Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6LHJY)

• DOT Name: LHFPL tetraspan subfamily member 6 protein (LHFPL6)
• Synonyms: Lipoma HMGIC fusion partner
• Gene Name: LHFPL6
• Related Disease:
  Advanced cancer
  Chromosomal disorder
  Depression
  Gliosarcoma
  Hamartoma
  Neoplasm
  Neovascular age-related macular degeneration
  Psoriasis
  Hereditary breast carcinoma
• UniProt ID: LHPL6_HUMAN
• Pfam ID: PF10242
• Sequence:
  MASSLTCTGVIWALLSFLCAATSCVGFFMPYWLWGSQLGKPVSFGTFRRCSYPVHDESRQ
  MMVMVEECGRYASFQGIPSAEWRICTIVTGLGCGLLLLVALTALMGCCVSDLISRTVGRV
  AGGIQFLGGLLIGAGCALYPLGWDSEEVRQTCGYTSGQFDLGKCEIGWAYYCTGAGATAA
  MLLCTWLACFSGKKQKHYPY
• Tissue Specificity: Pancreas, kidney, skeletal muscle, liver, lung brain, heart, colon, small intestine, uterus, testis, prostate, thymus, spleen and placenta.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[3]
Gliosarcoma	DIS985MG	Strong	Biomarker	[4]
Hamartoma	DIS0I87H	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[5]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[6]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[7]
Hereditary breast carcinoma	DISAEZT5	Limited	Biomarker	[8]

21 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 LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[18]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[20]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[22]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[26]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of LHFPL tetraspan subfamily member 6 protein (LHFPL6).	[27]

References

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• [5] Absence of HMGIC-LHFP fusion in pulmonary chondroid hamartomas with aberrations involving chromosomal regions 12q13 through 15 and 13q12 through q14.Cancer Genet Cytogenet. 2002 Feb;133(1):90-3. doi: 10.1016/s0165-4608(01)00553-2.
• [6] A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.Sci Rep. 2017 Aug 3;7(1):7173. doi: 10.1038/s41598-017-07526-9.
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• [8] Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors.Int J Cancer. 2003 Feb 20;103(5):616-23. doi: 10.1002/ijc.10864.
• [9] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
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• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [13] 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.
• [14] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [15] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
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• [17] 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.
• [18] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [19] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [20] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [21] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [22] 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.
• [23] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [24] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [25] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [26] 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.
• [27] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.