Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFWF9N1)

• DOT Name: Bardet-Biedl syndrome 5 protein (BBS5)
• Gene Name: BBS5
• Related Disease:
  Bardet-Biedl syndrome 5
  Ciliopathy
  Cone dystrophy
  MORM syndrome
  Bardet biedl syndrome
  Glaucoma/ocular hypertension
• UniProt ID: BBS5_HUMAN
• PDB ID: 6XTB
• Pfam ID: PF07289
• Sequence:
  MSVLDALWEDRDVRFDLSAQQMKTRPGEVLIDCLDSIEDTKGNNGDRGRLLVTNLRILWH
  SLALSRVNVSVGYNCILNITTRTANSKLRGQTEALYILTKCNSTRFEFIFTNLVPGSPRL
  FTSVMAVHRAYETSKMYRDFKLRSALIQNKQLRLLPQEHVYDKINGVWNLSSDQGNLGTF
  FITNVRIVWHANMNDSFNVSIPYLQIRSIKIRDSKFGLALVIESSQQSGGYVLGFKIDPV
  EKLQESVKEINSLHKVYSASPIFGVDYEMEEKPQPLEALTVEQIQDDVEIDSDGHTDAFV
  AYFADGNKQQDREPVFSEELGLAIEKLKDGFTLQGLWEVMS
• Function: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly.
• Reactome Pathway: BBSome-mediated cargo-targeting to cilium (R-HSA-5620922)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bardet-Biedl syndrome 5	DISPXEJ4	Definitive	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[2]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[1]
MORM syndrome	DIS9NDA3	Strong	Genetic Variation	[2]
Bardet biedl syndrome	DISTBNZW	Supportive	Autosomal recessive	[3]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Bardet-Biedl syndrome 5 protein (BBS5).	[12]

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 decreases the methylation of Bardet-Biedl syndrome 5 protein (BBS5).	[11]

References

• [1] Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell. 2004 May 14;117(4):541-52. doi: 10.1016/s0092-8674(04)00450-7.
• [2] BBS5 and INPP5E mutations associated with ciliopathy disorders in families from Pakistan.Ann Hum Genet. 2019 Nov;83(6):477-482. doi: 10.1111/ahg.12336. Epub 2019 Jun 7.
• [3] Bardet-Biedl Syndrome Overview. 2003 Jul 14 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [4] Expression of CXCL6 and BBS5 that may be glaucoma relevant genes is regulated by PITX2.Gene. 2016 Nov 15;593(1):76-83. doi: 10.1016/j.gene.2016.08.019. Epub 2016 Aug 9.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.