Details of Drug Off-Target (DOT)

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

• DOT Name: Killer cell lectin-like receptor subfamily G member 2 (KLRG2)
• Synonyms: C-type lectin domain family 15 member B
• Gene Name: KLRG2
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: KLRG2_HUMAN
• Pfam ID: PF00059
• Sequence:
  MEESWEAAPGGQAGAELPMEPVGSLVPTLEQPQVPAKVRQPEGPESSPSPAGAVEKAAGA
  GLEPSSKKKPPSPRPGSPRVPPLSLGYGVCPEPPSPGPALVKLPRNGEAPGAEPAPSAWA
  PMELQVDVRVKPVGAAGGSSTPSPRPSTRFLKVPVPESPAFSRHADPAHQLLLRAPSQGG
  TWGRRSPLAAARTESGCDAEGRASPAEGSAGSPGSPTCCRCKELGLEKEDAALLPRAGLD
  GDEKLPRAVTLTGLPMYVKSLYWALAFMAVLLAVSGVVIVVLASRAGARCQQCPPGWVLS
  EEHCYYFSAEAQAWEASQAFCSAYHATLPLLSHTQDFLGRYPVSRHSWVGAWRGPQGWHW
  IDEAPLPPQLLPEDGEDNLDINCGALEEGTLVAANCSTPRPWVCAKGTQ

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	moderate	Genetic Variation	[1]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[12]

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 increases the methylation of Killer cell lectin-like receptor subfamily G member 2 (KLRG2).	[9]

References

• [1] Fine-mapping of prostate cancer aggressiveness loci on chromosome 7q22-35.Prostate. 2011 May 15;71(7):682-9. doi: 10.1002/pros.21284. Epub 2010 Oct 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] 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.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [9] 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.
• [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.
• [11] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.