Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVK4VMH)

• DOT Name: Myogenesis-regulating glycosidase (MYORG)
• Synonyms: EC 3.2.1.-; Uncharacterized family 31 glucosidase KIAA1161
• Gene Name: MYORG
• Related Disease:
  Basal ganglia calcification, idiopathic, 7, autosomal recessive
  Dystonia
  Bilateral striopallidodentate calcinosis
• UniProt ID: MYORG_HUMAN
• PDB ID: 7QQF; 7QQG; 7QQH
• EC Number: 3.2.1.-
• Pfam ID: PF01055 ; PF21365
• Sequence:
  MLQNPQEKSQAYPRRRRPGCYAYRQNPEAIAAAAMYTFLPDNFSPAKPKPSKDLKPLLGS
  AVLGLLLVLAAVVAWCYYSVSLRKAERLRAELLDLKAGGFSIRNQKGEQVFRLAFRSGAL
  DLDSCSRDGALLGCSLTADGLPLHFFIQTVRPKDTVMCYRVRWEEAAPGRAVEHAMFLGD
  AAAHWYGGAEMRTQHWPIRLDGQQEPQPFVTSDVYSSDAAFGGILERYWLSSRAAAIKVN
  DSVPFHLGWNSTERSLRLQARYHDTPYKPPAGRAAAPELSYRVCVGSDVTSIHKYMVRRY
  FNKPSRVPAPEAFRDPIWSTWALYGRAVDQDKVLRFAQQIRLHHFNSSHLEIDDMYTPAY
  GDFDFDEVKFPNASDMFRRLRDAGFRVTLWVHPFVNYNSSRFGEGVERELFVREPTGRLP
  ALVRWWNGIGAVLDFTHPKARDWFQGHLRRLRSRYSVASFKFDAGEVSYLPRDFSTYRPL
  PDPSVWSRRYTEMALPFFSLAEVRVGYQSQNISCFFRLVDRDSVWGYDLGLRSLIPAVLT
  VSMLGYPFILPDMVGGNAVPQRTAGGDVPERELYIRWLEVAAFMPAMQFSIPPWRYDAEV
  VAIAQKFAALRASLVAPLLLELAGEVTDTGDPIVRPLWWIAPGDETAHRIDSQFLIGDTL
  LVAPVLEPGKQERDVYLPAGKWRSYKGELFDKTPVLLTDYPVDLDEIAYFTWAS
• Function: Putative glycosidase. Promotes myogenesis by activating AKT signaling through the maturation and secretion of IGF2.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Basal ganglia calcification, idiopathic, 7, autosomal recessive	DISU86UI	Definitive	Autosomal recessive	[1]
Dystonia	DISJLFGW	Strong	Biomarker	[2]
Bilateral striopallidodentate calcinosis	DISNZJTB	Supportive	Autosomal dominant	[3]

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 Myogenesis-regulating glycosidase (MYORG).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Myogenesis-regulating glycosidase (MYORG).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Myogenesis-regulating glycosidase (MYORG).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the expression of Myogenesis-regulating glycosidase (MYORG).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Myogenesis-regulating glycosidase (MYORG).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Myogenesis-regulating glycosidase (MYORG).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myogenesis-regulating glycosidase (MYORG).	[9]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Myogenesis-regulating glycosidase (MYORG).	[6]

References

• [1] Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification. Neuron. 2018 Jun 27;98(6):1116-1123.e5. doi: 10.1016/j.neuron.2018.05.037. Epub 2018 Jun 14.
• [2] Biallelic MYORG mutation carriers exhibit primary brain calcification with a distinct phenotype.Brain. 2019 Jun 1;142(6):1573-1586. doi: 10.1093/brain/awz095.
• [3] A biallelic mutation links MYORG to autosomal-recessive primary familial brain calcification. Brain. 2019 Feb 1;142(2):e4. doi: 10.1093/brain/awy343.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.