Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT74OZ2Z)

• DOT Name: Mas-related G-protein coupled receptor member F (MRGPRF)
• Synonyms: Mas-related gene F protein; G-protein coupled receptor 140; G-protein coupled receptor 168
• Gene Name: MRGPRF
• Related Disease:
  Nephrocalcinosis
  Autoimmune haemolytic anaemia
  Burkitt lymphoma
  Congestive heart failure
  Distal renal tubular acidosis
  Kaposi sarcoma
  Osteopetrosis
  Proximal renal tubular acidosis
  Renal tubular acidosis
  Tuberculosis
  Alcohol dependence
  Carcinoma of liver and intrahepatic biliary tract
  Chronic kidney disease
  Liver cancer
  Acute myelogenous leukaemia
  Asthma
  leukaemia
  Leukemia
  Advanced cancer
  Intellectual disability
  Nasopharyngeal carcinoma
• UniProt ID: MRGRF_HUMAN
• Pfam ID: PF00001
• Sequence:
  MAGNCSWEAHPGNRNKMCPGLSEAPELYSRGFLTIEQIAMLPPPAVMNYIFLLLCLCGLV
  GNGLVLWFFGFSIKRNPFSIYFLHLASADVGYLFSKAVFSILNTGGFLGTFADYIRSVCR
  VLGLCMFLTGVSLLPAVSAERCASVIFPAWYWRRRPKRLSAVVCALLWVLSLLVTCLHNY
  FCVFLGRGAPGAACRHMDIFLGILLFLLCCPLMVLPCLALILHVECRARRRQRSAKLNHV
  ILAMVSVFLVSSIYLGIDWFLFWVFQIPAPFPEYVTDLCICINSSAKPIVYFLAGRDKSQ
  RLWEPLRVVFQRALRDGAELGEAGGSTPNTVTMEMQCPPGNAS
• Function: Orphan receptor. May bind to a neuropeptide and may regulate nociceptor function and/or development, including the sensation or modulation of pain.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephrocalcinosis	DIS5ZVJP	Definitive	Biomarker	[1]
Autoimmune haemolytic anaemia	DIS7MS3M	Strong	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Distal renal tubular acidosis	DISP6CYE	Strong	Genetic Variation	[5]
Kaposi sarcoma	DISC1H1Z	Strong	Genetic Variation	[6]
Osteopetrosis	DIS7GHNM	Strong	Biomarker	[7]
Proximal renal tubular acidosis	DIS8M3CV	Strong	Biomarker	[5]
Renal tubular acidosis	DISE1NDR	Strong	Altered Expression	[8]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[4]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[9]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[10]
Chronic kidney disease	DISW82R7	moderate	Biomarker	[1]
Liver cancer	DISDE4BI	moderate	Biomarker	[10]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Biomarker	[11]
Asthma	DISW9QNS	Disputed	Biomarker	[12]
leukaemia	DISS7D1V	Disputed	Biomarker	[11]
Leukemia	DISNAKFL	Disputed	Biomarker	[11]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[13]
Intellectual disability	DISMBNXP	Limited	Biomarker	[14]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[13]

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 Mas-related G-protein coupled receptor member F (MRGPRF).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mas-related G-protein coupled receptor member F (MRGPRF).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mas-related G-protein coupled receptor member F (MRGPRF).	[21]

References

• [1] A novel SLC4A1 variant in an autosomal dominant distal renal tubular acidosis family with a severe phenotype.Endocrine. 2010 Jun;37(3):473-8. doi: 10.1007/s12020-010-9340-6. Epub 2010 Apr 17.
• [2] AN UNUSUAL CASE OF FAMILIAL SYSTEMIC LUPUS ERYTHEMATOSUS WITH DISTAL RENAL TUBULAR ACIDOSIS AND HEMOLYTIC ANEMIA.Iran J Kidney Dis. 2019 Sep;13(5):337-339.
• [3] IRF4 promotes Epstein-Barr virus activation in Burkitt's lymphoma cells.J Gen Virol. 2019 May;100(5):851-862. doi: 10.1099/jgv.0.001249. Epub 2019 Mar 25.
• [4] Paediatric deaths in a tertiary government hospital setting, Malawi.Paediatr Int Child Health. 2019 Nov;39(4):240-248. doi: 10.1080/20469047.2018.1536873. Epub 2018 Nov 19.
• [5] Hereditary renal tubular disorders in Turkey: demographic, clinical, and laboratory features.Clin Exp Nephrol. 2011 Feb;15(1):108-13. doi: 10.1007/s10157-010-0367-z. Epub 2010 Nov 20.
• [6] Two microPeptides are translated from a KSHV polycistronic RNA in human cells by leaky scanning mechanism.Biochem Biophys Res Commun. 2020 Feb 12;522(3):568-573. doi: 10.1016/j.bbrc.2019.11.087. Epub 2019 Nov 27.
• [7] Familial pure proximal renal tubular acidosis--a clinical and genetic study.Nephrol Dial Transplant. 2008 Apr;23(4):1211-5. doi: 10.1093/ndt/gfm583. Epub 2007 Sep 19.
• [8] Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection.J Virol. 2006 Jun;80(11):5371-82. doi: 10.1128/JVI.02299-05.
• [9] Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study.Adicciones. 2018 Jan 12;30(4):292-300. doi: 10.20882/adicciones.931.
• [10] Growth inhibition of hepatocellular carcinoma cells in vitro and in vivo by the 8-methoxy analog of WMC79.Cancer Chemother Pharmacol. 2009 Apr;63(5):769-78. doi: 10.1007/s00280-008-0801-z. Epub 2008 Jul 19.
• [11] Role of peroxisome proliferator-activated receptor-gamma and its coactivator DRIP205 in cellular responses to CDDO (RTA-401) in acute myelogenous leukemia.Cancer Res. 2010 Jun 15;70(12):4949-60. doi: 10.1158/0008-5472.CAN-09-1962. Epub 2010 May 25.
• [12] Nrf2 Activator RTA-408 Protects Against Ozone-Induced Acute Asthma Exacerbation by Suppressing ROS and T17 Cells.Inflammation. 2019 Oct;42(5):1843-1856. doi: 10.1007/s10753-019-01046-6.
• [13] Rta-IgG as a biomarker for diagnosis and post treatment prognostic of nasopharyngeal carcinoma.Cancer Biomark. 2016;16(3):467-76. doi: 10.3233/CBM-160586.
• [14] Genetic diseases of acid-base transporters.Annu Rev Physiol. 2002;64:899-923. doi: 10.1146/annurev.physiol.64.092801.141759.
• [15] 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.
• [16] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [17] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] 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.
• [20] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [21] 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.
• [22] 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.