Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFKQ6HO)

• DOT Name: Protein SIX6OS1 (C14ORF39)
• Synonyms: Six6 opposite strand transcript 1
• Gene Name: C14ORF39
• Related Disease:
  Glaucoma/ocular hypertension
  Open-angle glaucoma
  Refractive error
  Premature ovarian failure 18
  Spermatogenic failure 52
• UniProt ID: S6OS1_HUMAN
• Pfam ID: PF15676
• Sequence:
  MNDSLFVSLDRLLLEFVFQYEQDISTKEEMIQRINKCCEDIKENKVTICRIHETINATDE
  EIDHYCKHSEEIKDNCRNWKPTCDVFRKHEDYMQDQFTVYQGTVEKDKEMYHDYICQYKE
  VLKQYQLKYSETPFSREYYEKKREHEEIQSRVLACTEQLKMNETIFMKFRVPAPFPSLTK
  WTLNIVNLRCETQDILKHASNLTKSSSELKKEVDEMEIEINYLNQQISRHNETKALSETL
  EEKNKNTENRKELKERIFGKDEHVLTLNKTQSSQLFLPYESQKLVRPIKMHSSEPRVADI
  KEESSAKQSKLANIDFRQKENDTQIFNDSAVDNHSKCSHITTITSSQKFMQVRLLTPQKQ
  SNSNQWSEKGDKDAEYGDKGTVRQVRESKCTSQAIYTEHFGKSVENDSDEVEERAENFPR
  TSEIPIFLGTPKAVKAPESLEKIKFPKTPPFEINRNRNAVPEVQTEKESPGLSFLMSYTS
  RSPGLNLFDSSVFDTEISSDQFNEHYSARNLNPLSSEQEIGNLLEKPEGEDGFTFSFPSD
  TSTHTFGAGKDDFSFPFSFGQGQNSIPSSSLKGFSSSSQNTTQFTFF
• Function: Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination. Required for the appropriate processing of intermediate recombination nodules before crossover formation.
• Tissue Specificity: Highest expression in retina, skeletal muscle, testis and colon.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[1]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[2]
Refractive error	DISWNEQ1	Strong	Genetic Variation	[3]
Premature ovarian failure 18	DISJZ6ZH	Limited	Unknown	[4]
Spermatogenic failure 52	DISBQ58P	Limited	Unknown	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein SIX6OS1 (C14ORF39).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein SIX6OS1 (C14ORF39).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein SIX6OS1 (C14ORF39).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein SIX6OS1 (C14ORF39).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Protein SIX6OS1 (C14ORF39).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein SIX6OS1 (C14ORF39).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein SIX6OS1 (C14ORF39).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein SIX6OS1 (C14ORF39).	[8]

References

• [1] Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma.Nat Genet. 2018 Aug;50(8):1067-1071. doi: 10.1038/s41588-018-0176-y. Epub 2018 Jul 27.
• [2] Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.Nat Genet. 2016 Feb;48(2):189-94. doi: 10.1038/ng.3482. Epub 2016 Jan 11.
• [3] Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.Nat Genet. 2013 Mar;45(3):314-8. doi: 10.1038/ng.2554. Epub 2013 Feb 10.
• [4] Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans. Am J Hum Genet. 2021 Feb 4;108(2):324-336. doi: 10.1016/j.ajhg.2021.01.010. Epub 2021 Jan 27.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] 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.
• [8] 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.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] 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.