Details of Drug Off-Target (DOT)

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

• DOT Name: Kelch-like protein 26 (KLHL26)
• Gene Name: KLHL26
• Related Disease: Gastroesophageal reflux disease
• UniProt ID: KLH26_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF01344 ; PF13964
• Sequence:
  MAESGGSSGGAGGGGAFGAGPGPERPNSTADKNGALKCTFSAPSHSTSLLQGLATLRAQG
  QLLDVVLTINREAFPAHKVVLAACSDYFRAMFTGGMREASQDVIELKGVSARGLRHIIDF
  AYSAEVTLDLDCVQDVLGAAVFLQMLPVVELCEEFLKAAMSVETCLNIGQMATTFSLASL
  RESVDAFTFRHFLQIAEEEDFLRLPLERLVFFLQSNRLQSCAEIDLFRAAVRWLQHDPAR
  RPRASHVLCHIRFPLMQSSELVDSVQTLDIMVEDVLCRQYLLEAFNYQVLPFRQHEMQSP
  RTAVRSDVPSLVTFGGTPYTDSDRSVSSKVYQLPEPGARHFRELTEMEVGCSHTCVAVLD
  NFVYVAGGQHLQYRSGEGAVDACYRYDPHLNRWLRLQAMQESRIQFQLNVLCGMVYATGG
  RNRAGSLASVERYCPRRNEWGYACSLKRRTWGHAGAASGGRLYISGGYGISVEDKKALHC
  YDPVADQWEFKAPMSEPRVLHAMVGAGGRIYALGGRMDHVDRCFDVLAVEYYVPETDQWT
  SVSPMRAGQSEAGCCLLERKIYIVGGYNWRLNNVTGIVQVYNTDTDEWERDLHFPESFAG
  IACAPVLLPRAGTRR
• Function: May play a role in endo(sarco)plasmic reticulum (ER/SR) mitochondrial signaling. May be part of the ubiquitin-proteasome system (UPS) and affect ubiquitination and degradation of target substrates in cardiomyocytes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastroesophageal reflux disease	DISQ8G5S	Strong	Genetic Variation	[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 Kelch-like protein 26 (KLHL26).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kelch-like protein 26 (KLHL26).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Kelch-like protein 26 (KLHL26).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Kelch-like protein 26 (KLHL26).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Kelch-like protein 26 (KLHL26).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Kelch-like protein 26 (KLHL26).	[7]

References

• [1] Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.Nat Commun. 2019 Sep 16;10(1):4219. doi: 10.1038/s41467-019-11968-2.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.