Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8FJMU8)

• DOT Name: Putative nucleotidyltransferase MAB21L1 (MAB21L1)
• Synonyms: EC 2.7.7.-; Protein mab-21-like 1
• Gene Name: MAB21L1
• Related Disease:
  Cerebellar, ocular, craniofacial, and genital syndrome
  Eye disorder
  Intellectual disability
  Neurodevelopmental disorder
  Neural tube defect
  Nervous system disease
• UniProt ID: MB211_HUMAN
• PDB ID: 5EOG; 5EOM
• EC Number: 2.7.7.-
• Pfam ID: PF03281 ; PF20266
• Sequence:
  MIAAQAKLVYHLNKYYNEKCQARKAAIAKTIREVCKVVSDVLKEVEVQEPRFISSLNEMD
  NRYEGLEVISPTEFEVVLYLNQMGVFNFVDDGSLPGCAVLKLSDGRKRSMSLWVEFITAS
  GYLSARKIRSRFQTLVAQAVDKCSYRDVVKMVADTSEVKLRIRDRYVVQITPAFKCTGIW
  PRSAAHWPLPHIPWPGPNRVAEVKAEGFNLLSKECHSLAGKQSSAESDAWVLQFAEAENR
  LQMGGCRKKCLSILKTLRDRHLELPGQPLNNYHMKTLVSYECEKHPRESDWDESCLGDRL
  NGILLQLISCLQCRRCPHYFLPNLDLFQGKPHSALENAAKQTWRLAREILTNPKSLEKL
• Function: Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye. It is unclear whether it displays nucleotidyltransferase activity in vivo. Binds single-stranded RNA (ssRNA).
• Tissue Specificity: Expressed in brain, cerebellum and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar, ocular, craniofacial, and genital syndrome	DISZ3R2R	Strong	Autosomal recessive	[1]
Eye disorder	DISB52BH	Strong	Biomarker	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[1]
Neural tube defect	DIS5J95E	Disputed	Genetic Variation	[2]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Putative nucleotidyltransferase MAB21L1 (MAB21L1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Putative nucleotidyltransferase MAB21L1 (MAB21L1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Putative nucleotidyltransferase MAB21L1 (MAB21L1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Putative nucleotidyltransferase MAB21L1 (MAB21L1).	[8]

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 Putative nucleotidyltransferase MAB21L1 (MAB21L1).	[7]

References

• [1] MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome). J Med Genet. 2019 May;56(5):332-339. doi: 10.1136/jmedgenet-2018-105623. Epub 2018 Nov 28.
• [2] Molecular genetic analysis of human homologs of Caenorhabditis elegans mab-21-like 1 gene in patients with neural tube defects.Birth Defects Res A Clin Mol Teratol. 2004 Nov;70(11):885-8. doi: 10.1002/bdra.20084.
• [3] Meiotic instability associated with the CAGR1 trinucleotide repeat at 13q13.J Med Genet. 1997 May;34(5):411-3. doi: 10.1136/jmg.34.5.411.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.