Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3DKIYB)

• DOT Name: Stimulated by retinoic acid gene 8 protein homolog (STRA8)
• Gene Name: STRA8
• Related Disease:
  Azoospermia
  Oligospermia
  Vitamin A deficiency
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
  Cryptorchidism
• UniProt ID: STRA8_HUMAN
• Sequence:
  MGKIDVDKILFFNQEIRLWQLIMATPEENSNPHDRATPQLPAQLQELEHRVARRRLSQAR
  HRATLAALFNNLRKTVYSQSDLIASKWQVLNKAKSHIPELEQTLDNLLKLKASFNLEDGH
  ASSLEEVKKEYASMYSGNDSFPQNGSSPWYLNFYKQTMDLLTGSGIITPQEAALPIVSAA
  ISHLWQNLSEERKASLRQAWAQKHRGPATLAEACREPACAEGSVKDSGVDSQGASCSLVS
  TPEEILFEDAFDVASFLDKSEVPSTSSSSSVLASCNPENPEEKFQLYMQIINFFKGLSCA
  NTQVKQEASFPVDEEMIMLQCTETFDDEDL
• Function: Meiosis-inducer required for the transition into meiosis for both female and male germ cells. In female germ cells, acts downstream of ZGLP1 as a key effector of the meiotic program: required for premeiotic DNA replication and subsequent events in meiotic prophase. During spermatogenesis, next to its role in meiotic initiation, promotes (but is not required for) spermatogonial differentiation. In complex with MEIOSIN, directly activates the transcription of a subset of critical meiotic genes playing a central role in cell-cycle switching from mitosis to meiosis.
• Tissue Specificity: Expressed specifically in testis and fetal ovaries.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Genetic Variation	[1]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[1]
Vitamin A deficiency	DISBEPZO	Strong	Biomarker	[2]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Moderate	Autosomal recessive	[3]
Cryptorchidism	DISYUD2P	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Stimulated by retinoic acid gene 8 protein homolog (STRA8).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Stimulated by retinoic acid gene 8 protein homolog (STRA8).	[6]

References

• [1] Genetic variants in meiotic program initiation pathway genes are associated with spermatogenic impairment in a Han Chinese population.PLoS One. 2013;8(1):e53443. doi: 10.1371/journal.pone.0053443. Epub 2013 Jan 8.
• [2] Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling pathway.Int J Mol Med. 2018 Nov;42(5):2819-2830. doi: 10.3892/ijmm.2018.3825. Epub 2018 Aug 14.
• [3] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [4] Effects of body temperature on the expression and localization of meiosis-related proteins STRA8 and SCP3 in boar testes.Acta Histochem. 2019 Aug;121(6):718-723. doi: 10.1016/j.acthis.2019.06.007. Epub 2019 Jun 26.
• [5] Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. PLoS One. 2011;6(6):e20249. doi: 10.1371/journal.pone.0020249. Epub 2011 Jun 3.
• [6] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.