Details of Drug Off-Target (DOT)

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

• DOT Name: Lysophospholipid acyltransferase 7 (MBOAT7)
• Synonyms: LPLAT 7; EC 2.3.1.-; 1-acylglycerophosphatidylinositol O-acyltransferase; Bladder and breast carcinoma-overexpressed gene 1 protein; Leukocyte receptor cluster member 4; Lysophosphatidylinositol acyltransferase; LPIAT; Lyso-PI acyltransferase; Membrane-bound O-acyltransferase domain-containing protein 7; O-acyltransferase domain-containing protein 7; h-mboa-7
• Gene Name: MBOAT7
• Related Disease:
  Alcoholic liver diseases
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Cardiovascular disease
  Chronic kidney disease
  Hepatitis
  Hepatocellular carcinoma
  Hydrocephalus
  Intellectual disability, autosomal recessive 57
  Liver cirrhosis
  Non-insulin dependent diabetes
  Adrenoleukodystrophy
  Alcoholic cirrhosis of liver
  Obesity
  Autosomal recessive non-syndromic intellectual disability
  Type-1/2 diabetes
  Gastric cancer
  Hepatitis B virus infection
  Intellectual disability
  Stomach cancer
• UniProt ID: MBOA7_HUMAN
• PDB ID: 8ERC
• EC Number: 2.3.1.-
• Pfam ID: PF03062
• Sequence:
  MSPEEWTYLVVLLISIPIGFLFKKAGPGLKRWGAAAVGLGLTLFTCGPHTLHSLVTILGT
  WALIQAQPCSCHALALAWTFSYLLFFRALSLLGLPTPTPFTNAVQLLLTLKLVSLASEVQ
  DLHLAQRKEMASGFSKGPTLGLLPDVPSLMETLSYSYCYVGIMTGPFFRYRTYLDWLEQP
  FPGAVPSLRPLLRRAWPAPLFGLLFLLSSHLFPLEAVREDAFYARPLPARLFYMIPVFFA
  FRMRFYVAWIAAECGCIAAGFGAYPVAAKARAGGGPTLQCPPPSSPEKAASLEYDYETIR
  NIDCYSTDFCVRVRDGMRYWNMTVQWWLAQYIYKSAPARSYVLRSAWTMLLSAYWHGLHP
  GYYLSFLTIPLCLAAEGRLESALRGRLSPGGQKAWDWVHWFLKMRAYDYMCMGFVLLSLA
  DTLRYWASIYFCIHFLALAALGLGLALGGGSPSRRKAASQPTSLAPEKLREE
• Function: Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle. Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell. In liver, participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation.
• Tissue Specificity: Overexpressed in metastatic breast and bladder carcinomas relative to normal breast epithelium and urothelium.
• KEGG Pathway: Glycerophospholipid metabolism (hsa00564)
• Reactome Pathway: Acyl chain remodelling of PI (R-HSA-1482922)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcoholic liver diseases	DISXEPHQ	Strong	Genetic Variation	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Chronic kidney disease	DISW82R7	Strong	Genetic Variation	[4]
Hepatitis	DISXXX35	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[7]
Intellectual disability, autosomal recessive 57	DISTGWA9	Strong	Autosomal recessive	[8]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[9]
Adrenoleukodystrophy	DISTUD1F	moderate	Genetic Variation	[10]
Alcoholic cirrhosis of liver	DISQ1WRT	moderate	Genetic Variation	[11]
Obesity	DIS47Y1K	moderate	Genetic Variation	[12]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[13]
Type-1/2 diabetes	DISIUHAP	Disputed	Genetic Variation	[14]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[15]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[16]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[17]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[15]

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 Lysophospholipid acyltransferase 7 (MBOAT7).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Lysophospholipid acyltransferase 7 (MBOAT7).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Lysophospholipid acyltransferase 7 (MBOAT7).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysophospholipid acyltransferase 7 (MBOAT7).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysophospholipid acyltransferase 7 (MBOAT7).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Lysophospholipid acyltransferase 7 (MBOAT7).	[21]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Lysophospholipid acyltransferase 7 (MBOAT7).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Lysophospholipid acyltransferase 7 (MBOAT7).	[23]

References

• [1] The rs626283 Variant in the MBOAT7 Gene is Associated with Insulin Resistance and Fatty Liver in Caucasian Obese Youth.Am J Gastroenterol. 2018 Mar;113(3):376-383. doi: 10.1038/ajg.2018.1. Epub 2018 Feb 27.
• [2] Expanding the phenotypic spectrum of MBOAT7-related intellectual disability.Am J Med Genet B Neuropsychiatr Genet. 2019 Oct;180(7):483-487. doi: 10.1002/ajmg.b.32749. Epub 2019 Jul 8.
• [3] Metabolic syndrome but not genetic polymorphisms known to induce NAFLD predicts increased total mortality in subjects with NAFLD (OPERA study).Scand J Clin Lab Invest. 2020 Feb-Apr;80(2):106-113. doi: 10.1080/00365513.2019.1700428. Epub 2019 Dec 18.
• [4] Association Between a Polymorphism in MBOAT7 and Chronic Kidney Disease in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease.Clin Gastroenterol Hepatol. 2020 Nov;18(12):2837-2839.e2. doi: 10.1016/j.cgh.2019.09.017. Epub 2019 Sep 20.
• [5] Lysophosphatidylinositol-acyltransferase-1 is involved in cytosolic Ca(2+) oscillations in macrophages.Genes Cells. 2019 May;24(5):366-376. doi: 10.1111/gtc.12681. Epub 2019 Apr 16.
• [6] Independent and additive effects of PNPLA3 and TM6SF2 polymorphisms on the development of non-B, non-C hepatocellular carcinoma.J Gastroenterol. 2019 May;54(5):427-436. doi: 10.1007/s00535-018-01533-x. Epub 2018 Nov 30.
• [7] Congenital hydrocephalus in genetically engineered mice.Vet Pathol. 2012 Jan;49(1):166-81. doi: 10.1177/0300985811415708. Epub 2011 Jul 11.
• [8] 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.
• [9] Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis.Am J Gastroenterol. 2018 Oct;113(10):1475-1483. doi: 10.1038/s41395-018-0041-8. Epub 2018 Mar 13.
• [10] Single-nucleotide rs738409 polymorphisms in the PNPLA3 gene are strongly associated with alcoholic liver disease in Han Chinese males.Hepatol Int. 2018 Sep;12(5):429-437. doi: 10.1007/s12072-018-9889-3. Epub 2018 Aug 21.
• [11] MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C.Nat Commun. 2016 Sep 15;7:12757. doi: 10.1038/ncomms12757.
• [12] Nonalcoholic Fatty Liver Disease (NAFLD), But not Its Susceptibility Gene Variants, Influences the Decrease of Kidney Function in Overweight/Obese Children.Int J Mol Sci. 2019 Sep 9;20(18):4444. doi: 10.3390/ijms20184444.
• [13] Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features. Am J Hum Genet. 2016 Oct 6;99(4):912-916. doi: 10.1016/j.ajhg.2016.07.019. Epub 2016 Sep 8.
• [14] Could inherited predisposition drive non-obese fatty liver disease? Results from German tertiary referral centers.J Hum Genet. 2018 May;63(5):621-626. doi: 10.1038/s10038-018-0420-4. Epub 2018 Feb 26.
• [15] Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level.Cancer Med. 2018 Oct;7(10):5057-5065. doi: 10.1002/cam4.1719. Epub 2018 Sep 6.
• [16] Effect of MBOAT7 variant on hepatitis B and C infections in Moroccan patients.Sci Rep. 2018 Aug 16;8(1):12247. doi: 10.1038/s41598-018-30824-9.
• [17] MBOAT7 is anchored to endomembranes by six transmembrane domains.J Struct Biol. 2019 Jun 1;206(3):349-360. doi: 10.1016/j.jsb.2019.04.006. Epub 2019 Apr 5.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] 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.
• [25] 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.