Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1TTWX)

• DOT Name: Bardet-Biedl syndrome 10 protein (BBS10)
• Gene Name: BBS10
• Related Disease:
  Bardet-Biedl syndrome 10
  Ciliopathy
  Nijmegen breakage syndrome
  Non-insulin dependent diabetes
  Obesity
  Polydactyly
  Retinitis pigmentosa
  Bardet biedl syndrome
• UniProt ID: BBS10_HUMAN
• Pfam ID: PF00118
• Sequence:
  MLSSMAAAGSVKAALQVAEVLEAIVSCCVGPEGRQVLCTKPTGEVLLSRNGGRLLEALHL
  EHPIARMIVDCVSSHLKKTGDGAKTFIIFLCHLLRGLHAITDREKDPLMCENIQTHGRHW
  KNCSRWKFISQALLTFQTQILDGIMDQYLSRHFLSIFSSAKERTLCRSSLELLLEAYFCG
  RVGRNNHKFISQLMCDYFFKCMTCKSGIGVFELVDDHFVELNVGVTGLPVSDSRIIAGLV
  LQKDFSVYRPADGDMRMVIVTETIQPLFSTSGSEFILNSEAQFQTSQFWIMEKTKAIMKH
  LHSQNVKLLISSVKQPDLVSYYAGVNGISVVECLSSEEVSLIRRIIGLSPFVPPQAFSQC
  EIPNTALVKFCKPLILRSKRYVHLGLISTCAFIPHSIVLCGPVHGLIEQHEDALHGALKM
  LRQLFKDLDLNYMTQTNDQNGTSSLFIYKNSGESYQAPDPGNGSIQRPYQDTVAENKDAL
  EKTQTYLKVHSNLVIPDVELETYIPYSTPTLTPTDTFQTVETLTCLSLERNRLTDYYEPL
  LKNNSTAYSTRGNRIEISYENLQVTNITRKGSMLPVSCKLPNMGTSQSYLSSSMPAGCVL
  PVGGNFEILLHYYLLNYAKKCHQSEETMVSMIIANALLGIPKVLYKSKTGKYSFPHTYIR
  AVHALQTNQPLVSSQTGLESVMGKYQLLTSVLQCLTKILTIDMVITVKRHPQKVHNQDSE
  DEL
• Function: Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis. Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation.
• Reactome Pathway: BBSome-mediated cargo-targeting to cilium (R-HSA-5620922)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bardet-Biedl syndrome 10	DIS7KV1E	Definitive	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Definitive	Autosomal recessive	[1]
Nijmegen breakage syndrome	DIS98HVL	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Polydactyly	DIS25BMZ	Strong	Genetic Variation	[4]
Retinitis pigmentosa	DISCGPY8	Strong	CausalMutation	[2]
Bardet biedl syndrome	DISTBNZW	Supportive	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Bardet-Biedl syndrome 10 protein (BBS10).	[17]

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 Bardet-Biedl syndrome 10 protein (BBS10).	[14]

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] BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006 May;38(5):521-4. doi: 10.1038/ng1771. Epub 2006 Apr 2.
• [3] A novel test for recessive contributions to complex diseases implicates Bardet-Biedl syndrome gene BBS10 in idiopathic type 2 diabetes and obesity.Am J Hum Genet. 2014 Nov 6;95(5):509-20. doi: 10.1016/j.ajhg.2014.09.015. Epub 2014 Oct 16.
• [4] BBS10 mutations are common in 'Meckel'-type cystic kidneys. J Med Genet. 2010 Dec;47(12):848-52. doi: 10.1136/jmg.2010.079392. Epub 2010 Aug 30.
• [5] Novel homozygous mutations in the genes ARL6 and BBS10 underlying Bardet-Biedl syndrome. Gene. 2013 Feb 15;515(1):84-8. doi: 10.1016/j.gene.2012.11.023. Epub 2012 Dec 6.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.