Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMK3QIS)

• DOT Name: Sperm protein associated with the nucleus on the X chromosome A (SPANXA1)
• Synonyms: Cancer/testis antigen 11.1; CT11.1; Nuclear-associated protein SPAN-Xa; SPAN-X; SPANX-A; SPANX family member A
• Gene Name: SPANXA1
• Related Disease:
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Acute myelogenous leukaemia
  Advanced cancer
  Germ cell tumor
  Neoplasm
  Plasma cell myeloma
  Seminoma
  Skin neoplasm
  Small lymphocytic lymphoma
  Testicular cancer
  Testicular germ cell tumor
  Uveal Melanoma
  Melanoma
  Prostate cancer
  Prostate carcinoma
  Colorectal carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
• UniProt ID: SPNXA_HUMAN
• Pfam ID: PF07458
• Sequence:
  MDKQSSAGGVKRSVPCDSNEANEMMPETPTGDSDPQPAPKKMKTSESSTILVVRYRRNFK
  RTSPEELLNDHARENRINPLQMEEEEFMEIMVEIPAK
• Tissue Specificity: Detected in testis and sperm.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid cancer	DIS3VLDH	Definitive	Biomarker	[1]
Thyroid gland carcinoma	DISMNGZ0	Definitive	Biomarker	[1]
Thyroid tumor	DISLVKMD	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Germ cell tumor	DIS62070	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[5]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[6]
Skin neoplasm	DIS16DDV	Strong	Biomarker	[7]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[2]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[8]
Testicular germ cell tumor	DIS5RN24	Strong	Altered Expression	[4]
Uveal Melanoma	DISA7ZGL	Strong	Altered Expression	[9]
Melanoma	DIS1RRCY	moderate	Biomarker	[10]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[8]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[12]
Lung cancer	DISCM4YA	Limited	Biomarker	[12]
Lung carcinoma	DISTR26C	Limited	Biomarker	[12]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Sperm protein associated with the nucleus on the X chromosome A (SPANXA1) affects the response to substance of Fluorouracil.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Sperm protein associated with the nucleus on the X chromosome A (SPANXA1).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Sperm protein associated with the nucleus on the X chromosome A (SPANXA1).	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Sperm protein associated with the nucleus on the X chromosome A (SPANXA1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sperm protein associated with the nucleus on the X chromosome A (SPANXA1).	[16]

References

• [1] Iodine promotes thyroid cancer development via SPANXA1 through the PI3K/AKT signalling pathway.Oncol Lett. 2019 Jul;18(1):637-644. doi: 10.3892/ol.2019.10391. Epub 2019 May 21.
• [2] Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies.Blood. 2003 Feb 1;101(3):955-60. doi: 10.1182/blood-2002-06-1930. Epub 2002 Aug 22.
• [3] Cancer/testis antigens trigger epithelial-mesenchymal transition and genesis of cancer stem-like cells.Curr Pharm Des. 2015;21(10):1292-300. doi: 10.2174/1381612821666141211154707.
• [4] Expression of SpanX mRNA in testicular germ cell tumors.Hum Cell. 2006 Aug;19(3):87-90. doi: 10.1111/j.1749-0774.2006.00014.x.
• [5] SPAN-Xb expression in myeloma cells is dependent on promoter hypomethylation and can be upregulated pharmacologically.Int J Cancer. 2006 Mar 15;118(6):1436-44. doi: 10.1002/ijc.21499.
• [6] Expression of SpanX proteins in normal testes and in testicular germ cell tumours.Int J Androl. 2006 Apr;29(2):368-73. doi: 10.1111/j.1365-2605.2005.00615.x. Epub 2005 Dec 22.
• [7] Genomic organization, incidence, and localization of the SPAN-x family of cancer-testis antigens in melanoma tumors and cell lines.Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):101-12. doi: 10.1158/1078-0432.ccr-0647-3.
• [8] Mutational analysis of SPANX genes in families with X-linked prostate cancer.Prostate. 2007 Jun 1;67(8):820-8. doi: 10.1002/pros.20561.
• [9] Immunoexpression of SPANX-C in metastatic uveal melanoma.Pathol Res Pract. 2019 Jul;215(7):152431. doi: 10.1016/j.prp.2019.04.023. Epub 2019 Apr 29.
• [10] SPANX-B and SPANX-C (Xq27 region) gene dosage analysis in Sicilian patients with melanoma.Melanoma Res. 2008 Aug;18(4):295-9. doi: 10.1097/CMR.0b013e32830aaa90.
• [11] Cancer/testis antigens and clinical risk factors for liver metastasis of colorectal cancer: a predictive panel.Dis Colon Rectum. 2010 Jan;53(1):31-8. doi: 10.1007/DCR.0b013e3181bdca3a.
• [12] SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma.Oncotarget. 2016 Jul 12;7(28):44417-44429. doi: 10.18632/oncotarget.10088.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [15] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [16] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.