Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXAGR7J)

• DOT Name: 4-aminobutyrate aminotransferase, mitochondrial (ABAT)
• Synonyms: EC 2.6.1.19; (S)-3-amino-2-methylpropionate transaminase; EC 2.6.1.22; GABA aminotransferase; GABA-AT; Gamma-amino-N-butyrate transaminase; GABA transaminase; GABA-T; L-AIBAT
• Gene Name: ABAT
• Related Disease:
  GABA aminotransaminase deficiency
  Infantile spasm
• UniProt ID: GABT_HUMAN
• EC Number: 2.6.1.19; 2.6.1.22
• Pfam ID: PF00202
• Sequence:
  MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
  QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ
  NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR
  SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS
  FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG
  DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM
  TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL
  DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF
  RDHHAHLFLNIFSDILADFK
• Function: Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
• Tissue Specificity: Liver > pancreas > brain > kidney > heart > placenta.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Valine, leucine and isoleucine degradation (hsa00280)
  beta-Alanine metabolism (hsa00410)
  Propanoate metabolism (hsa00640)
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
  GABAergic sy.pse (hsa04727)
• Reactome Pathway: Degradation of GABA (R-HSA-916853)
• BioCyc Pathway: MetaCyc:HS02477-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
GABA aminotransaminase deficiency	DISB4GJ1	Strong	Autosomal recessive	[1]
Infantile spasm	DISZSKDG	Moderate	Autosomal recessive	[2]

3 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 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[20]
Glyphosate	DM0AFY7	Investigative	Glyphosate affects the methylation of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[16]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[26]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[27]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of 4-aminobutyrate aminotransferase, mitochondrial (ABAT).	[29]

References

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• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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• [28] Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women. Environ Health Perspect. 2022 Apr;130(4):47001. doi: 10.1289/EHP10174. Epub 2022 Apr 4.
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