Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGPG077)

• DOT Name: Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5)
• Synonyms: Cat eye syndrome critical region protein 5
• Gene Name: HDHD5
• UniProt ID: HDHD5_HUMAN
• Pfam ID: PF13344
• Sequence:
  MAAWGCVAALGAARGLCWRAARAAAGLQGRPARRCYAVGPAQSPPTFGFLLDIDGVLVRG
  HRVIPAALKAFRRLVNSQGQLRVPVVFVTNAGNILQHSKAQELSALLGCEVDADQVILSH
  SPMKLFSEYHEKRMLVSGQGPVMENAQGLGFRNVVTVDELRMAFPLLDMVDLERRLKTTP
  LPRNDFPRIEGVLLLGEPVRWETSLQLIMDVLLSNGSPGAGLATPPYPHLPVLASNMDLL
  WMAEAKMPRFGHGTFLLCLETIYQKVTGKELRYEGLMGKPSILTYQYAEDLIRRQAERRG
  WAAPIRKLYAVGDNPMSDVYGANLFHQYLQKATHDGAPELGAGGTRQQQPSASQSCISIL
  VCTGVYNPRNPQSTEPVLGGGEPPFHGHRDLCFSPGLMEASHVVNDVNEAVQLVFRKEGW
  ALE
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[7]

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 Haloacid dehalogenase-like hydrolase domain-containing 5 (HDHD5).	[5]

References

• [1] 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.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.