Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8C14QA)

DOT Name DnaJ homolog subfamily C member 21 (DNAJC21)
Synonyms DnaJ homolog subfamily A member 5; Protein GS3
Gene Name DNAJC21
Related Disease
Advanced cancer ( )
Bone marrow failure syndrome 3 ( )
Dyskeratosis congenita ( )
Griscelli syndrome ( )
Pancytopenia ( )
Shwachman-Diamond syndrome ( )
UniProt ID
DJC21_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00226 ; PF12171
Sequence
MKCHYEALGVRRDASEEELKKAYRKLALKWHPDKNLDNAAEAAEQFKLIQAAYDVLSDPQ
ERAWYDNHREALLKGGFDGEYQDDSLDLLRYFTVTCYSGYGDDEKGFYTVYRNVFEMIAK
EELESVLEEEVDDFPTFGDSQSDYDTVVHPFYAYWQSFCTQKNFAWKEEYDTRQASNRWE
KRAMEKENKKIRDKARKEKNELVRQLVAFIRKRDKRVQAHRKLVEEQNAEKARKAEEMRR
QQKLKQAKLVEQYREQSWMTMANLEKELQEMEARYEKEFGDGSDENEMEEHELKDEEDGK
DSDEAEDAELYDDLYCPACDKSFKTEKAMKNHEKSKKHREMVALLKQQLEEEEENFSRPQ
IDENPLDDNSEEEMEDAPKQKLSKKQKKKKQKPAQNYDDNFNVNGPGEGVKVDPEDTNLN
QDSAKELEDSPQENVSVTEIIKPCDDPKSEAKSVPKPKGKKTKDMKKPVRVPAEPQTMSV
LISCTTCHSEFPSRNKLFDHLKATGHARAPSSSSLNSATSSQSKKEKRKNR
Function May act as a co-chaperone for HSP70. May play a role in ribosomal RNA (rRNA) biogenesis, possibly in the maturation of the 60S subunit. Binds the precursor 45S rRNA.
Tissue Specificity Expressed in brain, placenta, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Bone marrow failure syndrome 3 DISVQKA4 Strong Autosomal recessive [1]
Dyskeratosis congenita DISSXV0K Strong Biomarker [2]
Griscelli syndrome DISTHCOQ Strong Genetic Variation [3]
Pancytopenia DISVKEHV Strong Biomarker [2]
Shwachman-Diamond syndrome DISW57NW Supportive Autosomal recessive [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [5]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [6]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [8]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [8]
Nefazodone DM4ZS8M Approved Nefazodone decreases the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [9]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [10]
APR-246 DMNFADH Phase 2 APR-246 affects the expression of DnaJ homolog subfamily C member 21 (DNAJC21). [11]
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⏷ Show the Full List of 7 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of DnaJ homolog subfamily C member 21 (DNAJC21). [7]
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References

1 DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation. Am J Hum Genet. 2016 Jul 7;99(1):115-24. doi: 10.1016/j.ajhg.2016.05.002. Epub 2016 Jun 23.
2 Refining the phenotype associated with biallelic DNAJC21 mutations.Clin Genet. 2018 Aug;94(2):252-258. doi: 10.1111/cge.13370. Epub 2018 Jun 7.
3 Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure.Braz J Med Biol Res. 2008 Oct;41(10):839-48. doi: 10.1590/s0100-879x2008001000002.
4 Biallelic mutations in DNAJC21 cause Shwachman-Diamond syndrome. Blood. 2017 Mar 16;129(11):1557-1562. doi: 10.1182/blood-2016-08-735431. Epub 2017 Jan 6.
5 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
7 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.
8 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
9 Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
10 The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
11 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.