Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG7O271)

• DOT Name: Pyruvate dehydrogenase protein X component, mitochondrial (PDHX)
• Synonyms: Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex; E3-binding protein; E3BP; Lipoyl-containing pyruvate dehydrogenase complex component X; proX
• Gene Name: PDHX
• Related Disease:
  Leigh syndrome
  Maturity-onset diabetes of the young type 4
  Non-insulin dependent diabetes
  Patent ductus arteriosus
  Pyruvate dehydrogenase E3-binding protein deficiency
  Type-1 diabetes
  Anal intraepithelial neoplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Endocrine pancreas disorder
  Familial hyperinsulinism
  Hyperglycemia
  Hyperinsulinemia
  Intellectual disability
  Kidney cancer
  Maturity-onset diabetes of the young
  Metabolic disorder
  Pancreatic adenocarcinoma
  Pancreatic tumour
  Polycystic kidney disease 1
  Pyruvate dehydrogenase complex deficiency
  Severe combined immunodeficiency
  Systemic lupus erythematosus
  B-cell neoplasm
  Chronic pancreatitis
  Fetal growth restriction
  Neonatal diabetes mellitus
  Type-1/2 diabetes
  Colorectal adenocarcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Dystonia
  Epithelial ovarian cancer
  Insulinoma
  Matthew-Wood syndrome
  Pancreatic ductal carcinoma
• UniProt ID: ODPX_HUMAN
• PDB ID: 1ZY8; 2DNC; 2F5Z; 2F60; 6H60
• Pfam ID: PF00198 ; PF00364 ; PF02817
• Sequence:
  MAASWRLGCDPRLLRYLVGFPGRRSVGLVKGALGWSVSRGANWRWFHSTQWLRGDPIKIL
  MPSLSPTMEEGNIVKWLKKEGEAVSAGDALCEIETDKAVVTLDASDDGILAKIVVEEGSK
  NIRLGSLIGLIVEEGEDWKHVEIPKDVGPPPPVSKPSEPRPSPEPQISIPVKKEHIPGTL
  RFRLSPAARNILEKHSLDASQGTATGPRGIFTKEDALKLVQLKQTGKITESRPTPAPTAT
  PTAPSPLQATAGPSYPRPVIPPVSTPGQPNAVGTFTEIPASNIRRVIAKRLTESKSTVPH
  AYATADCDLGAVLKVRQDLVKDDIKVSVNDFIIKAAAVTLKQMPDVNVSWDGEGPKQLPF
  IDISVAVATDKGLLTPIIKDAAAKGIQEIADSVKALSKKARDGKLLPEEYQGGSFSISNL
  GMFGIDEFTAVINPPQACILAVGRFRPVLKLTEDEEGNAKLQQRQLITVTMSSDSRVVDD
  ELATRFLKSFKANLENPIRLA
• Function: Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
• KEGG Pathway: Metabolic pathways (hsa01100)
• Reactome Pathway:
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
  Signaling by Retinoic Acid (R-HSA-5362517)
  Pyruvate metabolism (R-HSA-70268)
  Regulation of pyruvate dehydrogenase (PDH) complex (R-HSA-204174)
• BioCyc Pathway: MetaCyc:ENSG00000110435-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[1]
Maturity-onset diabetes of the young type 4	DISN46VD	Definitive	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[3]
Patent ductus arteriosus	DIS9P8YS	Definitive	Biomarker	[4]
Pyruvate dehydrogenase E3-binding protein deficiency	DISXRU5D	Definitive	Autosomal recessive	[5]
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[6]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Endocrine pancreas disorder	DIS3VD5T	Strong	Biomarker	[4]
Familial hyperinsulinism	DISHQKQE	Strong	Altered Expression	[9]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[10]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Biomarker	[12]
Kidney cancer	DISBIPKM	Strong	Altered Expression	[13]
Maturity-onset diabetes of the young	DISG75M5	Strong	Biomarker	[14]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[15]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[16]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[17]
Polycystic kidney disease 1	DIS9FB3R	Strong	Biomarker	[18]
Pyruvate dehydrogenase complex deficiency	DIS8RZP9	Strong	Genetic Variation	[19]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[20]
B-cell neoplasm	DISVY326	moderate	Biomarker	[21]
Chronic pancreatitis	DISBUOMJ	moderate	Biomarker	[22]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[23]
Neonatal diabetes mellitus	DISFHF9K	moderate	Genetic Variation	[24]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[25]
Colorectal adenocarcinoma	DISPQOUB	Limited	Altered Expression	[26]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[26]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[26]
Dystonia	DISJLFGW	Limited	Biomarker	[27]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[28]
Insulinoma	DISIU1JS	Limited	Altered Expression	[29]
Matthew-Wood syndrome	DISA7HR7	Limited	Genetic Variation	[30]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Genetic Variation	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[37]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[38]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[41]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Pyruvate dehydrogenase protein X component, mitochondrial (PDHX).	[42]

References

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