Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVVDNW0)

• DOT Name: Glycine dehydrogenase (GLDC)
• Synonyms: decarboxylating), mitochondrial (EC 1.4.4.2; Glycine cleavage system P protein; Glycine decarboxylase; Glycine dehydrogenase (aminomethyl-transferring)
• Gene Name: GLDC
• Related Disease:
  Glycine encephalopathy
  Atypical glycine encephalopathy
  Infantile glycine encephalopathy
  Neonatal glycine encephalopathy
• UniProt ID: GCSP_HUMAN
• PDB ID: 6I33; 6I34; 6I35
• EC Number: 1.4.4.2
• Pfam ID: PF01212 ; PF21478 ; PF02347
• Sequence:
  MQSCARAWGLRLGRGVGGGRRLAGGSGPCWAPRSRDSSSGGGDSAAAGASRLLERLLPRH
  DDFARRHIGPGDKDQREMLQTLGLASIDELIEKTVPANIRLKRPLKMEDPVCENEILATL
  HAISSKNQIWRSYIGMGYYNCSVPQTILRNLLENSGWITQYTPYQPEVSQGRLESLLNYQ
  TMVCDITGLDMANASLLDEGTAAAEALQLCYRHNKRRKFLVDPRCHPQTIAVVQTRAKYT
  GVLTELKLPCEMDFSGKDVSGVLFQYPDTEGKVEDFTELVERAHQSGSLACCATDLLALC
  ILRPPGEFGVDIALGSSQRFGVPLGYGGPHAAFFAVRESLVRMMPGRMVGVTRDATGKEV
  YRLALQTREQHIRRDKATSNICTAQALLANMAAMFAIYHGSHGLEHIARRVHNATLILSE
  GLKRAGHQLQHDLFFDTLKIQCGCSVKEVLGRAAQRQINFRLFEDGTLGISLDETVNEKD
  LDDLLWIFGCESSAELVAESMGEECRGIPGSVFKRTSPFLTHQVFNSYHSETNIVRYMKK
  LENKDISLVHSMIPLGSCTMKLNSSSELAPITWKEFANIHPFVPLDQAQGYQQLFRELEK
  DLCELTGYDQVCFQPNSGAQGEYAGLATIRAYLNQKGEGHRTVCLIPKSAHGTNPASAHM
  AGMKIQPVEVDKYGNIDAVHLKAMVDKHKENLAAIMITYPSTNGVFEENISDVCDLIHQH
  GGQVYLDGANMNAQVGICRPGDFGSDVSHLNLHKTFCIPHGGGGPGMGPIGVKKHLAPFL
  PNHPVISLKRNEDACPVGTVSAAPWGSSSILPISWAYIKMMGGKGLKQATETAILNANYM
  AKRLETHYRILFRGARGYVGHEFILDTRPFKKSANIEAVDVAKRLQDYGFHAPTMSWPVA
  GTLMVEPTESEDKAELDRFCDAMISIRQEIADIEEGRIDPRVNPLKMSPHSLTCVTSSHW
  DRPYSREVAAFPLPFVKPENKFWPTIARIDDIYGDQHLVCTCPPMEVYESPFSEQKRASS
• Function: The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH).
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  Lipoic acid metabolism (hsa00785)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway: Glycine degradation (R-HSA-6783984)
• BioCyc Pathway: MetaCyc:HS00622-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycine encephalopathy	DISI2XE5	Definitive	Autosomal recessive	[1]
Atypical glycine encephalopathy	DIS9KV6Z	Supportive	Unknown	[2]
Infantile glycine encephalopathy	DISLOECI	Supportive	Autosomal recessive	[2]
Neonatal glycine encephalopathy	DIS7A6BM	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Glycine dehydrogenase (GLDC).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Glycine dehydrogenase (GLDC).	[24]

26 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 Glycine dehydrogenase (GLDC).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glycine dehydrogenase (GLDC).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycine dehydrogenase (GLDC).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycine dehydrogenase (GLDC).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glycine dehydrogenase (GLDC).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glycine dehydrogenase (GLDC).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycine dehydrogenase (GLDC).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glycine dehydrogenase (GLDC).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glycine dehydrogenase (GLDC).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glycine dehydrogenase (GLDC).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycine dehydrogenase (GLDC).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Glycine dehydrogenase (GLDC).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Glycine dehydrogenase (GLDC).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glycine dehydrogenase (GLDC).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Glycine dehydrogenase (GLDC).	[17]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Glycine dehydrogenase (GLDC).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Glycine dehydrogenase (GLDC).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Glycine dehydrogenase (GLDC).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycine dehydrogenase (GLDC).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glycine dehydrogenase (GLDC).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycine dehydrogenase (GLDC).	[21]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Glycine dehydrogenase (GLDC).	[22]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Glycine dehydrogenase (GLDC).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glycine dehydrogenase (GLDC).	[25]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Glycine dehydrogenase (GLDC).	[26]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of Glycine dehydrogenase (GLDC).	[22]

References

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