Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8OM5MA)

• DOT Name: FERM and PDZ domain-containing protein 2 (FRMPD2)
• Synonyms: PDZ domain-containing protein 4; PDZ domain-containing protein 5C
• Gene Name: FRMPD2
• Related Disease:
  Narcolepsy
  Synovial sarcoma
  Clear cell renal carcinoma
  Myopia
• UniProt ID: FRPD2_HUMAN
• Pfam ID: PF09380 ; PF00373 ; PF09379 ; PF00595
• Sequence:
  MQPLTKDAGMSLSSVTLASALQVRGEALSEEEIWSLLFLAAEQLLEDLRNDSSDYVVCPW
  SALLSAAGSLSFQGRVSHIEAAPFKAPELLQGQSEDEQPDASQMHVYSLGMTLYWSAGFH
  VPPHQPLQLCEPLHSILLTMCEDQPHRRCTLQSVLEACRVHEKEVSVYPAPAGLHIRRLV
  GLVLGTISEVEKRVVEESSSVQQNRSYLLRKRLRGTSSESPAAQAPECLHPCRVSERSTE
  TQSSPEPHWSTLTHSHCSLLVNRALPGADPQDQQAGRRLSSGSVHSAADSSWPTTPSQRG
  FLQRRSKFSRPEFILLAGEAPMTLHLPGSVVTKKGKSYLALRDLCVVLLNGQHLEVKCDV
  ESTVGAVFNAVTSFANLEELTYFGLAYMKSKEFFFLDSETRLCKIAPEGWREQPQKTSMN
  TFTLFLRIKFFVSHYGLLQHSLTRHQFYLQLRKDILEERLYCNEEILLQLGVLALQAEFG
  NYPKEQVESKPYFHVEDYIPASLIERMTALRVQVEVSEMHRLSSALWGEDAELKFLRVTQ
  QLPEYGVLVHQVFSEKRRPEEEMALGICAKGVIVYEVKNNSRIAMLRFQWRETGKISTYQ
  KKFTITSSVTGKKHTFVTDSAKTSKYLLDLCSAQHGFNAQMGSGQPSHVLFDHDKFVQMA
  NLSPAHQARSKPLIWIQRLSCSENELFVSRLQGAAGGLLSTSMDNFNVDGSKEAGAEGIG
  RSPCTGREQLKSACVIQKPMTWDSLSGPPVQSMHAGSKNNRRKSFIAEPGREIVRVTLKR
  DPHRGFGFVINEGEYSGQADPGIFISSIIPGGPAEKAKTIKPGGQILALNHISLEGFTFN
  MAVRMIQNSPDNIELIISQSKGVGGNNPDEEKNSTANSGVSSTDILSFGYQGSLLSHTQD
  QDRNTEELDMAGVQSLVPRLRHQLSFLPLKGAGSSCPPSPPEISAGEIYFVELVKEDGTL
  GFSVTGGINTSVPYGGIYVKSIVPGGPAAKEGQILQGDRLLQVDGVILCGLTHKQAVQCL
  TGPGQVARLVLERRVPRSTQQCPSANDSMGDERTAVSLVTALPGRPSSCVSVTDGPKFEV
  KLKKNANGLGFSFVQMEKESCSHLKSDLVRIKRLFPGQPAEENGAIAAGDIILAVNGRST
  EGLIFQEVLHLLRGAPQEVTLLLCRPPPGALPELEQEWQTPELSADKEFTRATCTDSCTS
  PILDQEDSWRDSASPDAGEGLGLRPESSQKAIREAQWGQNRERPWASSLTHSPESHPHLC
  KLHQERDESTLATSLEKDVRQNCYSVCDIMRLGRYSFSSPLTRLSTDIF
• Function: May play a role in the regulation of tight junction formation. Binds phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
• Tissue Specificity: Expressed in epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[1]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[2]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[3]
Myopia	DISK5S60	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[9]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[12]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[10]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of FERM and PDZ domain-containing protein 2 (FRMPD2).	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of FERM and PDZ domain-containing protein 2 (FRMPD2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of FERM and PDZ domain-containing protein 2 (FRMPD2).	[11]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas.Oncogene. 2004 Jul 15;23(32):5551-7. doi: 10.1038/sj.onc.1207710.
• [3] Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer.Sci Rep. 2017 Mar 28;7:44997. doi: 10.1038/srep44997.
• [4] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [5] 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.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [11] 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.
• [12] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [13] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.