Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5B6R9Y)

• DOT Name: Glycine--tRNA ligase (GARS1)
• Synonyms: EC 6.1.1.14; Diadenosine tetraphosphate synthetase; Ap4A synthetase; EC 2.7.7.-; Glycyl-tRNA synthetase; GlyRS; Glycyl-tRNA synthetase 1
• Gene Name: GARS1
• Related Disease:
  Charcot-Marie-Tooth disease type 2D
  Myocardial infarction
  Neoplasm
  Neuronopathy, distal hereditary motor, type 5A
  Rheumatoid arthritis
  Calciphylaxis
  Charcot-Marie-Tooth disease type 2
  Dermatomyositis
  Estrogen-receptor positive breast cancer
  Hereditary motor and sensory neuropathy
  Juvenile amyotrophic lateral sclerosis
  Mitochondrial disease
  Myositis disease
  Neurodegenerative disease
  Plasma cell myeloma
  Amyotrophic lateral sclerosis
  Hyperekplexia
  Spinal muscular atrophy
  Spinal muscular atrophy, infantile, James type
  Charcot-Marie-Tooth disease type 3
  Congenital generalized lipodystrophy
  Corpus callosum, agenesis of
  Distal hereditary motor neuropathy
  Hepatocellular carcinoma
  Hereditary spastic paraplegia 17
  Intellectual disability
  Neuronopathy, distal hereditary motor, type 5
  Peripheral neuropathy
  Peripheral sensory neuropathies
  Silver-Russell syndrome
• UniProt ID: GARS_HUMAN
• PDB ID: 2PME; 2PMF; 2Q5H; 2Q5I; 2ZT5; 2ZT6; 2ZT7; 2ZT8; 2ZXF; 4KQE; 4KR2; 4KR3; 4QEI; 5E6M
• EC Number: 2.7.7.-; 6.1.1.14
• Pfam ID: PF03129 ; PF00587 ; PF00458
• Sequence:
  MPSPRPVLLRGARAALLLLLPPRLLARPSLLLRRSLSAASCPPISLPAAASRSSMDGAGA
  EEVLAPLRLAVRQQGDLVRKLKEDKAPQVDVDKAVAELKARKRVLEAKELALQPKDDIVD
  RAKMEDTLKRRFFYDQAFAIYGGVSGLYDFGPVGCALKNNIIQTWRQHFIQEEQILEIDC
  TMLTPEPVLKTSGHVDKFADFMVKDVKNGECFRADHLLKAHLQKLMSDKKCSVEKKSEME
  SVLAQLDNYGQQELADLFVNYNVKSPITGNDLSPPVSFNLMFKTFIGPGGNMPGYLRPET
  AQGIFLNFKRLLEFNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHFVDPSEK
  DHPKFQNVADLHLYLYSAKAQVSGQSARKMRLGDAVEQGVINNTVLGYFIGRIYLYLTKV
  GISPDKLRFRQHMENEMAHYACDCWDAESKTSYGWIEIVGCADRSCYDLSCHARATKVPL
  VAEKPLKEPKTVNVVQFEPSKGAIGKAYKKDAKLVMEYLAICDECYITEMEMLLNEKGEF
  TIETEGKTFQLTKDMINVKRFQKTLYVEEVVPNVIEPSFGLGRIMYTVFEHTFHVREGDE
  QRTFFSFPAVVAPFKCSVLPLSQNQEFMPFVKELSEALTRHGVSHKVDDSSGSIGRRYAR
  TDEIGVAFGVTIDFDTVNKTPHTATLRDRDSMRQIRAEISELPSIVQDLANGNITWADVE
  ARYPLFEGQETGKKETIEE
• Function: Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis.
• Tissue Specificity: Widely expressed, including in brain and spinal cord.; [Isoform 2]: Expressed in brain, spinal cord, muscle, heart and spleen.; [Isoform 1]: Expressed in brain, spinal cord, muscle, heart, spleen and liver.
• KEGG Pathway: Aminoacyl-tR. biosynthesis (hsa00970)
• Reactome Pathway:
  Mitochondrial tRNA aminoacylation (R-HSA-379726)
  Cytosolic tRNA aminoacylation (R-HSA-379716)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Charcot-Marie-Tooth disease type 2D	DISC7AJY	Definitive	Autosomal dominant	[1]
Myocardial infarction	DIS655KI	Definitive	Biomarker	[2]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[3]
Neuronopathy, distal hereditary motor, type 5A	DISD3JAD	Definitive	Autosomal dominant	[4]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[5]
Calciphylaxis	DIS2Y594	Strong	Biomarker	[6]
Charcot-Marie-Tooth disease type 2	DISR30O9	Strong	Genetic Variation	[7]
Dermatomyositis	DIS50C5O	Strong	Biomarker	[8]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Posttranslational Modification	[9]
Hereditary motor and sensory neuropathy	DISR0X2K	Strong	Biomarker	[10]
Juvenile amyotrophic lateral sclerosis	DISKDZC9	Strong	Biomarker	[11]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[12]
Myositis disease	DISCIXF0	Strong	Altered Expression	[8]
Neurodegenerative disease	DISM20FF	Strong	Genetic Variation	[13]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[14]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[15]
Hyperekplexia	DISY3CG8	moderate	Biomarker	[16]
Spinal muscular atrophy	DISTLKOB	moderate	Biomarker	[17]
Spinal muscular atrophy, infantile, James type	DISGL03T	Moderate	Autosomal dominant	[18]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Limited	Biomarker	[10]
Congenital generalized lipodystrophy	DIS4XF8N	Limited	Genetic Variation	[19]
Corpus callosum, agenesis of	DISO9P40	Limited	Genetic Variation	[20]
Distal hereditary motor neuropathy	DISGS2ID	Limited	Genetic Variation	[12]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[21]
Hereditary spastic paraplegia 17	DISI7Y7F	Limited	Biomarker	[19]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[20]
Neuronopathy, distal hereditary motor, type 5	DISTSHF6	Limited	Genetic Variation	[22]
Peripheral neuropathy	DIS7KN5G	Limited	Genetic Variation	[23]
Peripheral sensory neuropathies	DISYWI6M	Limited	Genetic Variation	[24]
Silver-Russell syndrome	DISSVJ1D	Limited	Biomarker	[19]

32 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 Glycine--tRNA ligase (GARS1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glycine--tRNA ligase (GARS1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glycine--tRNA ligase (GARS1).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glycine--tRNA ligase (GARS1).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glycine--tRNA ligase (GARS1).	[29]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glycine--tRNA ligase (GARS1).	[30]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glycine--tRNA ligase (GARS1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycine--tRNA ligase (GARS1).	[31]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glycine--tRNA ligase (GARS1).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycine--tRNA ligase (GARS1).	[33]
Marinol	DM70IK5	Approved	Marinol affects the expression of Glycine--tRNA ligase (GARS1).	[34]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Glycine--tRNA ligase (GARS1).	[35]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Glycine--tRNA ligase (GARS1).	[36]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Glycine--tRNA ligase (GARS1).	[33]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Glycine--tRNA ligase (GARS1).	[30]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Glycine--tRNA ligase (GARS1).	[30]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Glycine--tRNA ligase (GARS1).	[30]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Glycine--tRNA ligase (GARS1).	[30]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Glycine--tRNA ligase (GARS1).	[37]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Glycine--tRNA ligase (GARS1).	[38]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Glycine--tRNA ligase (GARS1).	[39]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Glycine--tRNA ligase (GARS1).	[40]
Epanova	DMHEAGL	Approved	Epanova decreases the expression of Glycine--tRNA ligase (GARS1).	[41]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glycine--tRNA ligase (GARS1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycine--tRNA ligase (GARS1).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Glycine--tRNA ligase (GARS1).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glycine--tRNA ligase (GARS1).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Glycine--tRNA ligase (GARS1).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glycine--tRNA ligase (GARS1).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Glycine--tRNA ligase (GARS1).	[48]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Glycine--tRNA ligase (GARS1).	[49]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Glycine--tRNA ligase (GARS1).	[50]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Glycine--tRNA ligase (GARS1).	[43]

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