Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBYKL89)

• DOT Name: Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B)
• Synonyms: Transmembrane activator and CAML interactor; CD antigen CD267
• Gene Name: TNFRSF13B
• Related Disease:
  Immunodeficiency, common variable, 2
  Common variable immunodeficiency
• UniProt ID: TR13B_HUMAN
• PDB ID: 1XU1; 1XUT
• Pfam ID: PF09305
• Sequence:
  MSGLGRSRRGGRSRVDQEERFPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQR
  TCAAFCRSLSCRKEQGKFYDHLLRDCISCASICGQHPKQCAYFCENKLRSPVNLPPELRR
  QRSGEVENNSDNSGRYQGLEHRGSEASPALPGLKLSADQVALVYSTLGLCLCAVLCCFLV
  AVACFLKKRGDPCSCQPRSRPRQSPAKSSQDHAMEAGSPVSTSPEPVETCSFCFPECRAP
  TQESAVTPGTPDPTCAGRWGCHTRTTVLQPCPHIPDSGLGIVCVPAQEGGPGA
• Function: Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and AP-1. Involved in the stimulation of B- and T-cell function and the regulation of humoral immunity.
• Tissue Specificity: Highly expressed in spleen, thymus, small intestine and peripheral blood leukocytes. Expressed in resting B-cells and activated T-cells, but not in resting T-cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Intesti.l immune network for IgA production (hsa04672)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway: TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency, common variable, 2	DISKL9Q6	Definitive	Autosomal recessive	[1]
Common variable immunodeficiency	DISHE7JQ	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).	[4]

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 increases the methylation of Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).	[5]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005 Aug;37(8):829-34. doi: 10.1038/ng1601. Epub 2005 Jul 10.
• [3] Identification of transcriptional biomarkers induced by SERMS in human endometrial cells using multivariate analysis of DNA microarrays. Biomarkers. 2004 Nov-Dec;9(6):447-60.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.