Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYSZ9V6)

• DOT Name: Ankyrin repeat and SOCS box protein 10 (ASB10)
• Synonyms: ASB-10
• Gene Name: ASB10
• Related Disease:
  Open-angle glaucoma
  Glaucoma/ocular hypertension
  Obsolete glaucoma 1, open angle, F
  OPTN-related open angle glaucoma
• UniProt ID: ASB10_HUMAN
• Pfam ID: PF00023 ; PF12796 ; PF07525
• Sequence:
  MLMSWSPEECKGQGEPLDDRHPLCARLVEKPSRGSEEHLKSGPGPIVTRTASGPALAFWQ
  AVLAGDVGCVSRILADSSTGLAPDSVFDTSDPERWRDFRFNIRALRLWSLTYEEELTTPL
  HVAASRGHTEVLRLLLRRRARPDSAPGGRTALHEACAAGHTACVHVLLVAGADPNIADQD
  GKRPLHLCRGPGTLECAELLLRFGARVDGRSEEEEETPLHVAARLGHVELADLLLRRGAC
  PDARNAEGWTPLLAACDVRCQSITDAEATTARCLQLCSLLLSAGADADAADQDKQRPLHL
  ACRRGHAAVVELLLSCGVSANTMDYGGHTPLHCALQGPAAALAQSPEHVVRALLNHGAVR
  VWPGALPKVLERWSTCPRTIEVLMNTYSVVQLPEEAVGLVTPETLQKHQRFYSSLFALVR
  QPRSLQHLSRCALRSHLEGSLPQALPRLPLPPRLLRYLQLDFEGVLY
• Function: May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Tissue Specificity: Expressed in the eye. The highest expression is observed in the iris, with moderate levels in the trabecular meshwork (TM), the lamina, and the optic nerve; slightly lower levels in the ciliary body, retina, and choroid; and very low levels in the lens.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[1]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[2]
Obsolete glaucoma 1, open angle, F	DIS6LV3S	Limited	Autosomal dominant	[3]
OPTN-related open angle glaucoma	DISDR98A	Limited	Genetic Variation	[2]

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 Ankyrin repeat and SOCS box protein 10 (ASB10).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Ankyrin repeat and SOCS box protein 10 (ASB10).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ankyrin repeat and SOCS box protein 10 (ASB10).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ankyrin repeat and SOCS box protein 10 (ASB10).	[5]

References

• [1] Variants in ASB10 are associated with open-angle glaucoma. Hum Mol Genet. 2012 Mar 15;21(6):1336-49. doi: 10.1093/hmg/ddr572. Epub 2011 Dec 8.
• [2] Working your SOCS off: The role of ASB10 and protein degradation pathways in glaucoma.Exp Eye Res. 2017 May;158:154-160. doi: 10.1016/j.exer.2016.06.003. Epub 2016 Jun 11.
• [3] 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.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.
• [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.