Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD8HJCD)

• DOT Name: Gamma-2-syntrophin (SNTG2)
• Synonyms: G2SYN; Syntrophin-5; SYN5
• Gene Name: SNTG2
• Related Disease:
  Autism
  Autism spectrum disorder
  Chronic obstructive pulmonary disease
• UniProt ID: SNTG2_HUMAN
• PDB ID: 7QQL
• Pfam ID: PF00595
• Sequence:
  MGTEGPPPPAASRGRQGCLLVPARTKTTIALLYDEESENAYDIRLKLTKEVLTIQKQDVV
  CVGGSHQGRNRRTVTLRRQPVGGLGLSIKGGSEHNVPVVISKIFEDQAADQTGMLFVGDA
  VLQVNGIHVENATHEEVVHLLRNAGDEVTITVEYLREAPAFLKLPLGSPGPSSDHSSGAS
  SPLFDSGLHLNGNSSTTAPSSPSSPIAKDPRYEKRWLDTLSVPLSMARISRYKAGTEKLR
  WNAFEVLALDGVSSGILRFYTAQDGTDWLRAVSANIRELTLQNMKMANKCCSPSDQVVHM
  GWVNEKLQGADSSQTFRPKFLALKGPSFYVFSTPPVSTFDWVRAERTYHLCEVLFKVHKF
  WLTEDCWLQANLYLGLQDFDFEDQRPYCFSIVAGHGKSHVFNVELGSELAMWEKSFQRAT
  FMEVQRTGSRTYMCSWQGEMLCFTVDFALGFTCFESKTKNVLWRFKFSQLKGSSDDGKTR
  VKLLFQNLDTKQIETKELEFQDLRAVLHCIHSFIAAKVASVDPGFMDSQSLARKYMYSS
• Function: Adapter protein that binds to and probably organizes the subcellular localization of a variety of proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex.
• Tissue Specificity: Widely expressed. Strong expression in brain and testis. In CNS, it is expressed in the perikaryon and proximal portion of the neuronal processes. Strong expression in the hippocampus, neuron-rich dendate granule cells, and pyramidal cell layers. Highly expressed in neurons of the cerebral cortex. Also expressed in the cerebellar cortex, deep cerebellar nuclei, thalamus, and basal ganglia.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Gamma-2-syntrophin (SNTG2).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Gamma-2-syntrophin (SNTG2).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Gamma-2-syntrophin (SNTG2).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Gamma-2-syntrophin (SNTG2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Gamma-2-syntrophin (SNTG2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gamma-2-syntrophin (SNTG2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Gamma-2-syntrophin (SNTG2).	[9]

References

• [1] Neuroligins 3 and 4X interact with syntrophin-gamma2, and the interactions are affected by autism-related mutations.Biochem Biophys Res Commun. 2007 Mar 30;355(1):41-6. doi: 10.1016/j.bbrc.2007.01.127. Epub 2007 Jan 31.
• [2] Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders.Genet Med. 2010 Nov;12(11):694-702. doi: 10.1097/GIM.0b013e3181f0c5f3.
• [3] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] 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.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.