Details of Drug Off-Target (DOT)

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

• DOT Name: High mobility group protein 20A (HMG20A)
• Synonyms: HMG box-containing protein 20A; HMG domain-containing protein 1; HMG domain-containing protein HMGX1
• Gene Name: HMG20A
• Related Disease:
  Crohn disease
  Obesity
  Non-insulin dependent diabetes
• UniProt ID: HM20A_HUMAN
• Pfam ID: PF00505
• Sequence:
  MENLMTSSTLPPLFADEDGSKESNDLATTGLNHPEVPYSSGATSSTNNPEFVEDLSQGQL
  LQSESSNAAEGNEQRHEDEQRSKRGGWSKGRKRKKPLRDSNAPKSPLTGYVRFMNERREQ
  LRAKRPEVPFPEITRMLGNEWSKLPPEEKQRYLDEADRDKERYMKELEQYQKTEAYKVFS
  RKTQDRQKGKSHRQDAARQATHDHEKETEVKERSVFDIPIFTEEFLNHSKAREAELRQLR
  KSNMEFEERNAALQKHVESMRTAVEKLEVDVIQERSRNTVLQQHLETLRQVLTSSFASMP
  LPGSGETPTVDTIDSYMNRLHSIILANPQDNENFIATVREVVNRLDR
• Function: Plays a role in neuronal differentiation as chromatin-associated protein. Acts as inhibitor of HMG20B. Overcomes the repressive effects of the neuronal silencer REST and induces the activation of neuronal-specific genes. Involved in the recruitment of the histone methyltransferase KMT2A/MLL1 and consequent increased methylation of histone H3 lysine 4.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[3]

6 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 High mobility group protein 20A (HMG20A).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of High mobility group protein 20A (HMG20A).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of High mobility group protein 20A (HMG20A).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of High mobility group protein 20A (HMG20A).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of High mobility group protein 20A (HMG20A).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of High mobility group protein 20A (HMG20A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of High mobility group protein 20A (HMG20A).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of High mobility group protein 20A (HMG20A).	[10]

References

• [1] Haplotype synthesis analysis reveals functional variants underlying known genome-wide associated susceptibility loci.Bioinformatics. 2016 Jul 15;32(14):2136-42. doi: 10.1093/bioinformatics/btw125. Epub 2016 Mar 21.
• [2] Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects.Eur J Hum Genet. 2016 Jun;24(6):903-10. doi: 10.1038/ejhg.2015.212. Epub 2015 Sep 23.
• [3] The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.Cell Death Dis. 2018 Feb 15;9(3):279. doi: 10.1038/s41419-018-0272-z.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] 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.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.