Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFAG3M0)

• DOT Name: Acyl-CoA dehydrogenase family member 10 (ACAD10)
• Synonyms: ACAD-10; EC 1.3.99.-
• Gene Name: ACAD10
• Related Disease:
  Age-related macular degeneration
  Esophageal cancer
  Hyperinsulinemia
  Neoplasm of esophagus
  Neovascular age-related macular degeneration
  Non-insulin dependent diabetes
  Glycogen storage disease type II
  Melanoma
• UniProt ID: ACD10_HUMAN
• EC Number: 1.3.99.-
• Pfam ID: PF00441 ; PF02770 ; PF02771 ; PF01636 ; PF00702
• Sequence:
  MCVRSCFQSPRLQWVWRTAFLKHTQRRHQGSHRWTHLGGSTYRAVIFDMGGVLIPSPGRV
  AAEWEVQNRIPSGTILKALMEGGENGPWMRFMRAEITAEGFLREFGRLCSEMLKTSVPVD
  SFFSLLTSERVAKQFPVMTEAITQIRAKGLQTAVLSNNFYLPNQKSFLPLDRKQFDVIVE
  SCMEGICKPDPRIYKLCLEQLGLQPSESIFLDDLGTNLKEAARLGIHTIKVNDPETAVKE
  LEALLGFTLRVGVPNTRPVKKTMEIPKDSLQKYLKDLLGIQTTGPLELLQFDHGQSNPTY
  YIRLANRDLVLRKKPPGTLLPSAHAIEREFRIMKALANAGVPVPNVLDLCEDSSVIGTPF
  YVMEYCPGLIYKDPSLPGLEPSHRRAIYTAMNTVLCKIHSVDLQAVGLEDYGKQGDYIPR
  QVRTWVKQYRASETSTIPAMERLIEWLPLHLPRQQRTTVVHGDFRLDNLVFHPEEPEVLA
  VLDWELSTLGDPLADVAYSCLAHYLPSSFPVLRGINDCDLTQLGIPAAEEYFRMYCLQMG
  LPPTENWNFYMAFSFFRVAAILQGVYKRSLTGQASSTYAEQTGKLTEFVSNLAWDFAVKE
  GFRVFKEMPFTNPLTRSYHTWARPQSQWCPTGSRSYSSVPEASPAHTSRGGLVISPESLS
  PPVRELYHRLKHFMEQRVYPAEPELQSHQASAARWSPSPLIEDLKEKAKAEGLWNLFLPL
  EADPEKKYGAGLTNVEYAHLCELMGTSLYAPEVCNCSAPDTGNMELLVRYGTEAQKARWL
  IPLLEGKARSCFAMTEPQVASSDATNIEASIREEDSFYVINGHKWWITGILDPRCQLCVF
  MGKTDPHAPRHRQQSVLLVPMDTPGIKIIRPLTVYGLEDAPGGHGEVRFEHVRVPKENMV
  LGPGRGFEIAQGRLGPGRIHHCMRLIGFSERALALMKARVKSRLAFGKPLVEQGTVLADI
  AQSRVEIEQARLLVLRAAHLMDLAGNKAAALDIAMIKMVAPSMASRVIDRAIQAFGAAGL
  SSDYPLAQFFTWARALRFADGPDEVHRATVAKLELKHRI
• Function: Acyl-CoA dehydrogenase only active with R- and S-2-methyl-C15-CoA.
• Tissue Specificity: Widely expressed with highest expression in fetal brain, followed by heart, muscle, kidney and adult brain. Expression levels varying from isoform to isoform.
• Reactome Pathway: Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[1]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[2]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[3]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[2]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Glycogen storage disease type II	DISXZPBC	Limited	Genetic Variation	[1]
Melanoma	DIS1RRCY	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acyl-CoA dehydrogenase family member 10 (ACAD10).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Acyl-CoA dehydrogenase family member 10 (ACAD10).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acyl-CoA dehydrogenase family member 10 (ACAD10).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acyl-CoA dehydrogenase family member 10 (ACAD10).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Acyl-CoA dehydrogenase family member 10 (ACAD10).	[11]

References

• [1] Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial.JAMA Ophthalmol. 2019 Jul 1;137(7):738-744. doi: 10.1001/jamaophthalmol.2019.0868.
• [2] Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations.Nat Genet. 2011 Jun 5;43(7):679-84. doi: 10.1038/ng.849.
• [3] Variants in ACAD10 are associated with type 2 diabetes, insulin resistance and lipid oxidation in Pima Indians.Diabetologia. 2010 Jul;53(7):1349-53. doi: 10.1007/s00125-010-1695-y.
• [4] A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.Nat Genet. 2016 Feb;48(2):134-43. doi: 10.1038/ng.3448. Epub 2015 Dec 21.
• [5] Investigating the link of ACAD10 deficiency to type 2 diabetes mellitus.J Inherit Metab Dis. 2018 Jan;41(1):49-57. doi: 10.1007/s10545-017-0013-y. Epub 2017 Jan 24.
• [6] An Ancient, Unified Mechanism for Metformin Growth Inhibition in C.elegans and Cancer.Cell. 2016 Dec 15;167(7):1705-1718.e13. doi: 10.1016/j.cell.2016.11.055.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.