Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6GBQHI)

• DOT Name: Gamma-1-syntrophin (SNTG1)
• Synonyms: G1SYN; Syntrophin-4; SYN4
• Gene Name: SNTG1
• Related Disease:
  Alzheimer disease
  Duchenne muscular dystrophy
  Schizophrenia
  Lung adenocarcinoma
  Acute myelogenous leukaemia
• UniProt ID: SNTG1_HUMAN
• PDB ID: 7PC7; 7PC8; 7QQN
• Pfam ID: PF00595
• Sequence:
  MDFRTACEETKTGICLLQDGNQEPFKVRLHLAKDILMIQEQDVICVSGEPFYSGERTVTI
  RRQTVGGFGLSIKGGAEHNIPVVVSKISKEQRAELSGLLFIGDAILQINGINVRKCRHEE
  VVQVLRNAGEEVTLTVSFLKRAPAFLKLPLNEDCACAPSDQSSGTSSPLCDSGLHLNYHP
  NNTDTLSCSSWPTSPGLRWEKRWCDLRLIPLLHSRFSQYVPGTDLSRQNAFQVIAVDGVC
  TGIIQCLSAEDCVDWLQAIATNISNLTKHNIKKINRNFPVNQQIVYMGWCEAREQDPLQD
  RVYSPTFLALRGSCLYKFLAPPVTTWDWTRAEKTFSVYEIMCKILKDSDLLDRRKQCFTV
  QSESGEDLYFSVELESDLAQWERAFQTATFLEVERIQCKTYACVLESHLMGLTIDFSTGF
  ICFDAATKAVLWRYKFSQLKGSSDDGKSKIKFLFQNPDTKQIEAKELEFSNLFAVLHCIH
  SFFAAKVACLDPLFLGNQATASTAASSATTSKAKYTT
• 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. May participate in regulating the subcellular location of diacylglycerol kinase-zeta to ensure that diacylglycerol is rapidly inactivated following receptor activation.
• Tissue Specificity: Brain specific. 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. No expression in muscle cells.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[5]

2 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-1-syntrophin (SNTG1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Gamma-1-syntrophin (SNTG1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Gamma-1-syntrophin (SNTG1).	[7]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Gamma-1-syntrophin (SNTG1).	[8]

References

• [1] Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease.Mol Neurobiol. 2019 May;56(5):3235-3243. doi: 10.1007/s12035-018-1298-z. Epub 2018 Aug 15.
• [2] SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis.Hum Genet. 2004 Jun;115(1):81-9. doi: 10.1007/s00439-004-1121-y. Epub 2004 Apr 16.
• [3] Multifaceted genomic risk for brain function in schizophrenia.Neuroimage. 2012 Jul 16;61(4):866-75. doi: 10.1016/j.neuroimage.2012.03.022. Epub 2012 Mar 13.
• [4] The genomic alterations of lung adenocarcinoma and lung squamous cell carcinoma can explain the differences of their overall survival rates.J Cell Physiol. 2019 Jul;234(7):10918-10925. doi: 10.1002/jcp.27917. Epub 2018 Dec 13.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] 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.