Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6W40XU)

• DOT Name: Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1)
• Synonyms: P5CS; Aldehyde dehydrogenase family 18 member A1
• Gene Name: ALDH18A1
• Related Disease:
  ALDH18A1-related de Barsy syndrome
  Cutis laxa, autosomal dominant 3
  Hereditary spastic paraplegia 9A
  Metabolic disorder
  P5CS deficiency
  Autosomal recessive complex spastic paraplegia type 9B
  Cataract
  Cerebellar ataxia
  Complex hereditary spastic paraplegia
  Connective tissue disorder
  Corpus callosum, agenesis of
  Hepatocellular carcinoma
  Isolated congenital microcephaly
  Lung adenocarcinoma
  Nervous system disease
  Neurocutaneous syndrome
  Ornithine translocase deficiency
  Sturge-Weber syndrome
  Vascular purpura
  Hutchinson-Gilford progeria syndrome
  Melanoma
  Neoplasm
  Retinitis pigmentosa
  Retinopathy
  Autosomal dominant complex spastic paraplegia type 9B
  Autosomal dominant cutis laxa
  Autosomal dominant spastic paraplegia type 9
  Autosomal recessive cutis laxa type 2B
  De Barsy syndrome
  Hereditary spastic paraplegia
• UniProt ID: P5CS_HUMAN
• PDB ID: 2H5G
• EC Number: 1.2.1.41; 2.7.2.11
• Pfam ID: PF00696 ; PF00171
• Sequence:
  MLSQVYRCGFQPFNQHLLPWVKCTTVFRSHCIQPSVIRHVRSWSNIPFITVPLSRTHGKS
  FAHRSELKHAKRIVVKLGSAVVTRGDECGLALGRLASIVEQVSVLQNQGREMMLVTSGAV
  AFGKQRLRHEILLSQSVRQALHSGQNQLKEMAIPVLEARACAAAGQSGLMALYEAMFTQY
  SICAAQILVTNLDFHDEQKRRNLNGTLHELLRMNIVPIVNTNDAVVPPAEPNSDLQGVNV
  ISVKDNDSLAARLAVEMKTDLLIVLSDVEGLFDSPPGSDDAKLIDIFYPGDQQSVTFGTK
  SRVGMGGMEAKVKAALWALQGGTSVVIANGTHPKVSGHVITDIVEGKKVGTFFSEVKPAG
  PTVEQQGEMARSGGRMLATLEPEQRAEIIHHLADLLTDQRDEILLANKKDLEEAEGRLAA
  PLLKRLSLSTSKLNSLAIGLRQIAASSQDSVGRVLRRTRIAKNLELEQVTVPIGVLLVIF
  ESRPDCLPQVAALAIASGNGLLLKGGKEAAHSNRILHLLTQEALSIHGVKEAVQLVNTRE
  EVEDLCRLDKMIDLIIPRGSSQLVRDIQKAAKGIPVMGHSEGICHMYVDSEASVDKVTRL
  VRDSKCEYPAACNALETLLIHRDLLRTPLFDQIIDMLRVEQVKIHAGPKFASYLTFSPSE
  VKSLRTEYGDLELCIEVVDNVQDAIDHIHKYGSSHTDVIVTEDENTAEFFLQHVDSACVF
  WNASTRFSDGYRFGLGAEVGISTSRIHARGPVGLEGLLTTKWLLRGKDHVVSDFSEHGSL
  KYLHENLPIPQRNTN
• Function: Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: Glutamate and glutamine metabolism (R-HSA-8964539)
• BioCyc Pathway: MetaCyc:HS00730-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
ALDH18A1-related de Barsy syndrome	DIST6TR0	Definitive	Autosomal recessive	[1]
Cutis laxa, autosomal dominant 3	DISTXM91	Definitive	Autosomal dominant	[2]
Hereditary spastic paraplegia 9A	DISQHJ22	Definitive	Autosomal dominant	[3]
Metabolic disorder	DIS71G5H	Definitive	Altered Expression	[4]
P5CS deficiency	DISUFH0J	Definitive	Semidominant	[5]
Autosomal recessive complex spastic paraplegia type 9B	DISS571N	Strong	Autosomal dominant	[6]
Cataract	DISUD7SL	Strong	Genetic Variation	[1]
Cerebellar ataxia	DIS9IRAV	Strong	Biomarker	[7]
Complex hereditary spastic paraplegia	DIS9KXQY	Strong	Genetic Variation	[7]
Connective tissue disorder	DISKXBS3	Strong	Biomarker	[6]
Corpus callosum, agenesis of	DISO9P40	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[10]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[11]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[12]
Neurocutaneous syndrome	DISNC82H	Strong	Genetic Variation	[13]
Ornithine translocase deficiency	DISITN7S	Strong	Biomarker	[14]
Sturge-Weber syndrome	DISL0WMD	Strong	Genetic Variation	[13]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[14]
Hutchinson-Gilford progeria syndrome	DISY55BU	moderate	Genetic Variation	[10]
Melanoma	DIS1RRCY	moderate	Biomarker	[15]
Neoplasm	DISZKGEW	moderate	Biomarker	[15]
Retinitis pigmentosa	DISCGPY8	moderate	Biomarker	[10]
Retinopathy	DISB4B0F	moderate	Genetic Variation	[10]
Autosomal dominant complex spastic paraplegia type 9B	DISJ9W2D	Supportive	Autosomal dominant	[13]
Autosomal dominant cutis laxa	DIS2180B	Supportive	Autosomal dominant	[2]
Autosomal dominant spastic paraplegia type 9	DIS3RP1V	Limited	Biomarker	[16]
Autosomal recessive cutis laxa type 2B	DIS7URGV	Limited	Genetic Variation	[17]
De Barsy syndrome	DISUQYF3	Limited	Biomarker	[16]
Hereditary spastic paraplegia	DISGZQV1	Limited	Biomarker	[18]

18 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 Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[24]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[25]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[26]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[27]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[28]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[29]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[26]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[30]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1).	[32]

References

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