Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOL14ZD)

• DOT Name: Lipase maturation factor 1 (LMF1)
• Synonyms: Transmembrane protein 112
• Gene Name: LMF1
• Related Disease:
  Central nervous system neoplasm
  Familial lipoprotein lipase deficiency
  Glioma
  Lipase deficiency, combined
  Lipodystrophy
  Norum disease
  Pancreatitis
• UniProt ID: LMF1_HUMAN
• Pfam ID: PF06762
• Sequence:
  MRPDSPTMAAPAESLRRRKTGYSDPEPESPPAPGRGPAGSPAHLHTGTFWLTRIVLLKAL
  AFVYFVAFLVAFHQNKQLIGDRGLLPCRVFLKNFQQYFQDRTSWEVFSYMPTILWLMDWS
  DMNSNLDLLALLGLGISSFVLITGCANMLLMAALWGLYMSLVNVGHVWYSFGWESQLLET
  GFLGIFLCPLWTLSRLPQHTPTSRIVLWGFRWLIFRIMLGAGLIKIRGDRCWRDLTCMDF
  HYETQPMPNPVAYYLHHSPWWFHRFETLSNHFIELLVPFFLFLGRRACIIHGVLQILFQA
  VLIVSGNLSFLNWLTMVPSLACFDDATLGFLFPSGPGSLKDRVLQMQRDIRGARPEPRFG
  SVVRRAANVSLGVLLAWLSVPVVLNLLSSRQVMNTHFNSLHIVNTYGAFGSITKERAEVI
  LQGTASSNASAPDAMWEDYEFKCKPGDPSRRPCLISPYHYRLDWLMWFAAFQTYEHNDWI
  IHLAGKLLASDAEALSLLAHNPFAGRPPPRWVRGEHYRYKFSRPGGRHAAEGKWWVRKRI
  GAYFPPLSLEELRPYFRDRGWPLPGPL
• Function: Involved in the maturation of specific proteins in the endoplasmic reticulum. Required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway. Each LMF1 molecule chaperones 50 or more molecules of LPL.
• Reactome Pathway: Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[1]
Familial lipoprotein lipase deficiency	DIS0M7NJ	Strong	Genetic Variation	[2]
Glioma	DIS5RPEH	Strong	Genetic Variation	[1]
Lipase deficiency, combined	DISWMWIH	Strong	Autosomal recessive	[3]
Lipodystrophy	DIS3SGVD	Strong	Biomarker	[4]
Norum disease	DISSJE3M	Limited	Biomarker	[5]
Pancreatitis	DIS0IJEF	Limited	Biomarker	[6]

3 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 Lipase maturation factor 1 (LMF1).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Lipase maturation factor 1 (LMF1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipase maturation factor 1 (LMF1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lipase maturation factor 1 (LMF1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Lipase maturation factor 1 (LMF1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Lipase maturation factor 1 (LMF1).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Lipase maturation factor 1 (LMF1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lipase maturation factor 1 (LMF1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lipase maturation factor 1 (LMF1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lipase maturation factor 1 (LMF1).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Lipase maturation factor 1 (LMF1).	[16]

References

• [1] Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.Nat Genet. 2017 May;49(5):789-794. doi: 10.1038/ng.3823. Epub 2017 Mar 27.
• [2] New rare genetic variants of LMF1 gene identified in severe hypertriglyceridemia.J Clin Lipidol. 2018 Sep-Oct;12(5):1244-1252. doi: 10.1016/j.jacl.2018.06.018. Epub 2018 Jul 7.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Inherited lipodystrophies and hypertriglyceridemia.Curr Opin Lipidol. 2009 Aug;20(4):300-8. doi: 10.1097/MOL.0b013e32832d4a33.
• [5] A complex phenotype in a child with familial HDL deficiency due to a novel frameshift mutation in APOA1 gene (apoA-IGuastalla).J Clin Lipidol. 2015 Nov-Dec;9(6):837-846. doi: 10.1016/j.jacl.2015.09.001. Epub 2015 Sep 18.
• [6] Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis.PLoS One. 2015 Jun 16;10(6):e0129488. doi: 10.1371/journal.pone.0129488. eCollection 2015.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] 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.
• [13] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [14] 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.
• [15] 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.
• [16] 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.