Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBU7CWP)

• DOT Name: Spermatogenesis-associated protein 22 (SPATA22)
• Synonyms: Testis development protein NYD-SP20
• Gene Name: SPATA22
• Related Disease:
  Canavan disease
  Female hypogonadism
• UniProt ID: SPT22_HUMAN
• Sequence:
  MKRSLNENSARSTAGCLPVPLFNQKKRNRQPLTSNPLKDDSGISTPSDNYDFPPLPTDWA
  WEAVNPELAPVMKTVDTGQIPHSVSRPLRSQDSVFNSIQSNTGRSQGGWSYRDGNKNTSL
  KTWNKNDFKPQCKRTNLVANDGKNSCPVSSGAQQQKQLRIPEPPNLSRNKETELLRQTHS
  SKISGCTMRGLDKNSALQTLKPNFQQNQYKKQMLDDIPEDNTLKETSLYQLQFKEKASSL
  RIISAVIESMKYWREHAQKTVLLFEVLAVLDSAVTPGPYYSKTFLMRDGKNTLPCVFYEI
  DRELPRLIRGRVHRCVGNYDQKKNIFQCVSVRPASVSEQKTFQAFVKIADVEMQYYINVM
  NET
• Function: Meiosis-specific protein required for homologous recombination in meiosis I.
• Tissue Specificity: Highly expressed in adult testis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Canavan disease	DIS7UPG8	Strong	Genetic Variation	[1]
Female hypogonadism	DISWASB4	Limited	Genetic Variation	[2]

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 Spermatogenesis-associated protein 22 (SPATA22).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Spermatogenesis-associated protein 22 (SPATA22).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Spermatogenesis-associated protein 22 (SPATA22).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Spermatogenesis-associated protein 22 (SPATA22).	[6]

References

• [1] Atypical clinical and radiological course of a patient with Canavan disease.Metab Brain Dis. 2016 Apr;31(2):475-9. doi: 10.1007/s11011-015-9767-9. Epub 2015 Nov 19.
• [2] A truncating MEIOB mutation responsible for familial primary ovarian insufficiency abolishes its interaction with its partner SPATA22 and their recruitment to DNA double-strand breaks.EBioMedicine. 2019 Apr;42:524-531. doi: 10.1016/j.ebiom.2019.03.075. Epub 2019 Apr 15.
• [3] 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.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] 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.
• [6] 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.