Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT576F40)

• DOT Name: Neurite extension and migration factor (NEXMIF)
• Synonyms: XLMR protein related to neurite extension; XPN
• Gene Name: NEXMIF
• Related Disease:
  Intellectual disability
  X-linked complex neurodevelopmental disorder
  Epilepsy
  LennoxGastaut syndrome
  Neurodevelopmental disorder
  X-linked intellectual disability
  X-linked intellectual disability, Cantagrel type
  Myoclonic-astatic epilepsy
  Autism spectrum disorder
  Pervasive developmental disorder
• UniProt ID: NEXMI_HUMAN
• Pfam ID: PF15735
• Sequence:
  MDNQQDKAIVASANGENTLINGVKENDSEDQDVAMKSFAALEAAAPIQPTPVAQKETLMY
  PRGLLPLPSKKPCMQSPPSPLGLIEAPEHAANSASVNAISLTSGIAKGLNTWSLPNECEK
  APFAIMEPAGMSALNGDCLMQPSRTCLGCFMESKDAVDPEPGISLKVGDLNRDYETCAVS
  DIGIQCINAGENMKYGEQLLSDQLLGFPLHKSRAGDRRETEKPDIDLEDPAQKSYYEALL
  LDKCNTEEALLANSNQDWGYFETFISESKIELLDLCSKNELSVNLFSEEDVDNYMFDDDE
  STLGSDVCSLKIRYESFQDNVRDKTTLLMQEDAQFNFFPSVFTTCPKRESKSGALKQSSD
  FSQFKVPDVSIIWGEEDKNLDKKKGKEEGQEDKGVEKKDGKDNGEKPALNKPCSGTEVEQ
  LKNPKQGHLANSLETSGSFSDDSSFIEISYDAMGEIKDCSRYMARDTNSGSSSSQQNYGL
  RAKRKVRYSEDYLYDVDSLEGEKVNERKEWLPVGSKEEDDDEWCPKKRRKVTRKEPPVII
  KYIIINRFKGEKNMLVKLGKVDASETTVNLSENQLNKYAKLAPLKGFWQKKKKQRNTNTD
  SIKTPFSQKQSFEPGSFEVSFLPPARKRKSKLGNRHRIQRIPSIEISASSKQISLCNDQR
  HASNHKEDGGLKGTLKSAPLGAPSCANGSHLNDITGPDSVKVKAQDTEFKGPERKVLNKI
  KFKSEARLKSKKVKAAGQESKPIVQMSPLLENQSSKANLKNEVIPGTSNSSRLSEFHEAK
  AAKSSTFLPTTCSSEMPLSSANVTTNIPVIPGGYLQTLLDASDLSNNTSISYFSHHSPEQ
  NEGSLTQTEKSFVPLQPTQDCVLTSSSDSELQQSSHNFKMESSNYRNVWPNKATSGTQEF
  MAEVSREIAPTQSSEFGASQVVSMENNLTPTTYNPICLNSGGSNCNKVLYDSMQDTQLPS
  DDSYQLCHFNNGEICFPFQQGPVNMDDGRLFSFDSMAPLSVSSSNYCSLSLKSCEKDGDD
  DITDDFLAHCSPKLVIQQSIDEIAPLKESTDLLDISNFTPDKFRHSSLSEMSPPDTPSLS
  PQITRCESMKTLGTLKGFQEGVPGPLDSVEKIKWDCSTLSRQVQMEDGFTLNNHQFQFHM
  FNDEDSVSLLQKNPCLSTFNDPSGQISTNNKVSKSRKKSSPSKSGAMNQSSSQKNTRKKS
  LKGNNKGIEKPPGKNSRQVPKSTKKGKYMAAINGEKMQIGIGRGGSQTNTISSTGKTLAE
  CIQHGGPMASMKMPSQKGLSGDWALGKESSPGWSDMSMGTNTNSLLDDDQREFQEPSYIL
  SNIASGMADVQRFMMASIEPLWEPMEHHGDPNIFYSPESNSLKLKTLKILAGTPQESKKK
  INSGSQGATKNHRSIKGVSKSNGKTAIGDPGRANMPGYNEDSRSTFFDKKYSNMSTLGNN
  GPTHKKLYRHKSSSKALRDEKCKGKHMEREQVHKDESGTASFEKLRDSDYNLLKAETTFW
  VLPVFEEETRIFQKDI
• Function: Involved in neurite outgrowth by regulating cell-cell adhesion via the N-cadherin signaling pathway. May act by regulating expression of protein-coding genes, such as N-cadherins and integrin beta-1 (ITGB1).
• Tissue Specificity: Highly expressed in fetal and adult brain, predominantly in the cerebral cortex and the cerebellum. Also expressed in other tissues but to a lesser extent.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Biomarker	[1]
X-linked complex neurodevelopmental disorder	DISI3QE9	Definitive	X-linked	[2]
Epilepsy	DISBB28L	Strong	Biomarker	[3]
LennoxGastaut syndrome	DISOTGO5	Strong	Genetic Variation	[4]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[1]
X-linked intellectual disability	DISYJBY3	Strong	Biomarker	[5]
X-linked intellectual disability, Cantagrel type	DISP424V	Strong	X-linked	[6]
Myoclonic-astatic epilepsy	DISTAVMU	Supportive	Unknown	[7]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[8]
Pervasive developmental disorder	DIS51975	Limited	Biomarker	[8]

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 Neurite extension and migration factor (NEXMIF).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neurite extension and migration factor (NEXMIF).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neurite extension and migration factor (NEXMIF).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Neurite extension and migration factor (NEXMIF).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neurite extension and migration factor (NEXMIF).	[13]

References

• [1] NEXMIF/KIDLIA Knock-out Mouse Demonstrates Autism-Like Behaviors, Memory Deficits, and Impairments in Synapse Formation and Function.J Neurosci. 2020 Jan 2;40(1):237-254. doi: 10.1523/JNEUROSCI.0222-19.2019. Epub 2019 Nov 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] De novo variants in neurodevelopmental disorders with epilepsy.Nat Genet. 2018 Jul;50(7):1048-1053. doi: 10.1038/s41588-018-0143-7. Epub 2018 Jun 25.
• [4] Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability.JAMA Neurol. 2017 Nov 1;74(11):1301-1311. doi: 10.1001/jamaneurol.2017.1775.
• [5] Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. J Med Genet. 2004 Oct;41(10):736-42. doi: 10.1136/jmg.2004.021626.
• [6] NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns. Genet Med. 2021 Feb;23(2):363-373. doi: 10.1038/s41436-020-00988-9. Epub 2020 Nov 4.
• [7] Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020 May;61(5):995-1007. doi: 10.1111/epi.16508. Epub 2020 May 29.
• [8] Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother.J Hum Genet. 2018 Jul;63(7):847-850. doi: 10.1038/s10038-018-0459-2. Epub 2018 May 1.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] 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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.