Details of Drug Off-Target (DOT)

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

• DOT Name: Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2)
• Synonyms: Dbs-related Rho family guanine nucleotide exchange factor; MCF2-transforming sequence-like protein 2
• Gene Name: MCF2L2
• Related Disease:
  Paroxysmal extreme pain disorder
  Abdominal aortic aneurysm
  Acute myelogenous leukaemia
  Bacterial endocarditis
  Bone cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Complex regional pain syndrome
  Depression
  Erythromelalgia
  Gastroesophageal reflux disease
  Iatrogenic disease
  Infective endocarditis
  Liver cirrhosis
  Nervous system inflammation
  Neuroblastoma
  Peripheral neuropathy
  Polycystic ovarian syndrome
  Primary erythermalgia
  Varicose veins
  Coronary atherosclerosis
  Myocardial ischemia
  Osteoarthritis
  Hyperglycemia
  Diabetic kidney disease
  Nephropathy
  Sciatica/lumbar radicular pain
  Type-1 diabetes
• UniProt ID: MF2L2_HUMAN
• Pfam ID: PF13716 ; PF00621
• Sequence:
  MLSCLKEEMPPQELTRRLATVITHVDEIMQQEVRPLMAVEIIEQLHRQFAILSGGRGEDG
  APIITFPEFSGFKHIPDEDFLNVMTYLTSIPSVEAASIGFIVVIDRRRDKWSSVKASLTR
  IAVAFPGNLQLIFILRPSRFIQRTFTDIGIKYYRNEFKTKVPIIMVNSVSDLHGYIDKSQ
  LTRELGGTLEYRHGQWVNHRTAIENFALTLKTTAQMLQTFGSCLATAELPRSMLSTEDLL
  MSHTRQRDKLQDELKLLGKQGTTLLSCIQEPATKCPNSKLNLNQLENVTTMERLLVQLDE
  TEKAFSHFWSEHHLKLNQCLQLQHFEHDFCKAKLALDNLLEEQAEFTGIGDSVMHVEQIL
  KEHKKLEEKSQEPLEKAQLLALVGDQLIQSHHYAADAIRPRCVELRHLCDDFINGNKKKW
  DILGKSLEFHRQLDKVSQWCEAGIYLLASQAVDKCQSREGVDIALNDIATFLGTVKEYPL
  LSPKEFYNEFELLLTLDAKAKAQKVLQRLDDVQEIFHKRQVSLMKLAAKQTRPVQPVAPH
  PESSPKWVSSKTSQPSTSVPLARPLRTSEEPYTETELNSRGKEDDETKFEVKSEEIFESH
  HERGNPELEQQARLGDLSPRRRIIRDLLETEEIYIKEIKSIIDGYITPMDFIWLKHLIPD
  VLQNNKDFLFGNIRELYEFHNRTFLKELEKCAENPELLAHCFLKRKEDLQIYFKYHKNLP
  RARAIWQECQDCAYFGVCQRQLDHNLPLFKYLKGPSQRLIKYQMLLKGLLDFESPEDMEI
  DPGELGGSAKDGPKRTKDSAFSTELQQALAVIEDLIKSCELAVDLAAVTECPDDIGKLGK
  LLLHGPFSVWTIHKDRYKMKDLIRFKPSQRQIYLFERGIVFCKIRMEPGDQGLSPHYSFK
  KTMKLMTLSIRQLGRGSHRKFEIASRNGLEKYILQAASKEIRDCWFSEISKLLMEQQNNI
  KDQGNPQFEMSTSKGSGAGSGPWIKNMERATTSKEDPASSTGGIKGCSSREFSSMDTFED
  CEGAEDMEKESSALSLAGLFQSDDSHETCSSKSAFLERGESSQGEKEERDEEETATRSTE
  EERAGASTGRLAPAGATAGFQARALRPRTSAQES
• Function: Probably functions as a guanine nucleotide exchange factor.
• Tissue Specificity: Significantly expressed in brain and modestly in pancreas, brain and testis.

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Paroxysmal extreme pain disorder	DISNHO6B	Definitive	Genetic Variation	[1]
Abdominal aortic aneurysm	DISD06OF	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Bacterial endocarditis	DIS920N0	Strong	Biomarker	[4]
Bone cancer	DIS38NA0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Complex regional pain syndrome	DIS625IE	Strong	Altered Expression	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Erythromelalgia	DIS1IW05	Strong	Genetic Variation	[9]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[10]
Iatrogenic disease	DISNZCYA	Strong	Biomarker	[11]
Infective endocarditis	DIS88NSA	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[12]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[13]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[14]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[13]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[15]
Primary erythermalgia	DISRR1LN	Strong	Genetic Variation	[16]
Varicose veins	DISIMBN2	Strong	Biomarker	[17]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[18]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[18]
Osteoarthritis	DIS05URM	moderate	Biomarker	[19]
Hyperglycemia	DIS0BZB5	Disputed	Biomarker	[20]
Diabetic kidney disease	DISJMWEY	Limited	Genetic Variation	[21]
Nephropathy	DISXWP4P	Limited	Genetic Variation	[21]
Sciatica/lumbar radicular pain	DIS01KTQ	Limited	Genetic Variation	[22]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[21]

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 Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[28]

4 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 Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable guanine nucleotide exchange factor MCF2L2 (MCF2L2).	[29]

References

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• [3] Novel Disease Risk Model for Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Cell Transplantation.Biol Blood Marrow Transplant. 2020 Jan;26(1):197-203. doi: 10.1016/j.bbmt.2019.09.006. Epub 2019 Sep 10.
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• [5] Transcriptional Regulation of Voltage-Gated Sodium Channels Contributes to GM-CSF-Induced Pain.J Neurosci. 2019 Jun 26;39(26):5222-5233. doi: 10.1523/JNEUROSCI.2204-18.2019. Epub 2019 Apr 23.
• [6] Should Breast Cancer Surgery Be Done in an Outpatient Setting?: Health Economics From the Perspective of Service Providers.Geburtshilfe Frauenheilkd. 2017 Aug;77(8):879-886. doi: 10.1055/s-0043-114427. Epub 2017 Aug 24.
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• [8] Dihydromyricetin affects BDNF levels in the nervous system in rats with comorbid diabetic neuropathic pain and depression.Sci Rep. 2019 Oct 10;9(1):14619. doi: 10.1038/s41598-019-51124-w.
• [9] Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7.Mol Pain. 2007 Jan 19;3:3. doi: 10.1186/1744-8069-3-3.
• [10] Cough reflex sensitivity does not correlate with the esophageal sensitivity to acid in patients with gastroesophageal reflux disease.Respir Physiol Neurobiol. 2018 Nov;257:25-29. doi: 10.1016/j.resp.2018.03.011. Epub 2018 Mar 27.
• [11] Hospital-acquired conditions and length of stay in the pregnancy and puerperal cycle.Rev Saude Publica. 2019 Aug 19;53:64. doi: 10.11606/s1518-8787.2019053000688.
• [12] Epidemiology of hepatic encephalopathy in german hospitals - the EpHE study.Z Gastroenterol. 2017 Aug;55(8):741-747. doi: 10.1055/s-0043-114671. Epub 2017 Jul 12.
• [13] Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis.Sci Rep. 2017 Feb 9;7:42304. doi: 10.1038/srep42304.
• [14] NaV1.6 and NaV1.7 channels are major endogenous voltage-gated sodium channels in ND7/23 cells.PLoS One. 2019 Aug 16;14(8):e0221156. doi: 10.1371/journal.pone.0221156. eCollection 2019.
• [15] Family-based association study of the MCF2L2 gene and polycystic ovary syndrome.Gynecol Obstet Invest. 2009;68(3):171-3. doi: 10.1159/000231520. Epub 2009 Jul 31.
• [16] A Novel SCN9A Mutation (F826Y) in Primary Erythromelalgia Alters the Excitability of Nav1.7.Curr Mol Med. 2017;17(6):450-457. doi: 10.2174/1566524017666171009105029.
• [17] Pain management using photobiomodulation: Mechanisms, location, and repeatability quantified by pain threshold and neural biomarkers in mice.J Biophotonics. 2018 Jul;11(7):e201700370. doi: 10.1002/jbio.201700370. Epub 2018 May 18.
• [18] Baicalin Depresses the Sympathoexcitatory Reflex Induced by Myocardial Ischemia via the Dorsal Root Ganglia.Front Physiol. 2018 Jul 17;9:928. doi: 10.3389/fphys.2018.00928. eCollection 2018.
• [19] Pharmacological targeting of the mammalian clock reveals a novel analgesic for osteoarthritis-induced pain.Gene. 2018 May 20;655:1-12. doi: 10.1016/j.gene.2018.02.048. Epub 2018 Feb 20.
• [20] STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.J Neuroimmunol. 2017 May 15;306:76-82. doi: 10.1016/j.jneuroim.2017.03.008. Epub 2017 Mar 11.
• [21] Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus.BMC Med Genet. 2010 Jul 28;11:116. doi: 10.1186/1471-2350-11-116.
• [22] Improvement of pyridoxine-induced peripheral neuropathy by Cichorium intybus hydroalcoholic extract through GABAergic system.J Physiol Sci. 2019 May;69(3):465-476. doi: 10.1007/s12576-019-00659-8. Epub 2019 Feb 2.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [27] 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.
• [28] 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.
• [29] 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.