Details of Drug Off-Target (DOT)

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

• DOT Name: Protein HID1 (HID1)
• Synonyms: Down-regulated in multiple cancers 1; HID1 domain-containing protein; Protein hid-1 homolog
• Gene Name: HID1
• Related Disease:
  Advanced cancer
  Developmental and epileptic encephalopathy 105 with hypopituitarism
  Gastric ulcer
  Obesity
• UniProt ID: HID1_HUMAN
• Pfam ID: PF12722
• Sequence:
  MGSTDSKLNFRKAVIQLTTKTQPVEATDDAFWDQFWADTATSVQDVFALVPAAEIRAVRE
  ESPSNLATLCYKAVEKLVQGAESGCHSEKEKQIVLNCSRLLTRVLPYIFEDPDWRGFFWS
  TVPGAGRGGQGEEDDEHARPLAESLLLAIADLLFCPDFTVQSHRRSTVDSAEDVHSLDSC
  EYIWEAGVGFAHSPQPNYIHDMNRMELLKLLLTCFSEAMYLPPAPESGSTNPWVQFFCST
  ENRHALPLFTSLLNTVCAYDPVGYGIPYNHLLFSDYREPLVEEAAQVLIVTLDHDSASSA
  SPTVDGTTTGTAMDDADPPGPENLFVNYLSRIHREEDFQFILKGIARLLSNPLLQTYLPN
  STKKIQFHQELLVLFWKLCDFNKKFLFFVLKSSDVLDILVPILFFLNDARADQSRVGLMH
  IGVFILLLLSGERNFGVRLNKPYSIRVPMDIPVFTGTHADLLIVVFHKIITSGHQRLQPL
  FDCLLTIVVNVSPYLKSLSMVTANKLLHLLEAFSTTWFLFSAAQNHHLVFFLLEVFNNII
  QYQFDGNSNLVYAIIRKRSIFHQLANLPTDPPTIHKALQRRRRTPEPLSRTGSQEGTSME
  GSRPAAPAEPGTLKTSLVATPGIDKLTEKSQVSEDGTLRSLEPEPQQSLEDGSPAKGEPS
  QAWREQRRPSTSSASGQWSPTPEWVLSWKSKLPLQTIMRLLQVLVPQVEKICIDKGLTDE
  SEILRFLQHGTLVGLLPVPHPILIRKYQANSGTAMWFRTYMWGVIYLRNVDPPVWYDTDV
  KLFEIQRV
• Function: May play an important role in the development of cancers in a broad range of tissues.
• Tissue Specificity: Expressed in heart, skeletal muscle, colon, spleen, kidney, liver, small intestine and lung. Highest expression is seen in brain and placenta. Loss of expression is seen in some breast, cervical, hepatocellular, lung, thyroid, gastric and renal cell-cancer lines. Highly expressed in secretory cell lines. Expressed in almost all regions of the brain, in cerebellum, anterior frontal cortex, and striatum.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Developmental and epileptic encephalopathy 105 with hypopituitarism	DISUYF1P	Strong	Autosomal recessive	[2]
Gastric ulcer	DISBBGVO	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Altered Expression	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Protein HID1 (HID1) affects the response to substance of NAPQI.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein HID1 (HID1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein HID1 (HID1).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein HID1 (HID1).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein HID1 (HID1).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein HID1 (HID1).	[10]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein HID1 (HID1).	[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 affects the methylation of Protein HID1 (HID1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein HID1 (HID1).	[11]

References

• [1] Identification of DMC1, a novel gene in the TOC region on 17q25.1 that shows loss of expression in multiple human cancers.J Hum Genet. 2001;46(2):90-5. doi: 10.1007/s100380170115.
• [2] The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet. 2017 Aug;136(8):921-939. doi: 10.1007/s00439-017-1821-8. Epub 2017 Jun 9.
• [3] Gastroprotective potential of methanolic extract and dimethyl cardamonin from Campomanesia reitziana fruits in mice.Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):661-666. doi: 10.1007/s00210-017-1369-0. Epub 2017 Apr 1.
• [4] Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.Int J Obes (Lond). 2016 Dec;40(12):1832-1840. doi: 10.1038/ijo.2016.127. Epub 2016 Jul 27.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [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] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [13] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.