Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTXM241)

• DOT Name: GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11)
• Synonyms: EC 2.4.1.131; Asparagine-linked glycosylation protein 11 homolog; Glycolipid 2-alpha-mannosyltransferase
• Gene Name: ALG11
• Related Disease:
  ALG11-congenital disorder of glycosylation
  Congenital disorder of glycosylation
  Inborn error of metabolism
• UniProt ID: ALG11_HUMAN
• EC Number: 2.4.1.131
• Pfam ID: PF15924 ; PF00534
• Sequence:
  MAAGERSWCLCKLLRFFYSLFFPGLIVCGTLCVCLVIVLWGIRLLLQRKKKLVSTSKNGK
  NQMVIAFFHPYCNAGGGGERVLWCALRALQKKYPEAVYVVYTGDVNVNGQQILEGAFRRF
  NIRLIHPVQFVFLRKRYLVEDSLYPHFTLLGQSLGSIFLGWEALMQCVPDVYIDSMGYAF
  TLPLFKYIGGCQVGSYVHYPTISTDMLSVVKNQNIGFNNAAFITRNPFLSKVKLIYYYLF
  AFIYGLVGSCSDVVMVNSSWTLNHILSLWKVGNCTNIVYPPCDVQTFLDIPLHEKKMTPG
  HLLVSVGQFRPEKNHPLQIRAFAKLLNKKMVESPPSLKLVLIGGCRNKDDELRVNQLRRL
  SEDLGVQEYVEFKINIPFDELKNYLSEATIGLHTMWNEHFGIGVVECMAAGTIILAHNSG
  GPKLDIVVPHEGDITGFLAESEEDYAETIAHILSMSAEKRLQIRKSARASVSRFSDQEFE
  VTFLSSVEKLFK
• Function: Mannosyltransferase involved in the last steps of the synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition of the 4th and 5th mannose residues to the dolichol-linked oligosaccharide chain.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Defective ALG11 causes CDG-1p (R-HSA-4551295)
  Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (R-HSA-446193)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
ALG11-congenital disorder of glycosylation	DIS0SLL5	Strong	Autosomal recessive	[1]
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[2]
Inborn error of metabolism	DISO5FAY	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11).	[5]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase (ALG11).	[6]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] Arrest of Fetal Brain Development in ALG11-Congenital Disorder of Glycosylation.Pediatr Neurol. 2019 May;94:64-69. doi: 10.1016/j.pediatrneurol.2018.12.009. Epub 2018 Dec 24.
• [3] ALG11-CDG syndrome: Expanding the phenotype. Am J Med Genet A. 2019 Mar;179(3):498-502. doi: 10.1002/ajmg.a.61046. Epub 2019 Jan 24.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.