Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT50NI6Z)

• DOT Name: Aldehyde dehydrogenase family 16 member A1 (ALDH16A1)
• Gene Name: ALDH16A1
• Related Disease:
  Gout
  Mast syndrome
  Hypoxanthine guanine phosphoribosyltransferase partial deficiency
• UniProt ID: A16A1_HUMAN
• Pfam ID: PF00171
• Sequence:
  MAATRAGPRAREIFTSLEYGPVPESHACALAWLDTQDRCLGHYVNGKWLKPEHRNSVPCQ
  DPITGENLASCLQAQAEDVAAAVEAARMAFKGWSAHPGVVRAQHLTRLAEVIQKHQRLLW
  TLESLVTGRAVREVRDGDVQLAQQLLHYHAIQASTQEEALAGWEPMGVIGLILPPTFSFL
  EMMWRICPALAVGCTVVALVPPASPAPLLLAQLAGELGPFPGILNVLSGPASLVPILASQ
  PGIRKVAFCGAPEEGRALRRSLAGECAELGLALGTESLLLLTDTADVDSAVEGVVDAAWS
  DRGPGGLRLLIQESVWDEAMRRLQERMGRLRSGRGLDGAVDMGARGAAACDLVQRFVREA
  QSQGAQVFQAGDVPSERPFYPPTLVSNLPPASPCAQVEVPWPVVVASPFRTAKEALLVAN
  GTPRGGSASVWSERLGQALELGYGLQVGTVWINAHGLRDPSVPTGGCKESGCSWHGGPDG
  LYEYLRPSGTPARLSCLSKNLNYDTFGLAVPSTLPAGPEIGPSPAPPYGLFVGGRFQAPG
  ARSSRPIRDSSGNLHGYVAEGGAKDIRGAVEAAHQAFPGWAGQSPGARAALLWALAAALE
  RRKSTLASRLERQGAELKAAEAEVELSARRLRAWGARVQAQGHTLQVAGLRGPVLRLREP
  LGVLAVVCPDEWPLLAFVSLLAPALAYGNTVVMVPSAACPLLALEVCQDMATVFPAGLAN
  VVTGDRDHLTRCLALHQDVQAMWYFGSAQGSQFVEWASAGNLKPVWASRGCPRAWDQEAE
  GAGPELGLRVARTKALWLPMGD

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Biomarker	[1]
Mast syndrome	DIS78QKW	moderate	Biomarker	[2]
Hypoxanthine guanine phosphoribosyltransferase partial deficiency	DISH99SV	Limited	Biomarker	[3]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Aldehyde dehydrogenase family 16 member A1 (ALDH16A1) affects the abundance of Uric acid.	[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 Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[4]

7 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 Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Aldehyde dehydrogenase family 16 member A1 (ALDH16A1).	[11]

References

• [1] Identification of low-frequency variants associated with gout and serum uric acid levels. Nat Genet. 2011 Oct 9;43(11):1127-30. doi: 10.1038/ng.972.
• [2] Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1.Neurogenetics. 2009 Jul;10(3):217-28. doi: 10.1007/s10048-009-0172-6. Epub 2009 Jan 31.
• [3] ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1. Chem Biol Interact. 2013 Feb 25;202(1-3):22-31.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Identification of low-frequency variants associated with gout and serum uric acid levels. Nat Genet. 2011 Oct 9;43(11):1127-30. doi: 10.1038/ng.972.