Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT78G2IH)

• DOT Name: Spermatogenesis-associated protein 7 (SPATA7)
• Synonyms: HSD-3.1; Spermatogenesis-associated protein HSD3
• Gene Name: SPATA7
• Related Disease:
  Cone-rod dystrophy
  Cone-rod dystrophy 2
  Leber congenital amaurosis 3
  Leber congenital amaurosis 1
  Epithelial ovarian cancer
  Leber congenital amaurosis
  Retinitis pigmentosa
  Severe early-childhood-onset retinal dystrophy
• UniProt ID: SPAT7_HUMAN
• Pfam ID: PF15244
• Sequence:
  MDGSRRVRATSVLPRYGPPCLFKGHLSTKSNAFCTDSSSLRLSTLQLVKNHMAVHYNKIL
  SAKAAVDCSVPVSVSTSIKYADQQRREKLKKELAQCEKEFKLTKTAMRANYKNNSKSLFN
  TLQKPSGEPQIEDDMLKEEMNGFSSFARSLVPSSERLHLSLHKSSKVITNGPEKNSSSSP
  SSVDYAASGPRKLSSGALYGRRPRSTFPNSHRFQLVISKAPSGDLLDKHSELFSNKQLPF
  TPRTLKTEAKSFLSQYRYYTPAKRKKDFTDQRIEAETQTELSFKSELGTAETKNMTDSEM
  NIKQASNCVTYDAKEKIAPLPLEGHDSTWDEIKDDALQHSSPRAMCQYSLKPPSTRKIYS
  DEEELLYLSFIEDVTDEILKLGLFSNRFLERLFERHIKQNKHLEEEKMRHLLHVLKVDLG
  CTSEENSVKQNDVDMLNVFDFEKAGNSEPNELKNESEVTIQQERQQYQKALDMLLSAPKD
  ENEIFPSPTEFFMPIYKSKHSEGVIIQQVNDETNLETSTLDENHPSISDSLTDRETSVNV
  IEGDSDPEKVEISNGLCGLNTSPSQSVQFSSVKGDNNHDMELSTLKIMEMSIEDCPLDV
• Function: Involved in the maintenance of both rod and cone photoreceptor cells. It is required for recruitment and proper localization of RPGRIP1 to the photoreceptor connecting cilium (CC), as well as photoreceptor-specific localization of proximal CC proteins at the distal CC. Maintenance of protein localization at the photoreceptor-specific distal CC is essential for normal microtubule stability and to prevent photoreceptor degeneration.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy	DISY9RWN	Definitive	Biomarker	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[1]
Leber congenital amaurosis 3	DIS24FTQ	Definitive	Autosomal recessive	[2]
Leber congenital amaurosis 1	DISY2B33	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[4]
Leber congenital amaurosis	DISMGH8F	Supportive	Autosomal dominant	[5]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[5]
Severe early-childhood-onset retinal dystrophy	DISFDRFO	Supportive	Autosomal recessive	[6]

17 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 Spermatogenesis-associated protein 7 (SPATA7).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Spermatogenesis-associated protein 7 (SPATA7).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Spermatogenesis-associated protein 7 (SPATA7).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[16]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Spermatogenesis-associated protein 7 (SPATA7).	[23]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Spermatogenesis-associated protein 7 (SPATA7).	[18]

References

• [1] SPATA7: Evolving phenotype from cone-rod dystrophy to retinitis pigmentosa.Ophthalmic Genet. 2016 Sep;37(3):333-8. doi: 10.3109/13816810.2015.1130154. Epub 2016 Feb 8.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Conditional loss of Spata7 in photoreceptors causes progressive retinal degeneration in mice.Exp Eye Res. 2018 Jan;166:120-130. doi: 10.1016/j.exer.2017.10.015. Epub 2017 Oct 31.
• [4] Steroid-converting enzymes in human ovarian carcinomas.Mol Cell Endocrinol. 2009 Mar 25;301(1-2):51-8. doi: 10.1016/j.mce.2008.07.015. Epub 2008 Aug 3.
• [5] Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. Am J Hum Genet. 2009 Mar;84(3):380-7. doi: 10.1016/j.ajhg.2009.02.005. Epub 2009 Mar 5.
• [6] Screening of SPATA7 in patients with Leber congenital amaurosis and severe childhood-onset retinal dystrophy reveals disease-causing mutations. Invest Ophthalmol Vis Sci. 2011 May 9;52(6):3032-8. doi: 10.1167/iovs.10-7025.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [14] 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.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [18] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [19] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.