Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTADS8G3)

• DOT Name: Fascin-2 (FSCN2)
• Synonyms: Retinal fascin
• Gene Name: FSCN2
• Related Disease:
  Age-related macular degeneration
  Macular degeneration
  Retinitis pigmentosa 17
  Retinitis pigmentosa
  Retinitis pigmentosa 30
• UniProt ID: FSCN2_HUMAN
• Pfam ID: PF06268
• Sequence:
  MPTNGLHQVLKIQFGLVNDTDRYLTAESFGFKVNASAPSLKRKQTWVLEPDPGQGTAVLL
  RSSHLGRYLSAEEDGRVACEAEQPGRDCRFLVLPQPDGRWVLRSEPHGRFFGGTEDQLSC
  FATAVSPAELWTVHLAIHPQAHLLSVSRRRYVHLCPREDEMAADGDKPWGVDALLTLIFR
  SRRYCLKSCDSRYLRSDGRLVWEPEPRACYTLEFKAGKLAFKDCDGHYLAPVGPAGTLKA
  GRNTRPGKDELFDLEESHPQVVLVAANHRYVSVRQGVNVSANQDDELDHETFLMQIDQET
  KKCTFYSSTGGYWTLVTHGGIHATATQVSANTMFEMEWRGRRVALKASNGRYVCMKKNGQ
  LAAISDFVGKDEEFTLKLINRPILVLRGLDGFVCHHRGSNQLDTNRSVYDVFHLSFSDGA
  YRIRGRDGGFWYTGSHGSVCSDGERAEDFVFEFRERGRLAIRARSGKYLRGGASGLLRAD
  ADAPAGTALWEY
• Function: Acts as an actin bundling protein. May play a pivotal role in photoreceptor cell-specific events, such as disk morphogenesis.
• Tissue Specificity: Localized specifically in the outer and inner segments of the photoreceptor cells in the retina.
• Reactome Pathway:
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[1]
Macular degeneration	DISLKKHD	Strong	Genetic Variation	[1]
Retinitis pigmentosa 17	DIS7LCIM	Strong	Genetic Variation	[2]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[3]
Retinitis pigmentosa 30	DISR2JGV	Disputed	Autosomal dominant	[4]

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 Fascin-2 (FSCN2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fascin-2 (FSCN2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fascin-2 (FSCN2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fascin-2 (FSCN2).	[8]

References

• [1] Sequence variations in the retinal fascin FSCN2 gene in a Spanish population with autosomal dominant retinitis pigmentosa or macular degeneration.Mol Vis. 2005 Nov 2;11:922-8.
• [2] Refinement of the RP17 locus for autosomal dominant retinitis pigmentosa, construction of a YAC contig and investigation of the candidate gene retinal fascin.Eur J Hum Genet. 1999 Apr;7(3):332-8. doi: 10.1038/sj.ejhg.5200302.
• [3] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.