Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3JI5GB)

• DOT Name: Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8)
• Synonyms: IBDH; EC 1.3.8.5; Activator-recruited cofactor 42 kDa component; ARC42; Acyl-CoA dehydrogenase family member 8; ACAD-8
• Gene Name: ACAD8
• Related Disease:
  Isobutyryl-CoA dehydrogenase deficiency
  Parkinson disease
  Acute gouty arthritis
  Adenoma
  Arthritis
  Autism
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Cytomegalovirus infection
  Depression
  Diverticulitis
  Enthesopathy
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Immunodeficiency
  Intestinal disorder
  Mental disorder
  Multiple sclerosis
  Obesity
  Primary sclerosing cholangitis
  Psoriatic arthritis
  Tuberculosis
  Type-1 diabetes
  Anemia
  Coeliac disease
  Colitis
  Early-onset posterior polar cataract
  Leukopenia
  Iron-deficiency anemia
  Venous thromboembolism
  Anxiety
  Anxiety disorder
  Asthma
  Central diabetes insipidus
  Colon cancer
  Colon carcinoma
  Irritable bowel syndrome
  Lung cancer
  Lung carcinoma
  Malabsorption syndrome
  Non-insulin dependent diabetes
  Osteoporosis
  Ulcerative colitis
• UniProt ID: ACAD8_HUMAN
• PDB ID: 1RX0
• EC Number: 1.3.8.5
• Pfam ID: PF00441 ; PF02770 ; PF02771
• Sequence:
  MLWSGCRRFGARLGCLPGGLRVLVQTGHRSLTSCIDPSMGLNEEQKEFQKVAFDFAAREM
  APNMAEWDQKELFPVDVMRKAAQLGFGGVYIQTDVGGSGLSRLDTSVIFEALATGCTSTT
  AYISIHNMCAWMIDSFGNEEQRHKFCPPLCTMEKFASYCLTEPGSGSDAASLLTSAKKQG
  DHYILNGSKAFISGAGESDIYVVMCRTGGPGPKGISCIVVEKGTPGLSFGKKEKKVGWNS
  QPTRAVIFEDCAVPVANRIGSEGQGFLIAVRGLNGGRINIASCSLGAAHASVILTRDHLN
  VRKQFGEPLASNQYLQFTLADMATRLVAARLMVRNAAVALQEERKDAVALCSMAKLFATD
  ECFAICNQALQMHGGYGYLKDYAVQQYVRDSRVHQILEGSNEVMRILISRSLLQE
• Function: Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway. To a lesser extent, also able to catalyze the oxidation of (2S)-2-methylbutanoyl-CoA.
• Tissue Specificity: Detected at comparable levels in heart, lung, brain, skeletal muscle, pancreas and placenta. Weakly expressed in liver and kidney.
• KEGG Pathway:
  Valine, leucine and isoleucine degradation (hsa00280)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Branched-chain amino acid catabolism (R-HSA-70895)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isobutyryl-CoA dehydrogenase deficiency	DIS9ORX6	Definitive	Autosomal recessive	[1]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[2]
Acute gouty arthritis	DISY5UJH	Strong	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Biomarker	[4]
Arthritis	DIST1YEL	Strong	Biomarker	[5]
Autism	DISV4V1Z	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[10]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Biomarker	[12]
Diverticulitis	DIS1AK7Q	Strong	Biomarker	[13]
Enthesopathy	DIS2724M	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[14]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[14]
Immunodeficiency	DIS093I0	Strong	Biomarker	[15]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[16]
Mental disorder	DIS3J5R8	Strong	Biomarker	[17]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[13]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Biomarker	[19]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[20]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[21]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[22]
Anemia	DISTVL0C	moderate	Biomarker	[23]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[24]
Colitis	DISAF7DD	moderate	Biomarker	[25]
Early-onset posterior polar cataract	DISJFK9W	moderate	Biomarker	[26]
Leukopenia	DISJMBMM	moderate	Biomarker	[27]
Iron-deficiency anemia	DIS0VQYF	Disputed	Genetic Variation	[23]
Venous thromboembolism	DISUR7CR	Disputed	Biomarker	[13]
Anxiety	DISIJDBA	Limited	Biomarker	[28]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[28]
Asthma	DISW9QNS	Limited	Genetic Variation	[29]
Central diabetes insipidus	DISJ4P9O	Limited	Biomarker	[30]
Colon cancer	DISVC52G	Limited	Biomarker	[31]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[31]
Irritable bowel syndrome	DIS27206	Limited	Altered Expression	[32]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[33]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[33]
Malabsorption syndrome	DISGMUVS	Limited	Biomarker	[34]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[35]
Osteoporosis	DISF2JE0	Limited	Biomarker	[36]
Ulcerative colitis	DIS8K27O	Limited	Biomarker	[37]

6 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 Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[42]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Isobutyryl-CoA dehydrogenase, mitochondrial (ACAD8).	[44]

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