Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTOIXW8)

• DOT Name: Synaptonemal complex central element protein 1 (SYCE1)
• Synonyms: Cancer/testis antigen 76; CT76
• Gene Name: SYCE1
• Related Disease:
  Neoplasm
  Premature ovarian failure 12
  Spermatogenic failure 15
  Trichohepatoenteric syndrome
  Acute myelogenous leukaemia
  Female hypogonadism
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
• UniProt ID: SYCE1_HUMAN
• Pfam ID: PF15233
• Sequence:
  MAGRSLTSKAEPTAGAVDRAEKAGGQDTSSQKIEDLMEMVQKLQKVGSLEPRVEVLINRI
  NEVQQAKKKANKDLGEARTICEALQKELDSLHGEKVHLKEILSKKQETLRILRLHCQEKE
  SEAHRKHTMLQECKERISALNLQIEEEKNKQRQLRLAFEEQLEDLMGQHKDLWDFHMPER
  LAKEICALDSSKEQLLKEEKLVKATLEDVKHQLCSLCGAEGPSTLDEGLFLRSQEAAATV
  QLFQEEHRKAEELLAAAAQRHQQLQQKCQQQQQKRQRLKEELEKHGMQVPAQAQSTQEEE
  AGPGDVASPKPLKGERPGAAHQAGPDVLIGQEDTLHPDLSPRGFQEIKELF
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Premature ovarian failure 12	DISB95JB	Strong	Autosomal recessive	[2]
Spermatogenic failure 15	DIS7VM5V	Strong	Autosomal recessive	[3]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[5]
Female hypogonadism	DISWASB4	moderate	Biomarker	[6]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Supportive	Autosomal dominant	[7]

2 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 Synaptonemal complex central element protein 1 (SYCE1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Synaptonemal complex central element protein 1 (SYCE1).	[9]

References

• [1] A search for novel cancer/testis antigens in lung cancer identifies VCX/Y genes, expanding the repertoire of potential immunotherapeutic targets.Cancer Res. 2014 Sep 1;74(17):4694-705. doi: 10.1158/0008-5472.CAN-13-3725. Epub 2014 Jun 26.
• [2] A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet. 2011 May;7(5):e1002088. doi: 10.1371/journal.pgen.1002088. Epub 2011 May 26.
• [3] The role of prostaglandins in parturition, with special reference to the rat. Ciba Found Symp. 1977;(47):297-318. doi: 10.1002/9780470720295.ch12.
• [4] Germline genes hypomethylation and expression define a molecular signature in peripheral blood of ICF patients: implications for diagnosis and etiology.Orphanet J Rare Dis. 2014 Apr 17;9:56. doi: 10.1186/1750-1172-9-56.
• [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] Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases.Hum Reprod. 2016 Aug;31(8):1913-25. doi: 10.1093/humrep/dew142. Epub 2016 Jun 14.
• [7] Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia. J Assist Reprod Genet. 2015 Jun;32(6):887-91. doi: 10.1007/s10815-015-0445-y. Epub 2015 Apr 22.
• [8] 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.
• [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.