Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUBPEJ6)

• DOT Name: Primary cilium assembly protein FAM149B1 (FAM149B1)
• Gene Name: FAM149B1
• Related Disease:
  Ciliopathy
  Joubert syndrome 36
  Orofaciodigital syndrome I
  Joubert syndrome
  Orofaciodigital syndrome
  Orofaciodigital syndrome type 6
• UniProt ID: F149B_HUMAN
• Pfam ID: PF12516
• Sequence:
  MISRYTRKAVPQSLELKGITKHALNHHPPPEKLEEISPTSDSHEKDTSSQSKSDITRESS
  FTSADTGNSLSAFPSYTGAGISTEGSSDFSWGYGELDQNATEKVQTMFTAIDELLYEQKL
  SVHTKSLQEECQQWTASFPHLRILGRQIITPSEGYRLYPRSPSAVSASYETTLSQERDST
  IFGIRGKKLHFSSSYAHKASSIAKSSSFCSMERDEEDSIIVSEGIIEEYLAFDHIDIEEG
  FHGKKSEAATEKQKLGYPPIAPFYCMKEDVLAYVFDSVWCKVVSCMEQLTRSHWEGFASD
  DESNVAVTRPDSESSCVLSELHPLVLPRVPQSKVLYITSNPMSLCQASRHQPNVNDLLVH
  GMPLQPRNLSLMDKLLDLDDKLLMRPGSSTILSTRNWPNRAVEFSTSSLSYTVQSTRRRN
  PPPRTLHPISTSHSCAETPRSVEEILRGARVPVAPDSLSSPSPTPLSRNNLLPPIGTAEV
  EHVSTVGPQRQMKPHGDSSRAQSAVVDEPNYQQPQERLLLPDFFPRPNTTQSFLLDTQYR
  RSCAVEYPHQARPGRGSAGPQLHGSTKSQSGGRPVSRTRQGP
• Function: Involved in the localization of proteins to the cilium and cilium assembly. Indirectly regulates the signaling functions of the cilium, being required for normal SHH/smoothened signaling and proper development.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliopathy	DIS10G4I	Strong	Biomarker	[1]
Joubert syndrome 36	DISIWDGC	Strong	Autosomal recessive	[1]
Orofaciodigital syndrome I	DIST27XL	Strong	Genetic Variation	[1]
Joubert syndrome	DIS7P5CO	moderate	Biomarker	[1]
Orofaciodigital syndrome	DISSB296	moderate	Genetic Variation	[1]
Orofaciodigital syndrome type 6	DISQY7K4	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[11]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Primary cilium assembly protein FAM149B1 (FAM149B1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Primary cilium assembly protein FAM149B1 (FAM149B1).	[4]

References

• [1] Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans. Am J Hum Genet. 2019 Apr 4;104(4):731-737. doi: 10.1016/j.ajhg.2019.02.018. Epub 2019 Mar 21.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.