66(1):884-888. doi: 10.1016/j.parint.2016.10.003. Epub 2016 Oct 8.
2	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.
3	Current state of nonengrafting donor leukocyte infusion (focus on microtransplantation for acute myeloid leukemia).Curr Opin Hematol. 2019 Nov;26(6):373-378. doi: 10.1097/MOH.0000000000000539.
4	Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation.Asian Pac J Cancer Prev. 2016;17(4):1993-8. doi: 10.7314/apjcp.2016.17.4.1993.
5	ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease.Neurorehabil Neural Repair. 2016 Oct;30(9):883-93. doi: 10.1177/1545968316642523. Epub 2016 Apr 13.
6	MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells.J Nutrigenet Nutrigenomics. 2014;7(4-6):283-98. doi: 10.1159/000381346. Epub 2015 May 27.
7	Prognostic impact of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation in patients with unresectable hepatocellular carcinoma: Comparison with TACE alone using decision-tree analysis after propensity score matching.Hepatol Res. 2019 Aug;49(8):919-928. doi: 10.1111/hepr.13348. Epub 2019 May 13.
8	Whole-exome sequencing identifies rare compound heterozygous mutations in the MSTO1 gene associated with cerebellar ataxia and myopathy.Eur J Med Genet. 2020 Jan;63(1):103623. doi: 10.1016/j.ejmg.2019.01.013. Epub 2019 Jan 24.
9	Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation.Biochem Pharmacol. 2018 Mar;149:186-204. doi: 10.1016/j.bcp.2017.10.011. Epub 2017 Oct 23.
10	Associations between traumatic brain injury from intimate partner violence and future psychosocial health risks in women.Compr Psychiatry. 2019 Jul;92:13-21. doi: 10.1016/j.comppsych.2019.05.001. Epub 2019 May 14.
11	Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia. Hum Mutat. 2017 Aug;38(8):970-977. doi: 10.1002/humu.23262. Epub 2017 Jun 6.
12	MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.Acta Neuropathol. 2019 Dec;138(6):1013-1031. doi: 10.1007/s00401-019-02059-z. Epub 2019 Aug 29.
13	MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-B pathway.Tumour Biol. 2015 Nov;36(11):8425-37. doi: 10.1007/s13277-015-3575-z. Epub 2015 May 29.
14	Targeting DNA-PKcs and telomerase in brain tumour cells.Mol Cancer. 2014 Oct 13;13:232. doi: 10.1186/1476-4598-13-232.
15	A novel case of MSTO1 gene related congenital muscular dystrophy with progressive neurological involvement.Neuromuscul Disord. 2019 Jun;29(6):448-455. doi: 10.1016/j.nmd.2019.03.011. Epub 2019 Mar 27.
16	The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.J Biol Chem. 2018 Sep 14;293(37):14455-14469. doi: 10.1074/jbc.RA118.003279. Epub 2018 Aug 2.
17	Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes.Life Sci. 2019 Jul 1;228:66-71. doi: 10.1016/j.lfs.2019.04.060. Epub 2019 Apr 25.
18	Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis.Cancer Res. 2018 Oct 1;78(19):5513-5520. doi: 10.1158/0008-5472.CAN-17-3912. Epub 2018 Aug 9.
19	Frequent deletions at 12q14.3 chromosomal locus in adult acute lymphoblastic leukemia.Genes Chromosomes Cancer. 2005 Jan;42(1):87-94. doi: 10.1002/gcc.20116.
20	Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.Aging (Albany NY). 2018 May 24;10(5):1166-1181. doi: 10.18632/aging.101459.
21	Non-surgical therapy for patients with advanced non-small cell lung cancer.Respirology. 1998 Sep;3(3):151-7. doi: 10.1111/j.1440-1843.1998.tb00114.x.
22	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
23	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.
24	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
25	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
26	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
27	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
28	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.