Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT793RNP)

• DOT Name: Hippocalcin-like protein 4 (HPCAL4)
• Synonyms: HLP4
• Gene Name: HPCAL4
• UniProt ID: HPCL4_HUMAN
• Pfam ID: PF00036 ; PF13499
• Sequence:
  MGKTNSKLAPEVLEDLVQNTEFSEQELKQWYKGFLKDCPSGILNLEEFQQLYIKFFPYGD
  ASKFAQHAFRTFDKNGDGTIDFREFICALSVTSRGSFEQKLNWAFEMYDLDGDGRITRLE
  MLEIIEAIYKMVGTVIMMRMNQDGLTPQQRVDKIFKKMDQDKDDQITLEEFKEAAKSDPS
  IVLLLQCDMQK
• Function: May be involved in the calcium-dependent regulation of rhodopsin phosphorylation.

Molecular Interaction Atlas (MIA) of This DOT

10 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 Hippocalcin-like protein 4 (HPCAL4).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Hippocalcin-like protein 4 (HPCAL4).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hippocalcin-like protein 4 (HPCAL4).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Hippocalcin-like protein 4 (HPCAL4).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Hippocalcin-like protein 4 (HPCAL4).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Hippocalcin-like protein 4 (HPCAL4).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Hippocalcin-like protein 4 (HPCAL4).	[7]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Hippocalcin-like protein 4 (HPCAL4).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Hippocalcin-like protein 4 (HPCAL4).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Hippocalcin-like protein 4 (HPCAL4).	[12]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hippocalcin-like protein 4 (HPCAL4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Hippocalcin-like protein 4 (HPCAL4).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] 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.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [8] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] 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.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.