Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUSRSB5)

• DOT Name: Photoreceptor cilium actin regulator (PCARE)
• Gene Name: PCARE
• Related Disease:
  Cone-rod dystrophy
  Cone-rod dystrophy 2
  PCARE-related retinopathy
  Retinitis pigmentosa 54
  Breast cancer
  Breast carcinoma
  Inherited retinal dystrophy
  Stargardt disease
  Usher syndrome
  Retinopathy
  Sensorineural hearing loss disorder
  Retinitis pigmentosa
• UniProt ID: PCARE_HUMAN
• PDB ID: 7LXF
• Pfam ID: PF15449
• Sequence:
  MGCTPSHSDLVNSVAKSGIQFLKKPKAIRPGCQGGSERGSIPLLVKNSTCYDAGEGLAEE
  QPSPRRNQTTAKGLCQLMGDPASGKRKDMEGLIPGTKTSSSQLNKSQSHMAKDIPFKTQG
  SHGSQGADFSGDESEESSTQDTSKWKRTAKCHTSSTQSHCYQTIHPAHEPEGKVDFPEPL
  VKAHQQAYTYLHSSLSKYEAILCIIHQATQTRELLQPMVSFLLLCFEEISQLLGEISKDG
  EVLLQEVREDLAWPLKKREPQEQPNLLQQLLQYTVSKLQVLNGTVASLTGSFLEGSSSYL
  HSTATHLENKLSTKRNVDERLLRALRQLESLASGCGDPGVQGLPLCSEDSGIGADNESVQ
  SVDKLGKQTSWDLAPEPEEWKSVTSPHTEARQSGHTWQQSPFCLGSGRPQDCLLSGAPMA
  KVQPRAQDEARSPCLSSTSPENITSPPLKLGTSTPCDSFGIGVSVEPHLSKTSRPMDASS
  LSDSEDSSPEEEEEDKMSSMSLCAWQEKTPHSRPQSSPADRESPFQARTRRLRSLQAQEM
  ILKMKESISERIKFVPVPCGHQDWSEEEEGRTVVPPRPSTVSGSRRAPERQTRSQSESCL
  QSHVEDPTFQELRRVQRDLSQKLEAFYALGAKGQGQSQEQILQPRAAAVWPNGTCRVSPS
  NTTSRLKASLTKNFSILPSQDKSILQKCNPHPEDEQGKAGKLPNAIPSGEVSEAAKATDW
  NVRGCPTRTSVKKLIETFSPTESLRMLGDSKDAGASPCLRNCIMPPRFPKYTGLAPLYPK
  PQISPASGRESLKMGIGWKPLAPIFPPLPKAEAAKSEELSCEMEGNLEHLPPPPMEVLMD
  KSFASLESPESSKSTENSPKETQEPGPGEAGPTRRTWASPKLRASVSPLDLLPSKSTASL
  TKPHSTGPGSGRSSCQPRKPALDLSSPPATSQSPEVKGGTWSQAEKATSLYRQPRKAIAW
  HHSGPPSGQNRTSESSLARPRQSRERSPPVGRKASPTRTHWVPQADKRRRSLPSSYRPAQ
  PSPSAVQTPPSPPVSPRVLSPPTTKRRTSPPHQPKLPNPPPESAPAQCKVPSPPTQHPEA
  SPPFSIPSPSPPMSPSQEHKETRDSEDSQAVIAKVSGNTHSIFCPATSSLFEAKPPLSTA
  HPLTPPSLPPEAGGPLGNPAECWKNSSGPWLRADSQRRAALCALNPLPFLRRTASDRQPG
  GRPQPPTLDPTSTSYESQLGQNSSSEESPKKDTEPGSSPCSPELQGGTRRASPPEFCVLG
  HGLQPEPRTGHIQDKSQPEAQPQQEEVS
• Function: Plays an essential role for normal photoreceptor cell maintenance and vision.
• Tissue Specificity: Specifically expressed in retina.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy	DISY9RWN	Definitive	Genetic Variation	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Genetic Variation	[1]
PCARE-related retinopathy	DISBOJH1	Definitive	Autosomal recessive	[2]
Retinitis pigmentosa 54	DIS4N65W	Definitive	Autosomal recessive	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Inherited retinal dystrophy	DISGGL77	Strong	CausalMutation	[3]
Stargardt disease	DISPXOTO	Strong	Genetic Variation	[5]
Usher syndrome	DIS9YIS7	Strong	Genetic Variation	[6]
Retinopathy	DISB4B0F	moderate	Genetic Variation	[7]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[6]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Photoreceptor cilium actin regulator (PCARE).	[9]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Photoreceptor cilium actin regulator (PCARE).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Photoreceptor cilium actin regulator (PCARE).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Photoreceptor cilium actin regulator (PCARE).	[10]

2 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 increases the methylation of Photoreceptor cilium actin regulator (PCARE).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Photoreceptor cilium actin regulator (PCARE).	[13]

References

• [1] C2orf71a/pcare1 is important for photoreceptor outer segment morphogenesis and visual function in zebrafish.Sci Rep. 2018 Jun 26;8(1):9675. doi: 10.1038/s41598-018-27928-7.
• [2] 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.
• [3] Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71. Am J Hum Genet. 2010 May 14;86(5):686-95. doi: 10.1016/j.ajhg.2010.03.005. Epub 2010 Apr 15.
• [4] Analysis of the miRNA-mRNA-lncRNA network in human estrogen receptor-positive and estrogen receptor-negative breast cancer based on TCGA data.Gene. 2018 Jun 5;658:28-35. doi: 10.1016/j.gene.2018.03.011. Epub 2018 Mar 5.
• [5] Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.PLoS One. 2014 Dec 29;9(12):e116176. doi: 10.1371/journal.pone.0116176. eCollection 2014.
• [6] A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome. J Med Genet. 2014 Jul;51(7):460-9. doi: 10.1136/jmedgenet-2014-102287. Epub 2014 Apr 29.
• [7] C2orf71 Mutations as a Frequent Cause of Autosomal-Recessive Retinitis Pigmentosa: Clinical Analysis and Presentation of 8 Novel Mutations.Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3840-3850. doi: 10.1167/iovs.17-21597.
• [8] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.