Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRXHR2P)

• DOT Name: Solute carrier family 35 member F1 (SLC35F1)
• Gene Name: SLC35F1
• Related Disease:
  Adult glioblastoma
  Atrial fibrillation
  Epilepsy
  Glioblastoma multiforme
  Familial atrial fibrillation
• UniProt ID: S35F1_HUMAN
• Pfam ID: PF06027
• Sequence:
  MIPPEQPQQQLQPPSPAPPNHVVTTIENLPAEGSGGGGSLSASSRAGVRQRIRKVLNREM
  LISVALGQVLSLLICGIGLTSKYLSEDFHANTPVFQSFLNYILLFLVYTTTLAVRQGEEN
  LLAILRRRWWKYMILGLIDLEANYLVVKAYQYTTLTSIQLLDCFVIPVVILLSWFFLLIR
  YKAVHFIGIVVCILGMGCMVGADVLVGRHQGAGENKLVGDLLVLGGATLYGISNVWEEYI
  IRTLSRVEFLGMIGLFGAFFSGIQLAIMEHKELLKVPWDWQIGLLYVGFSACMFGLYSFM
  PVVIKKTSATSVNLSLLTADLYSLFCGLFLFHYKFSGLYLLSFFTILIGLVLYSSTSTYI
  AQDPRVYKQFRNPSGPVVDLPTTAQVEPSVTYTSLGQETEEEPHVRVA
• Function: Putative solute transporter.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[2]
Epilepsy	DISBB28L	Strong	Genetic Variation	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Solute carrier family 35 member F1 (SLC35F1) increases the Metabolic disorder ADR of Chlorothiazide.	[15]

3 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 Solute carrier family 35 member F1 (SLC35F1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Solute carrier family 35 member F1 (SLC35F1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Solute carrier family 35 member F1 (SLC35F1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 35 member F1 (SLC35F1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 35 member F1 (SLC35F1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[9]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[12]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Solute carrier family 35 member F1 (SLC35F1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 35 member F1 (SLC35F1).	[13]

References

• [1] Expression of Slc35f1 in the murine brain.Cell Tissue Res. 2019 Aug;377(2):167-176. doi: 10.1007/s00441-019-03008-8. Epub 2019 Mar 13.
• [2] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [3] 6q22.1 microdeletion and susceptibility to pediatric epilepsy.Eur J Hum Genet. 2015 Feb;23(2):173-9. doi: 10.1038/ejhg.2014.75. Epub 2014 May 14.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [10] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] 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.
• [14] 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.
• [15] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.