Details of Drug Off-Target (DOT)

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

• DOT Name: Kelch-like protein 17 (KLHL17)
• Synonyms: Actinfilin
• Gene Name: KLHL17
• Related Disease:
  Infantile epileptic-dyskinetic encephalopathy
  SHOX-related short stature
• UniProt ID: KLH17_HUMAN
• PDB ID: 6HRL
• Pfam ID: PF07707 ; PF00651 ; PF01344
• Sequence:
  MQPRSERPAGRTQSPEHGSPGPGPEAPPPPPPQPPAPEAERTRPRQARPAAPMEGAVQLL
  SREGHSVAHNSKRHYHDAFVAMSRMRQRGLLCDIVLHVAAKEIRAHKVVLASCSPYFHAM
  FTNEMSESRQTHVTLHDIDPQALDQLVQFAYTAEIVVGEGNVQTLLPAASLLQLNGVRDA
  CCKFLLSQLDPSNCLGIRGFADAHSCSDLLKAAHRYVLQHFVDVAKTEEFMLLPLKQVLE
  LVSSDSLNVPSEEEVYRAVLSWVKHDVDARRQHVPRLMKCVRLPLLSRDFLLGHVDAESL
  VRHHPDCKDLLIEALKFHLLPEQRGVLGTSRTRPRRCEGAGPVLFAVGGGSLFAIHGDCE
  AYDTRTDRWHVVASMSTRRARVGVAAVGNRLYAVGGYDGTSDLATVESYDPVTNTWQPEV
  SMGTRRSCLGVAALHGLLYSAGGYDGASCLNSAERYDPLTGTWTSVAAMSTRRRYVRVAT
  LDGNLYAVGGYDSSSHLATVEKYEPQVNVWSPVASMLSRRSSAGVAVLEGALYVAGGNDG
  TSCLNSVERYSPKAGAWESVAPMNIRRSTHDLVAMDGWLYAVGGNDGSSSLNSIEKYNPR
  TNKWVAASCMFTRRSSVGVAVLELLNFPPPSSPTLSVSSTSL
• Function: Substrate-recognition component of some cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes. The BCR(KLHL17) complex mediates the ubiquitination and subsequent degradation of GLUR6. May play a role in the actin-based neuronal function.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	moderate	Genetic Variation	[1]
SHOX-related short stature	DIS4A87B	moderate	Genetic Variation	[1]

2 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 17 (KLHL17).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Kelch-like protein 17 (KLHL17).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Kelch-like protein 17 (KLHL17).	[4]

References

• [1] Copy number variants and infantile spasms: evidence for abnormalities in ventral forebrain development and pathways of synaptic function.Eur J Hum Genet. 2011 Dec;19(12):1238-45. doi: 10.1038/ejhg.2011.121. Epub 2011 Jun 22.
• [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] 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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.