Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0SJSJM)

DOT Name	Lambda-crystallin homolog (CRYL1)
Synonyms	EC 1.1.1.45; L-gulonate 3-dehydrogenase; Gul3DH
Gene Name	CRYL1
Related Disease	Central diabetes insipidus ( ) Hyperinsulinemic hypoglycemia ( ) Neoplasm ( ) Primary hyperoxaluria ( ) Acquired thrombocytopenia ( ) Acute leukaemia ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Alzheimer disease ( ) Autoimmune disease ( ) Beta thalassemia ( ) Beta-thalassemia major ( ) Breast cancer ( ) Breast carcinoma ( ) Cataract ( ) Giardiasis ( ) Hepatocellular carcinoma ( ) Hyperinsulinemia ( ) Hypoglycemia ( ) Intrahepatic cholangiocarcinoma ( ) Mood disorder ( ) Prostate cancer ( ) Prostate neoplasm ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Fetal growth restriction ( ) Liver cancer ( )
UniProt ID	CRYL1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3F3S
EC Number	1.1.1.45
Pfam ID	PF00725 ; PF02737
Sequence	MASSAAGCVVIVGSGVIGRSWAMLFASGGFQVKLYDIEQQQIRNALENIRKEMKLLEQAG SLKGSLSVEEQLSLISGCPNIQEAVEGAMHIQECVPEDLELKKKIFAQLDSIIDDRVILS SSTSCLMPSKLFAGLVHVKQCIVAHPVNPPYYIPLVELVPHPETAPTTVDRTHALMKKIG QCPMRVQKEVAGFVLNRLQYAIISEAWRLVEEGIVSPSDLDLVMSEGLGMRYAFIGPLET MHLNAEGMLSYCDRYSEGIKHVLQTFGPIPEFSRATAEKVNQDMCMKVPDDPEHLAARRQ WRDECLMRLAKLKSQVQPQ
Function	Has high L-gulonate 3-dehydrogenase activity. It also exhibits low dehydrogenase activity toward L-3-hydroxybutyrate (HBA) and L-threonate.
Tissue Specificity	Widely expressed, with highest levels in liver and kidney.
KEGG Pathway	Pentose and glucuro.te interconversions (hsa00040 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Formation of xylulose-5-phosphate (R-HSA-5661270 )

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Central diabetes insipidus	DISJ4P9O	Definitive	Biomarker	[1]
Hyperinsulinemic hypoglycemia	DIS3KP5D	Definitive	Biomarker	[2]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Primary hyperoxaluria	DIS0L16N	Definitive	Biomarker	[4]
Acquired thrombocytopenia	DISXH01C	Strong	Genetic Variation	[5]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Autoimmune disease	DISORMTM	Strong	Biomarker	[8]
Beta thalassemia	DIS5RCQK	Strong	Altered Expression	[9]
Beta-thalassemia major	DISW06BV	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cataract	DISUD7SL	Strong	Genetic Variation	[11]
Giardiasis	DISWUNWK	Strong	Genetic Variation	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[14]
Hypoglycemia	DISRCKR7	Strong	Genetic Variation	[14]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[15]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Altered Expression	[18]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[19]
Liver cancer	DISDE4BI	moderate	Altered Expression	[18]
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⏷ Show the Full List of 26 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 Lambda-crystallin homolog (CRYL1).	[20]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lambda-crystallin homolog (CRYL1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Lambda-crystallin homolog (CRYL1).	[34]
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15 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 Lambda-crystallin homolog (CRYL1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lambda-crystallin homolog (CRYL1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lambda-crystallin homolog (CRYL1).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lambda-crystallin homolog (CRYL1).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lambda-crystallin homolog (CRYL1).	[25]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lambda-crystallin homolog (CRYL1).	[27]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Lambda-crystallin homolog (CRYL1).	[28]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Lambda-crystallin homolog (CRYL1).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Lambda-crystallin homolog (CRYL1).	[28]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Lambda-crystallin homolog (CRYL1).	[30]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lambda-crystallin homolog (CRYL1).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lambda-crystallin homolog (CRYL1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lambda-crystallin homolog (CRYL1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lambda-crystallin homolog (CRYL1).	[33]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Lambda-crystallin homolog (CRYL1).	[35]
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⏷ Show the Full List of 15 Drug(s)

References

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18	Human CRYL1, a novel enzyme-crystallin overexpressed in liver and kidney and downregulated in 58% of liver cancer tissues from 60 Chinese patients, and four new homologs from other mammalians.Gene. 2003 Jan 2;302(1-2):103-13. doi: 10.1016/s0378-1119(02)01095-8.
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22	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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30	Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
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