Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQFX76P)

• DOT Name: CBY1-interacting BAR domain-containing protein 1 (CIBAR1)
• Gene Name: CIBAR1
• Related Disease: Postaxial polydactyly type A
• UniProt ID: CBAR1_HUMAN
• Pfam ID: PF06730
• Sequence:
  MMRRTLENRNAQTKQLQTAVSNVEKHFGELCQIFAAYVRKTARLRDKADLLVNEINAYAA
  TETPHLKLGLMNFADEFAKLQDYRQAEVERLEAKVVEPLKTYGTIVKMKRDDLKATLTAR
  NREAKQLTQLERTRQRNPSDRHVISQAETELQRAAMDASRTSRHLEETINNFERQKMKDI
  KTIFSEFITIEMLFHGKALEVYTAAYQNIQNIDEDEDLEVFRNSLYAPDYSSRLDIVRAN
  SKSPLQRSLSAKCVSGTGQVSTCRLRKDQQAEDDEDDELDVTEEENFLK
• Function: Acts as a positive regulator of ciliary hedgehog signaling. Probable regulator of ciliogenesis involved in limb morphogenesis. In cooperation with CBY1 it is involved in the recruitment and fusion of endosomal vesicles at distal appendages during early stages of ciliogenesis. Plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure. In vitro, can generate membrane curvature through preferential interaction with negatively charged phospholipids such as phosphatidylinositol 4,5-bisphosphate and cardiolipin and hence orchestrate cristae shape.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Postaxial polydactyly type A	DIS4IIPW	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[8]

8 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 CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[9]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of CBY1-interacting BAR domain-containing protein 1 (CIBAR1).	[12]

References

• [1] FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice. J Bone Miner Res. 2019 Feb;34(2):375-386. doi: 10.1002/jbmr.3594. Epub 2018 Nov 5.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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.
• [9] 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.
• [10] 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.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.