Details of Drug Off-Target (DOT)

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

DOT Name POC1 centriolar protein homolog B (POC1B)
Synonyms Pix1; Proteome of centriole protein 1B; WD repeat-containing protein 51B
Gene Name POC1B
Related Disease
Cone-rod dystrophy 20 ( )
Achromatopsia ( )
Ciliopathy ( )
Cone dystrophy ( )
Cone-rod dystrophy 2 ( )
Congenital heart disease ( )
Inherited retinal dystrophy ( )
Microcephaly ( )
Night blindness ( )
Retinopathy ( )
Joubert syndrome ( )
Cone-rod dystrophy ( )
Episodic kinesigenic dyskinesia 1 ( )
Leber congenital amaurosis 1 ( )
UniProt ID
POC1B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00400
Sequence
MASATEDPVLERYFKGHKAAITSLDLSPNGKQLATASWDTFLMLWNFKPHARAYRYVGHK
DVVTSVQFSPHGNLLASASRDRTVRLWIPDKRGKFSEFKAHTAPVRSVDFSADGQFLATA
SEDKSIKVWSMYRQRFLYSLYRHTHWVRCAKFSPDGRLIVSCSEDKTIKIWDTTNKQCVN
NFSDSVGFANFVDFNPSGTCIASAGSDQTVKVWDVRVNKLLQHYQVHSGGVNCISFHPSG
NYLITASSDGTLKILDLLEGRLIYTLQGHTGPVFTVSFSKGGELFASGGADTQVLLWRTN
FDELHCKGLTKRNLKRLHFDSPPHLLDIYPRTPHPHEEKVETVEINPKLEVIDLQISTPP
VMDILSFDSTTTTETSGRTLPDKGEEACGYFLNPSLMSPECLPTTTKKKTEDMSDLPCES
QRSIPLAVTDALEHIMEQLNVLTQTVSILEQRLTLTEDKLKDCLENQQKLFSAVQQKS
Function
Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1A to ensure centriole integrity and proper mitotic spindle formation. Required for primary cilia formation, ciliary length and also cell proliferation. Required for retinal integrity.
Tissue Specificity Expressed in the retina.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cone-rod dystrophy 20 DISSTSLH Definitive Autosomal recessive [1]
Achromatopsia DISKL51I Strong Genetic Variation [2]
Ciliopathy DIS10G4I Strong Biomarker [3]
Cone dystrophy DIS7SAZZ Strong Biomarker [4]
Cone-rod dystrophy 2 DISX2RWY Strong Genetic Variation [5]
Congenital heart disease DISQBA23 Strong CausalMutation [6]
Inherited retinal dystrophy DISGGL77 Strong Genetic Variation [3]
Microcephaly DIS2GRD8 Strong CausalMutation [6]
Night blindness DIS335K9 Strong Biomarker [6]
Retinopathy DISB4B0F Strong Biomarker [4]
Joubert syndrome DIS7P5CO moderate Biomarker [5]
Cone-rod dystrophy DISY9RWN Supportive Autosomal dominant [1]
Episodic kinesigenic dyskinesia 1 DISGVQMP Limited Biomarker [7]
Leber congenital amaurosis 1 DISY2B33 Limited Genetic Variation [8]
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⏷ Show the Full List of 14 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of POC1 centriolar protein homolog B (POC1B). [9]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of POC1 centriolar protein homolog B (POC1B). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of POC1 centriolar protein homolog B (POC1B). [11]
Bortezomib DMNO38U Approved Bortezomib increases the expression of POC1 centriolar protein homolog B (POC1B). [12]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol affects the expression of POC1 centriolar protein homolog B (POC1B). [13]
Genistein DM0JETC Phase 2/3 Genistein affects the expression of POC1 centriolar protein homolog B (POC1B). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of POC1 centriolar protein homolog B (POC1B). [14]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of POC1 centriolar protein homolog B (POC1B). [15]
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⏷ Show the Full List of 8 Drug(s)

References

1 Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy. Am J Hum Genet. 2014 Aug 7;95(2):131-42. doi: 10.1016/j.ajhg.2014.06.012. Epub 2014 Jul 10.
2 Case of cone dystrophy with normal fundus appearance associated with biallelic POC1B variants.Ophthalmic Genet. 2018 Apr;39(2):255-262. doi: 10.1080/13816810.2017.1408846. Epub 2017 Dec 8.
3 Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish.Biochem Biophys Res Commun. 2015 Oct 2;465(4):651-7. doi: 10.1016/j.bbrc.2015.06.083. Epub 2015 Jul 15.
4 Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3432-3446. doi: 10.1167/iovs.19-26650.
5 Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.Ophthalmic Genet. 2018 Jun;39(3):300-306. doi: 10.1080/13816810.2018.1430239. Epub 2018 Jan 29.
6 Novel recessive cone-rod dystrophy caused by POC1B mutation.JAMA Ophthalmol. 2014 Oct;132(10):1185-91. doi: 10.1001/jamaophthalmol.2014.1658.
7 Analysis of catechol-O-methyltransferase gene mutation and identification of new pathogenic gene for paroxysmal kinesigenic dyskinesia.Neurol Sci. 2016 Mar;37(3):377-83. doi: 10.1007/s10072-015-2432-6. Epub 2015 Dec 9.
8 Mutation of POC1B in a severe syndromic retinal ciliopathy.Hum Mutat. 2014 Oct;35(10):1153-62. doi: 10.1002/humu.22618. Epub 2014 Aug 11.
9 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.
10 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
13 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
14 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.
15 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.