Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3XXNI)

• DOT Name: Acyl-CoA-binding domain-containing protein 6 (ACBD6)
• Gene Name: ACBD6
• Related Disease:
  Short stature-pituitary and cerebellar defects-small sella turcica syndrome
  Intellectual disability
• UniProt ID: ACBD6_HUMAN
• PDB ID: 2COP
• Pfam ID: PF00887 ; PF12796
• Sequence:
  MASSFLPAGAITGDSGGELSSGDDSGEVEFPHSPEIEETSCLAELFEKAAAHLQGLIQVA
  SREQLLYLYARYKQVKVGNCNTPKPSFFDFEGKQKWEAWKALGDSSPSQAMQEYIAVVKK
  LDPGWNPQIPEKKGKEANTGFGGPVISSLYHEETIREEDKNIFDYCRENNIDHITKAIKS
  KNVDVNVKDEEGRALLHWACDRGHKELVTVLLQHRADINCQDNEGQTALHYASACEFLDI
  VELLLQSGADPTLRDQDGCLPEEVTGCKTVSLVLQRHTTGKA
• Function: Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA, lower affinity for unsaturated C20:4-CoA, and very weak affinity for saturated C16:0-CoA. Does not bind fatty acids.
• Tissue Specificity: Detected in placenta and spleen (at protein level). Detected in placenta, umbilical cord blood, CD34-positive hematopoietic progenitor cells and bone marrow.
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Short stature-pituitary and cerebellar defects-small sella turcica syndrome	DIS11311	Strong	CausalMutation	[1]
Intellectual disability	DISMBNXP	Limited	Autosomal recessive	[2]

8 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 Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[9]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Acyl-CoA-binding domain-containing protein 6 (ACBD6).	[10]

References

• [1] Molecular and Clinical Findings in Patients with LHX4 and OTX2 Mutations.Clin Pediatr Endocrinol. 2013 Apr;22(2):15-23. doi: 10.1292/cpe.22.15. Epub 2013 Apr 26.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] 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.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.