Details of Drug Off-Target (DOT)

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

• DOT Name: Neutral alpha-glucosidase C (GANC)
• Synonyms: EC 3.2.1.20
• Gene Name: GANC
• Related Disease:
  Congenital dyserythropoietic anemia
  Panic disorder
• UniProt ID: GANC_HUMAN
• EC Number: 3.2.1.20
• Pfam ID: PF13802 ; PF01055 ; PF21365
• Sequence:
  MEAAVKEEISLEDEAVDKNIFRDCNKIAFYRRQKQWLSKKSTYQALLDSVTTDEDSTRFQ
  IINEASKVPLLAEIYGIEGNIFRLKINEETPLKPRFEVPDVLTSKPSTVRLISCSGDTGS
  LILADGKGDLKCHITANPFKVDLVSEEEVVISINSLGQLYFEHLQILHKQRAAKENEEET
  SVDTSQENQEDLGLWEEKFGKFVDIKANGPSSIGLDFSLHGFEHLYGIPQHAESHQLKNT
  GDGDAYRLYNLDVYGYQIYDKMGIYGSVPYLLAHKLGRTIGIFWLNASETLVEINTEPAV
  EYTLTQMGPVAAKQKVRSRTHVHWMSESGIIDVFLLTGPTPSDVFKQYSHLTGTQAMPPL
  FSLGYHQCRWNYEDEQDVKAVDAGFDEHDIPYDAMWLDIEHTEGKRYFTWDKNRFPNPKR
  MQELLRSKKRKLVVISDPHIKIDPDYSVYVKAKDQGFFVKNQEGEDFEGVCWPGLSSYLD
  FTNPKVREWYSSLFAFPVYQGSTDILFLWNDMNEPSVFRGPEQTMQKNAIHHGNWEHREL
  HNIYGFYHQMATAEGLIKRSKGKERPFVLTRSFFAGSQKYGAVWTGDNTAEWSNLKISIP
  MLLTLSITGISFCGADIGGFIGNPETELLVRWYQAGAYQPFFRGHATMNTKRREPWLFGE
  EHTRLIREAIRERYGLLPYWYSLFYHAHVASQPVMRPLWVEFPDELKTFDMEDEYMLGSA
  LLVHPVTEPKATTVDVFLPGSNEVWYDYKTFAHWEGGCTVKIPVALDTIPVFQRGGSVIP
  IKTTVGKSTGWMTESSYGLRVALSTKGSSVGELYLDDGHSFQYLHQKQFLHRKFSFCSSV
  LINSFADQRGHYPSKCVVEKILVLGFRKEPSSVTTHSSDGKDQPVAFTYCAKTSILSLEK
  LSLNIATDWEVRII
• Function: Has alpha-glucosidase activity.
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital dyserythropoietic anemia	DIS6FAT6	Strong	Biomarker	[1]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Neutral alpha-glucosidase C (GANC).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neutral alpha-glucosidase C (GANC).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neutral alpha-glucosidase C (GANC).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Neutral alpha-glucosidase C (GANC).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Neutral alpha-glucosidase C (GANC).	[4]

References

• [1] Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. Am J Hum Genet. 2002 Dec;71(6):1467-74. doi: 10.1086/344781. Epub 2002 Nov 14.
• [2] Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder.Transl Psychiatry. 2018 Feb 2;8(1):41. doi: 10.1038/s41398-017-0088-0.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.