Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHB658P)

DOT Name	Neurotrophin-4 (NTF4)
Synonyms	NT-4; Neurotrophin-5; NT-5; Neutrophic factor 4
Gene Name	NTF4
Related Disease	Glaucoma 1, open angle, O ( )
UniProt ID	NTF4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1B8M; 1B98; 1HCF
Pfam ID	PF00243
Sequence	MLPLPSCSLPILLLFLLPSVPIESQPPPSTLPPFLAPEWDLLSPRVVLSRGAPAGPPLLF LLEAGAFRESAGAPANRSRRGVSETAPASRRGELAVCDAVSGWVTDRRTAVDLRGREVEV LGEVPAAGGSPLRQYFFETRCKADNAEEGGPGAGGGGCRGVDRRHWVSECKAKQSYVRAL TADAQGRVGWRWIRIDTACVCTLLSRTGRA
Function	Target-derived survival factor for peripheral sensory sympathetic neurons.
Tissue Specificity	Highest levels in prostate, lower levels in thymus, placenta, and skeletal muscle. Expressed in embryonic and adult tissues.
KEGG Pathway	MAPK sig.ling pathway (hsa04010 ) Ras sig.ling pathway (hsa04014 ) PI3K-Akt sig.ling pathway (hsa04151 ) Neurotrophin sig.ling pathway (hsa04722 )
Reactome Pathway	Activated NTRK2 signals through RAS (R-HSA-9026519 ) Activated NTRK2 signals through PLCG1 (R-HSA-9026527 ) Activated NTRK2 signals through PI3K (R-HSA-9028335 ) Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731 ) NTF4 activates NTRK2 (TRKB) signaling (R-HSA-9026357 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Glaucoma 1, open angle, O	DISVCH5D	Disputed	Autosomal dominant	[1]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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 Neurotrophin-4 (NTF4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Neurotrophin-4 (NTF4).	[5]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neurotrophin-4 (NTF4).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neurotrophin-4 (NTF4).	[4]
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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	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.
3	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
4	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.
5	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.