Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV45MAS)

• DOT Name: Myelin transcription factor 1-like protein (MYT1L)
• Synonyms: MyT1-L; MyT1L
• Gene Name: MYT1L
• Related Disease:
  Syndromic intellectual disability
  Advanced cancer
  Atrial septal defect
  Autism
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Depression
  Fibromyalgia
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Intellectual disability
  Intellectual disability, autosomal dominant 39
  Lentivirus infection
  Major depressive disorder
  Neoplasm
  Neurodevelopmental disorder
  Obesity
  Precancerous condition
  Stomach cancer
  Adult glioblastoma
  Atopic dermatitis
  Psoriasis
  Schizophrenia
• UniProt ID: MYT1L_HUMAN
• Pfam ID: PF08474 ; PF01530
• Sequence:
  MEVDTEEKRHRTRSKGVRVPVEPAIQELFSCPTPGCDGSGHVSGKYARHRSVYGCPLAKK
  RKTQDKQPQEPAPKRKPFAVKADSSSVDECDDSDGTEDMDEKEEDEGEEYSEDNDEPGDE
  DEEDEEGDREEEEEIEEEDEDDDEDGEDVEDEEEEEEEEEEEEEEEENEDHQMNCHNTRI
  MQDTEKDDNNNDEYDNYDELVAKSLLNLGKIAEDAAYRARTESEMNSNTSNSLEDDSDKN
  ENLGRKSELSLDLDSDVVRETVDSLKLLAQGHGVVLSENMNDRNYADSMSQQDSRNMNYV
  MLGKPMNNGLMEKMVEESDEEVCLSSLECLRNQCFDLARKLSETNPQERNPQQNMNIRQH
  VRPEEDFPGRTPDRNYSDMLNLMRLEEQLSPRSRVFASCAKEDGCHERDDDTTSVNSDRS
  EEVFDMTKGNLTLLEKAIALETERAKAMREKMAMEAGRRDNMRSYEDQSPRQLPGEDRKP
  KSSDSHVKKPYYGKDPSRTEKKESKCPTPGCDGTGHVTGLYPHHRSLSGCPHKDRVPPEI
  LAMHESVLKCPTPGCTGRGHVNSNRNSHRSLSGCPIAAAEKLAKAQEKHQSCDVSKSSQA
  SDRVLRPMCFVKQLEIPQYGYRNNVPTTTPRSNLAKELEKYSKTSFEYNSYDNHTYGKRA
  IAPKVQTRDISPKGYDDAKRYCKDPSPSSSSTSSYAPSSSSNLSCGGGSSASSTCSKSSF
  DYTHDMEAAHMAATAILNLSTRCREMPQNLSTKPQDLCATRNPDMEVDENGTLDLSMNKQ
  RPRDSCCPILTPLEPMSPQQQAVMNNRCFQLGEGDCWDLPVDYTKMKPRRIDEDESKDIT
  PEDLDPFQEALEERRYPGEVTIPSPKPKYPQCKESKKDLITLSGCPLADKSIRSMLATSS
  QELKCPTPGCDGSGHITGNYASHRSLSGCPRAKKSGIRIAQSKEDKEDQEPIRCPVPGCD
  GQGHITGKYASHRSASGCPLAAKRQKDGYLNGSQFSWKSVKTEGMSCPTPGCDGSGHVSG
  SFLTHRSLSGCPRATSAMKKAKLSGEQMLTIKQRASNGIENDEEIKQLDEEIKELNESNS
  QMEADMIKLRTQITTMESNLKTIEEENKVIEQQNESLLHELANLSQSLIHSLANIQLPHM
  DPINEQNFDAYVTTLTEMYTNQDRYQSPENKALLENIKQAVRGIQV
• Function: Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation. In contrast to other transcription repressors that inhibit specific lineages, mediates repression of multiple differentiation programs. Also represses expression of negative regulators of neurogenesis, such as members of the Notch signaling pathway, including HES1. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Directly binds the 5'-AAGTT-3' core motif present on the promoter of target genes and represses transcription by recruiting a multiprotein complex containing SIN3B. The 5'-AAGTT-3' core motif is absent from the promoter of neural genes.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Atrial septal defect	DISJT76B	Strong	Biomarker	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Depression	DIS3XJ69	Strong	Altered Expression	[6]
Fibromyalgia	DISZJDS2	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Intellectual disability	DISMBNXP	Strong	Biomarker	[11]
Intellectual disability, autosomal dominant 39	DISETUSS	Strong	Autosomal dominant	[12]
Lentivirus infection	DISX17PY	Strong	Biomarker	[13]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Genetic Variation	[11]
Precancerous condition	DISV06FL	Strong	Biomarker	[10]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[8]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[9]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[17]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[17]
Schizophrenia	DISSRV2N	Limited	Biomarker	[14]

3 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 Myelin transcription factor 1-like protein (MYT1L).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Myelin transcription factor 1-like protein (MYT1L).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Myelin transcription factor 1-like protein (MYT1L).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myelin transcription factor 1-like protein (MYT1L).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Myelin transcription factor 1-like protein (MYT1L).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Myelin transcription factor 1-like protein (MYT1L).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin transcription factor 1-like protein (MYT1L).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Myelin transcription factor 1-like protein (MYT1L).	[25]
Manganese	DMKT129	Investigative	Manganese increases the expression of Myelin transcription factor 1-like protein (MYT1L).	[26]

References

• [1] 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.
• [2] Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.Neuropsychopharmacology. 2017 Dec;42(13):2516-2526. doi: 10.1038/npp.2017.91. Epub 2017 May 4.
• [3] CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors.Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4468-77. doi: 10.1073/pnas.1405266111. Epub 2014 Oct 7.
• [4] Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism.Psychiatr Genet. 2012 Jun;22(3):137-40. doi: 10.1097/YPG.0b013e32834dc3f5.
• [5] Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression.Biochim Biophys Acta Gene Regul Mech. 2018 Nov;1861(11):983-995. doi: 10.1016/j.bbagrm.2018.10.005. Epub 2018 Oct 10.
• [6] Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination.Neurosci Bull. 2018 Apr;34(2):247-260. doi: 10.1007/s12264-018-0207-9. Epub 2018 Feb 3.
• [7] Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system.Pain. 2014 Jun;155(6):1102-1109. doi: 10.1016/j.pain.2014.02.016. Epub 2014 Feb 26.
• [8] Clinical significance of MYT1L gene polymorphisms in Chinese patients with gastric cancer.PLoS One. 2013 Aug 28;8(8):e71979. doi: 10.1371/journal.pone.0071979. eCollection 2013.
• [9] Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors.J Cell Biochem. 2018 Jun;119(6):4644-4655. doi: 10.1002/jcb.26636. Epub 2018 Mar 9.
• [10] From the Cover: Neutralization of terminal differentiation in gliomagenesis.Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14520-7. doi: 10.1073/pnas.1308610110. Epub 2013 Aug 5.
• [11] MYT1L mutation in a patient causes intellectual disability and early onset of obesity: a case report and review of the literature.J Pediatr Endocrinol Metab. 2019 Apr 24;32(4):409-413. doi: 10.1515/jpem-2018-0505.
• [12] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [13] Myt1l induced direct reprogramming of pericytes into cholinergic neurons.CNS Neurosci Ther. 2018 Sep;24(9):801-809. doi: 10.1111/cns.12821. Epub 2018 Feb 17.
• [14] Association study of myelin transcription factor 1-like polymorphisms with schizophrenia in Han Chinese population.Genes Brain Behav. 2012 Feb;11(1):87-93. doi: 10.1111/j.1601-183X.2011.00734.x. Epub 2011 Oct 19.
• [15] The crucial role of DNA-dependent protein kinase and myelin transcription factor 1-like protein in the miR-141 tumor suppressor network.Cell Cycle. 2019 Nov;18(21):2876-2892. doi: 10.1080/15384101.2019.1652033. Epub 2019 Sep 16.
• [16] Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
• [17] Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms.Am J Hum Genet. 2015 Jan 8;96(1):104-20. doi: 10.1016/j.ajhg.2014.12.004.
• [18] 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.
• [19] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [20] 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.
• [21] 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.
• [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.
• [23] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [24] 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.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [26] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.