Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5641YJ)

• DOT Name: Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1)
• Gene Name: FANK1
• Related Disease: Fatty liver disease
• UniProt ID: FANK1_HUMAN
• Pfam ID: PF12796
• Sequence:
  MEPQKIMPPSKPHPPVVGKVTHHSIELYWDLEKKAKRQGPQEQWFRFSIEEEDPKMHTYG
  IIYTGYATKHVVEGLEPRTLYRFRLKVTSPSGECEYSPLVSVSTTREPISSEHLHRAVSV
  NDEDLLVRILQGGRVKVDVPNKFGFTALMVAAQKGYTRLVKILVSNGTDVNLKNGSGKDS
  LMLACYAGHLDVVKYLRRHGASWQARDLGGCTALHWAADGGHCSVIEWMIKDGCEVDVVD
  TGSGWTPLMRVSAVSGNQRVASLLIDAGANVNVKDRNGKTPLMVAVLNNHEELVQLLLDK
  GADASVKNEFGKGVLEMARVFDRQSVVSLLEERKKKQRPKKSCVC
• Function: Through the activation of JUN and AP-1-mediated transcription, may regulate apoptosis.
• Tissue Specificity: Mostly restricted to testis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]

1 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 Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Fibronectin type 3 and ankyrin repeat domains protein 1 (FANK1).	[8]

References

• [1] Liver X receptor induces 17-hydroxysteroid dehydrogenase-13 expression through SREBP-1c.Am J Physiol Endocrinol Metab. 2017 Apr 1;312(4):E357-E367. doi: 10.1152/ajpendo.00310.2016. Epub 2017 Mar 7.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] 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.