Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIZA3AM)

• DOT Name: Kelch domain-containing protein 8A (KLHDC8A)
• Synonyms: Substitute for delta-EGFR expression 1; S-delta-E1
• Gene Name: KLHDC8A
• UniProt ID: KLD8A_HUMAN
• Pfam ID: PF01344 ; PF13964
• Sequence:
  MEVPNVKDFQWKRLAPLPSRRVYCSLLETGGQVYAIGGCDDNGVPMDCFEVYSPEADQWT
  ALPRLPTARAGVAVTALGKRIMVIGGVGTNQLPLKVVEMYNIDEGKWKKRSMLREAAMGI
  SVTAKDYRVYAAGGMGLDLRPHNHLQHYDMLKDMWVSLAPMPTPRYAATSFLRGSKIYVL
  GGRQSKYAVNAFEVFDIETRSWTKFPNIPYKRAFSSFVTLDNHLYSLGGLRQGRLYRQPK
  FLRTMDVFDMEQGGWLKMERSFFLKKRRADFVAGSLSGRVIVAGGLGNQPTVLETAEAFH
  PGKNKWEILPAMPTPRCACSSIVVKNCLLAVGGVNQGLSDAVEALCVSDS

Molecular Interaction Atlas (MIA) of This DOT

9 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 Kelch domain-containing protein 8A (KLHDC8A).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[5]
Permethrin	DMZ0Q1G	Approved	Permethrin affects the expression of Kelch domain-containing protein 8A (KLHDC8A).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Kelch domain-containing protein 8A (KLHDC8A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Kelch domain-containing protein 8A (KLHDC8A).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Kelch domain-containing protein 8A (KLHDC8A).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] 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.