Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ORXCM)

• DOT Name: Cadherin-related family member 1 (CDHR1)
• Synonyms: Photoreceptor cadherin; prCAD; Protocadherin-21
• Gene Name: CDHR1
• Related Disease:
  Cone-rod dystrophy 15
  Age-related macular degeneration
  Carcinoid tumor
  Cone dystrophy
  Macular degeneration
  Choroidal dystrophy
  Cone-rod dystrophy
  Retinitis pigmentosa
  Blindness
  Cone-rod dystrophy 2
  Inherited retinal dystrophy
  Leber congenital amaurosis
• UniProt ID: CDHR1_HUMAN
• Pfam ID: PF00028
• Sequence:
  MRRCRWAALALGLLRLCLAQANFAPHFFDNGVGSTNGNMALFSLPEDTPVGSHVYTLNGT
  DPEGDPISYHISFDPSTRSVFSVDPTFGNITLVEELDREREDEIEAIISISDGLNLVAEK
  VVILVTDANDEAPRFIQEPYVALVPEDIPAGSIIFKVHAVDRDTGSGGSVTYFLQNLHSP
  FAVDRHSGVLRLQAGATLDYERSRTHYITVVAKDGGGRLHGADVVFSATTTVTVNVEDVQ
  DMAPVFVGTPYYGYVYEDTLPGSEVLKVVAMDGDRGKPNRILYSLVNGNDGAFEINETSG
  AISITQSPAQLQREVYELHVQVTEMSPAGSPAAQATVPVTIRIVDLNNHPPTFYGESGPQ
  NRFELSMNEHPPQGEILRGLKITVNDSDQGANAKFNLQLVGPRGIFRVVPQTVLNEAQVT
  IIVENSAAIDFEKSKVLTFKLLAVEVNTPEKFSSTADVVIQLLDTNDNVPKFDSLYYVAR
  IPENAPGGSSVVAVTAVDPDTGPWGEVKYSTYGTGADLFLIHPSTGLIYTQPWASLDAEA
  TARYNFYVKAEDMEGKYSVAEVFITLLDVNDHPPQFGKSVQKKTMVLGTPVKIEAIDEDA
  EEPNNLVDYSITHAEPANVFDINSHTGEIWLKNSIRSLDALHNITPGRDCLWSLEVQAKD
  RGSPSFSTTALLKIDITDAETLSRSPMAAFLIQTKDNPMKAVGVLAGTMATVVAITVLIS
  TATFWRNKKSNKVLPMRRVLRKRPSPAPRTIRIEWLKSKSTKAATKFMLKEKPPNENCNN
  NSPESSLLPRAPALPPPPSVAPSTGAAQWTVPTVSGSLTPQPTQPPPKPKTMGSPVQSTL
  ISELKQKFEKKSVHNKAYF
• Function: Potential calcium-dependent cell-adhesion protein. May be required for the structural integrity of the outer segment (OS) of photoreceptor cells.

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 15	DISUYAHP	Definitive	Autosomal recessive	[1]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[2]
Carcinoid tumor	DISMNRDC	Strong	Altered Expression	[3]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[4]
Macular degeneration	DISLKKHD	Strong	Biomarker	[2]
Choroidal dystrophy	DISWIF1T	moderate	Genetic Variation	[5]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[6]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[7]
Blindness	DISTIM10	Limited	Genetic Variation	[8]
Cone-rod dystrophy 2	DISX2RWY	Limited	Genetic Variation	[9]
Inherited retinal dystrophy	DISGGL77	Limited	Genetic Variation	[10]
Leber congenital amaurosis	DISMGH8F	Limited	CausalMutation	[10]

4 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 Cadherin-related family member 1 (CDHR1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Cadherin-related family member 1 (CDHR1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cadherin-related family member 1 (CDHR1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cadherin-related family member 1 (CDHR1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cadherin-related family member 1 (CDHR1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cadherin-related family member 1 (CDHR1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cadherin-related family member 1 (CDHR1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cadherin-related family member 1 (CDHR1).	[17]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. J Clin Invest. 2008 Aug;118(8):2908-16. doi: 10.1172/JCI35891.
• [3] Identification of genes associated with the corticotroph phenotype in bronchial carcinoid tumors.J Clin Endocrinol Metab. 2002 Nov;87(11):5015-22. doi: 10.1210/jc.2002-020598.
• [4] CDHR1 mutations in retinal dystrophies.Sci Rep. 2017 Aug 1;7(1):6992. doi: 10.1038/s41598-017-07117-8.
• [5] A Specific Macula-Predominant Retinal Phenotype Is Associated With the CDHR1 Variant c.783G>A, a Silent Mutation Leading to In-Frame Exon Skipping.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3388-3397. doi: 10.1167/iovs.18-26415.
• [6] Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy. J Med Genet. 2010 Oct;47(10):665-9. doi: 10.1136/jmg.2009.069120. Epub 2010 Aug 30.
• [7] Biallelic mutation of protocadherin-21 (PCDH21) causes retinal degeneration in humans. Mol Vis. 2010 Jan 15;16:46-52.
• [8] Identification of a novel mutation in the CDHR1 gene in a family with recessive retinal degeneration.Arch Ophthalmol. 2012 Oct;130(10):1301-8. doi: 10.1001/archophthalmol.2012.1906.
• [9] Characteristic Ocular Features in Cases of Autosomal Recessive PROM1 Cone-Rod Dystrophy.Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2347-2356. doi: 10.1167/iovs.19-26993.
• [10] Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
• [11] 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.
• [12] 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.
• [13] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [14] 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.
• [15] 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.
• [16] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.