Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO4WCU9)

• DOT Name: Calreticulin-3 (CALR3)
• Synonyms: Calreticulin-2; Calsperin
• Gene Name: CALR3
• Related Disease:
  Cataract
  Vitiligo
  Hypertrophic cardiomyopathy
  Cardiomyopathy
• UniProt ID: CALR3_HUMAN
• Pfam ID: PF00262
• Sequence:
  MARALVQLWAICMLRVALATVYFQEEFLDGEHWRNRWLQSTNDSRFGHFRLSSGKFYGHK
  EKDKGLQTTQNGRFYAISARFKPFSNKGKTLVIQYTVKHEQKMDCGGGYIKVFPADIDQK
  NLNGKSQYYIMFGPDICGFDIKKVHVILHFKNKYHENKKLIRCKVDGFTHLYTLILRPDL
  SYDVKIDGQSIESGSIEYDWNLTSLKKETSPAESKDWEQTKDNKAQDWEKHFLDASTSKQ
  SDWNGDLDGDWPAPMLQKPPYQDGLKPEGIHKDVWLHRKMKNTDYLTQYDLSEFENIGAI
  GLELWQVRSGTIFDNFLITDDEEYADNFGKATWGETKGPEREMDAIQAKEEMKKAREEEE
  EELLSGKINRHEHYFNQFHRRNEL
• Function: During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility. CALR3 capacity for calcium-binding may be absent or much lower than that of CALR.
• Tissue Specificity: Testis specific.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cataract	DISUD7SL	Strong	Biomarker	[1]
Vitiligo	DISR05SL	Strong	Biomarker	[2]
Hypertrophic cardiomyopathy	DISQG2AI	Disputed	Autosomal dominant	[3]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Calreticulin-3 (CALR3).	[5]

References

• [1] The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter. Hum Mol Genet. 2013 Aug 15;22(16):3218-26.
• [2] Role of Optical Coherence Tomography in the Prognosis of Vogt-Koyanagi-Harada Disease.Ocul Immunol Inflamm. 2021 Jan 2;29(1):118-123. doi: 10.1080/09273948.2019.1655580. Epub 2019 Oct 2.
• [3] 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.
• [4] Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy.Eur J Hum Genet. 2018 Nov;26(11):1603-1610. doi: 10.1038/s41431-018-0208-1. Epub 2018 Jul 9.
• [5] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.