Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5SS4P8)

• DOT Name: B9 domain-containing protein 2 (B9D2)
• Synonyms: MKS1-related protein 2
• Gene Name: B9D2
• Related Disease:
  Colorectal carcinoma
  Meckel syndrome, type 10
  Polydactyly
  Ciliopathy
  Meckel syndrome
  Joubert syndrome
• UniProt ID: B9D2_HUMAN
• Pfam ID: PF07162
• Sequence:
  MAEVHVIGQIIGASGFSESSLFCKWGIHTGAAWKLLSGVREGQTQVDTPQIGDMAYWSHP
  IDLHFATKGLQGWPRLHFQVWSQDSFGRCQLAGYGFCHVPSSPGTHQLACPTWRPLGSWR
  EQLARAFVGGGPQLLHGDTIYSGADRYRLHTAAGGTVHLEIGLLLRNFDRYGVEC
• Function: Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Meckel syndrome, type 10	DIS5DO84	Strong	Autosomal recessive	[2]
Polydactyly	DIS25BMZ	Strong	Biomarker	[3]
Ciliopathy	DIS10G4I	Moderate	Autosomal recessive	[4]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[2]
Joubert syndrome	DIS7P5CO	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of B9 domain-containing protein 2 (B9D2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of B9 domain-containing protein 2 (B9D2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of B9 domain-containing protein 2 (B9D2).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of B9 domain-containing protein 2 (B9D2).	[7]

References

• [1] Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.Nat Genet. 2014 Jun;46(6):533-42. doi: 10.1038/ng.2985. Epub 2014 May 18.
• [2] Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am J Hum Genet. 2011 Jul 15;89(1):94-110. doi: 10.1016/j.ajhg.2011.06.003.
• [3] Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] 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.