Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2MKQ5Z)

• DOT Name: WD repeat-containing protein 73
• Gene Name: WDR73
• Related Disease:
  Galloway-Mowat syndrome 1
  CAMOS syndrome
  Galloway-Mowat syndrome
• UniProt ID: WDR73_HUMAN
• Sequence:
  MDPGDDWLVESLRLYQDFYAFDLSGATRVLEWIDDKGVFVAGYESLKKNEILHLKLPLRL
  SVKENKGLFPERDFKVRHGGFSDRSIFDLKHVPHTRLLVTSGLPGCYLQVWQVAEDSDVI
  KAVSTIAVHEKEESLWPRVAVFSTLAPGVLHGARLRSLQVVDLESRKTTYTSDVSDSEEL
  SSLQVLDADTFAFCCASGRLGLVDTRQKWAPLENRSPGPGSGGERWCAEVGSWGQGPGPS
  IASLGSDGRLCLLDPRDLCHPVSSVQCPVSVPSPDPELLRVTWAPGLKNCLAISGFDGTV
  QVYDATSWDGTRSQDGTRSQVEPLFTHRGHIFLDGNGMDPAPLVTTHTWHPCRPRTLLSA
  TNDASLHVWDWVDLCAPR
• Function: May play a role in the regulation of microtubule organization and dynamics.
• Tissue Specificity: Expressed in kidney and brain. In the kidney, expressed in glomeruli, most probably in podocytes, and in tubules (at protein level). In the brain, expressed in the cerebellum, with high levels in Purkinje cells and their projecting axons, in the deep cerebellar nuclei and in pyramidal neurons of the cerebral cortex (at protein level). In the white matter, mainly present in astrocytes, but not in oligodendrocytes (at protein level). Also highly expressed in endothelial cells of cerebral capillaries (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Galloway-Mowat syndrome 1	DIS7B3HB	Strong	Autosomal recessive	[1]
CAMOS syndrome	DISSHNG7	Supportive	Autosomal recessive	[2]
Galloway-Mowat syndrome	DISVB7IM	Supportive	Autosomal recessive	[3]

6 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 WD repeat-containing protein 73.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of WD repeat-containing protein 73.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of WD repeat-containing protein 73.	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of WD repeat-containing protein 73.	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of WD repeat-containing protein 73.	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of WD repeat-containing protein 73.	[9]

References

• [1] PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect. J Biol Chem. 1975 Mar 25;250(6):2227-31.
• [2] WDR73 Mutations Cause Infantile Neurodegeneration and Variable Glomerular Kidney Disease. Hum Mutat. 2015 Nov;36(11):1021-8. doi: 10.1002/humu.22828. Epub 2015 Aug 6.
• [3] Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome. Am J Hum Genet. 2014 Dec 4;95(6):637-48. doi: 10.1016/j.ajhg.2014.10.011. Epub 2014 Nov 13.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.