Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3GMU2X)

• DOT Name: HHIP-like protein 1 (HHIPL1)
• Gene Name: HHIPL1
• Related Disease:
  Adenoma
  Cardiovascular disease
  Coronary atherosclerosis
  Coronary heart disease
  Myocardial infarction
  Arteriosclerosis
  Atherosclerosis
• UniProt ID: HIPL1_HUMAN
• Pfam ID: PF03024 ; PF07995 ; PF00530
• Sequence:
  MARARAGALLALWVLGAAAHPQCLDFRPPFRPTQPLRLCAQYSDFGCCDEGRDAELTRRF
  WALASRVDAAEWAACAGYARDLLCQECSPYAAHLYDAEDPFTPLRTVPGLCQDYCLDMWH
  KCRGLFRHLSTDQELWALEGNLARFCRYLSLDDTDYCFPYLLVNKNLNSNLGHVVADAKG
  CLQLCLEEVANGLRNPVAMVHARDGTHRFFVAEQVGLVWAYLPDRSRLGKPFLNISRVVL
  TSPWEGDERGFLGIAFHPSFQHNRRLYVYYSVGIRSSEWIRISEFRVSEDDENAVDHSSE
  RIILEVKEPASNHNGGQLLFGDDGYLYIFTGDGGMAGDPFGTFGNAQNKSALLGKVLRID
  VDRKERGLPYGIPPDNPFVGDPAAQPEVYALGVRNMWRCSFDRGDPSSGTGRGRLFCGDV
  GQNKFEEVDVVERGGNYGWRAREGFECYDRSLCANTSLNDLLPIFAYPHTVGKSVTGGYV
  YRGCEYPNLNGLYIFGDFMSGRLMSLQENPGTGQWQYSEICMGHGQTCEFPGLINNYYPY
  IISFGEDEAGELYFMSTGEPSATAPRGVVYKIIDASRRAPPGKCQIQPAQVKIRSRLIPF
  VPKEKFIPKTRSTPRPTARAPTRAPRRGRPTAAPPAPTPRPARPTQQPGSRRGGGRRRGR
  LNSASRAFRDGEVRLVRPAGLSSGSGRVEVFVGGRWGTVCDDSWNISGAAVVCRQLGFAY
  AVRAVKRAEFGQGGSLPILLDDVRCAGWERNLLECQHNGVGTHNCEHDEDAGVVCSHQNP
  DL

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[3]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[2]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[3]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of HHIP-like protein 1 (HHIPL1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of HHIP-like protein 1 (HHIPL1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of HHIP-like protein 1 (HHIPL1).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of HHIP-like protein 1 (HHIPL1).	[6]

References

• [1] Quantitative, genome-wide analysis of the DNA methylome in sporadic pituitary adenomas.Endocr Relat Cancer. 2012 Nov 19;19(6):805-16. doi: 10.1530/ERC-12-0251. Print 2012 Dec.
• [2] HHIPL-1 (rs2895811) gene polymorphism is associated with cardiovascular risk factors and cardiometabolic parameters in Mexicans patients with myocardial infarction.Gene. 2018 Jul 15;663:34-40. doi: 10.1016/j.gene.2018.04.030. Epub 2018 Apr 12.
• [3] HHIPL1, a Gene at the 14q32 Coronary Artery Disease Locus, Positively Regulates Hedgehog Signaling and Promotes Atherosclerosis.Circulation. 2019 Aug 6;140(6):500-513. doi: 10.1161/CIRCULATIONAHA.119.041059. Epub 2019 Jun 5.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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.
• [7] 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.