Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60SNXQ)

DOT Name FERM and PDZ domain-containing protein 4 (FRMPD4)
Synonyms PDZ domain-containing protein 10; PSD-95-interacting regulator of spine morphogenesis; Preso
Gene Name FRMPD4
Related Disease
X-linked complex neurodevelopmental disorder ( )
Intellectual disability ( )
Intellectual disability, X-linked 1 ( )
Intellectual disability, X-linked 104 ( )
Schizophrenia ( )
Non-syndromic X-linked intellectual disability ( )
UniProt ID
FRPD4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4WND; 4WNE; 4WNF; 4WNG; 7BYJ
Pfam ID
PF21477 ; PF00373 ; PF00595
Sequence
MDVFSFVKIAKLSSHRTKSSGWPPPSGTWGLSQVPPYGWEMTANRDGRDYFINHMTQAIP
FDDPRLESCQIIPPAPRKVEMRRDPVLGFGFVAGSEKPVVVRSVTPGGPSEGKLIPGDQI
VMINDEPVSAAPRERVIDLVRSCKESILLTVIQPYPSPKSAFISAAKKARLKSNPVKVRF
SEEVIINGQVSETVKDNSLLFMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIK
GIEHFSLMLEQRTEGAGTKLLLLHEQETLTQVTQRPSSHKMRCLFRISFVPKDPIDLLRR
DPVAFEYLYVQSCNDVVQERFGPELKYDIALRLAALQMYIATVTTKQTQKISLKYIEKEW
GLETFLPSAVLQSMKEKNIKKALSHLVKANQNLVPPGKKLSALQAKVHYLKFLSDLRLYG
GRVFKATLVQAEKRSEVTLLVGPRYGISHVINTKTNLVALLADFSHVNRIEMFSEEESLV
RVELHVLDVKPITLLMESSDAMNLACLTAGYYRLLVDSRRSIFNMANKKNTATQETGPEN
KGKHNLLGPDWNCIPQMTTFIGEGEQEAQITYIDSKQKTVEITDSTMCPKEHRHLYIDNA
YSSDGLNQQLSQPGEAPCEADYRSLAQRSLLTLSGPETLKKAQESPRGAKVSFIFGDFAL
DDGISPPTLGYETLLDEGPEMLEKQRNLYIGSANDMKGLDLTPEAEGIQFVENSVYANIG
DVKSFQAAEGIEEPLLHDICYAENTDDAEDEDEVSCEEDLVVGEMNQPAILNLSGSSDDI
IDLTSLPPPEGDDNEDDFLLRSLNMAIAAPPPGFRDSSDEEDSQSQAASFPEDKEKGSSL
QNDEIPVSLIDAVPTSAEGKCEKGLDNAVVSTLGALEALSVSEEQQTSDNSGVAILRAYS
PESSSDSGNETNSSEMTESSELATAQKQSENLSRMFLATHEGYHPLAEEQTEFPASKTPA
GGLPPKSSHALAARPATDLPPKVVPSKQLLHSDHMEMEPETMETKSVTDYFSKLHMGSVA
YSCTSKRKSKLADGEGKAPPNGNTTGKKQQGTKTAEMEEEASGKFGTVSSRDSQHLSTFN
LERTAFRKDSQRWYVATEGGMAEKSGLEAATGKTFPRASGLGAREAEGKEEGAPDGETSD
GSGLGQGDRFLTDVTCASSAKDLDNPEDADSSTCDHPSKLPEADESVARLCDYHLAKRMS
SLQSEGHFSLQSSQGSSVDAGCGTGSSGSACATPVESPLCPSLGKHLIPDASGKGVNYIP
SEERAPGLPNHGATFKELHPQTEGMCPRMTVPALHTAINTEPLFGTLRDGCHRLPKIKET
TV
Function Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
X-linked complex neurodevelopmental disorder DISI3QE9 Definitive X-linked [1]
Intellectual disability DISMBNXP Strong Genetic Variation [2]
Intellectual disability, X-linked 1 DISET38E Strong GermlineCausalMutation [3]
Intellectual disability, X-linked 104 DISTBWL2 Strong X-linked [4]
Schizophrenia DISSRV2N Strong Genetic Variation [5]
Non-syndromic X-linked intellectual disability DIS71AI3 Supportive X-linked [3]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of FERM and PDZ domain-containing protein 4 (FRMPD4). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of FERM and PDZ domain-containing protein 4 (FRMPD4). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of FERM and PDZ domain-containing protein 4 (FRMPD4). [12]
------------------------------------------------------------------------------------
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of FERM and PDZ domain-containing protein 4 (FRMPD4). [7]
Triclosan DMZUR4N Approved Triclosan decreases the expression of FERM and PDZ domain-containing protein 4 (FRMPD4). [8]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of FERM and PDZ domain-containing protein 4 (FRMPD4). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of FERM and PDZ domain-containing protein 4 (FRMPD4). [11]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of FERM and PDZ domain-containing protein 4 (FRMPD4). [13]
------------------------------------------------------------------------------------

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 FRMPD4 mutations cause X-linked intellectual disability and disrupt dendritic spine morphogenesis.Hum Mol Genet. 2018 Feb 15;27(4):589-600. doi: 10.1093/hmg/ddx426.
3 X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Mol Psychiatry. 2016 Jan;21(1):133-48. doi: 10.1038/mp.2014.193. Epub 2015 Feb 3.
4 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
5 Possibility of a sex-specific role for a genetic variant in FRMPD4 in schizophrenia, but not cognitive function.Neuroreport. 2016 Jan 6;27(1):33-8. doi: 10.1097/WNR.0000000000000491.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9 Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
10 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.
11 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.
12 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.
13 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.