Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9NHGQE)

• DOT Name: Beta-defensin 126 (DEFB126)
• Synonyms: Beta-defensin 26; DEFB-26; Defensin, beta 126; Epididymal secretory protein 13.2; ESP13.2; HBD26
• Gene Name: DEFB126
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  B-cell lymphoma
  Follicular lymphoma
  Male infertility
  Non-hodgkin lymphoma
• UniProt ID: DB126_HUMAN
• Sequence:
  MKSLLFTLAVFMLLAQLVSGNWYVKKCLNDVGICKKKCKPEEMHVKNGWAMCGKQRDCCV
  PADRRANYPVFCVQTKTTRISTVTATTATTTLMMTTASMSSMAPTPVSPTG
• Function: Highly glycosylated atypical beta-defensin involved in several aspects of sperm function. Facilitates sperm transport in the female reproductive tract and contributes to sperm protection against immunodetection; both functions are probably implicating the negative surface charge provided by its O-linked oligosaccharides in the sperm glycocalyx. Involved in binding of sperm to oviductal epithelial cells to form a sperm reservoir until ovulation. Release from the sperm surface during capacitation and ovaluation by an elevation of oviductal fluid pH is unmasking other surface components and allows sperm to penetrate the cumulus matrix and bind to the zona pellucida of the oocyte. In vitro has antimicrobial activity and may inhibit LPS-mediated inflammation.
• Tissue Specificity: High-level and epididymis-specific expression. Expression is down-regulated in infertile men.
• Reactome Pathway:
  Defensins (R-HSA-1461973)
  Beta defensins (R-HSA-1461957)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[2]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[3]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Beta-defensin 126 (DEFB126).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Beta-defensin 126 (DEFB126).	[5]

References

• [1] Common variation in genes related to innate immunity and risk of adult glioma.Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1651-8. doi: 10.1158/1055-9965.EPI-08-1041.
• [2] Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma.Environ Mol Mutagen. 2013 Jan;54(1):72-7. doi: 10.1002/em.21739. Epub 2012 Oct 11.
• [3] The role of DEFB126 variation in male infertility and medically assisted reproduction technique outcome.Reprod Biomed Online. 2019 Oct;39(4):649-657. doi: 10.1016/j.rbmo.2019.05.012. Epub 2019 May 21.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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.