Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH8BT51)

• DOT Name: Synaptonemal complex central element protein 2 (SYCE2)
• Synonyms: Central element synaptonemal complex protein 1
• Gene Name: SYCE2
• Related Disease: Glutaryl-CoA dehydrogenase deficiency
• UniProt ID: SYCE2_HUMAN
• PDB ID: 6R17; 6YQF
• Sequence:
  MERQGVDVPHVKCKDQEPQPLGESKEHPRWEENCEEEAGGGPASASCQLTVLEGKSGLYF
  SSLDSSIDILQKRAQELIENINKSRQKDHALMTNFRNSLKTKVSDLTEKLEERIYQIYND
  HNKIIQEKLQEFTQKMAKISHLETELKQVCHSVETVYKDLCLQPEQSLRLRWGPDHSRGK
  SPPRPGNSQPPDVFVSSVAETTSQATASEVQTNRDGEC
• Function: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination.
• Reactome Pathway: Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glutaryl-CoA dehydrogenase deficiency	DISRAMPH	Strong	CausalMutation	[1]

5 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 Synaptonemal complex central element protein 2 (SYCE2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Synaptonemal complex central element protein 2 (SYCE2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Synaptonemal complex central element protein 2 (SYCE2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Synaptonemal complex central element protein 2 (SYCE2).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Synaptonemal complex central element protein 2 (SYCE2).	[7]

1 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 Synaptonemal complex central element protein 2 (SYCE2).	[4]

References

• [1] Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1.Biomed Res Int. 2016;2016:4074365. doi: 10.1155/2016/4074365. Epub 2016 Sep 8.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.