Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8EF7ZF)

• DOT Name: Peripheral plasma membrane protein CASK (CASK)
• Synonyms: hCASK; EC 2.7.11.1; Calcium/calmodulin-dependent serine protein kinase; Protein lin-2 homolog
• Gene Name: CASK
• Related Disease:
  Angelman syndrome
  FG syndrome 4
  Isolated congenital microcephaly
  Partington syndrome
  Pontocerebellar hypoplasia
  Retinoblastoma
  Rett syndrome
  Syndromic X-linked intellectual disability Najm type
  West syndrome
  X-linked syndromic intellectual disability
  Acinar cell carcinoma
  Carcinoma of esophagus
  Cerebellar disorder
  Coloboma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epileptic encephalopathy
  FG syndrome
  Focal segmental glomerulosclerosis
  Glioblastoma multiforme
  Glioma
  Infantile epileptic-dyskinetic encephalopathy
  Isolated cleft palate
  Microlissencephaly
  Mungan syndrome
  Neoplasm
  Neurodevelopmental disorder
  Parkinson disease
  Pathologic nystagmus
  Pervasive developmental disorder
  Stomach cancer
  X-linked intellectual disability
  Movement disorder
  Systemic mastocytosis
  Tuberous sclerosis
  Infantile spasm
  Acquired nystagmus
  Autism
  Autism spectrum disorder
  Carcinoma
  Intellectual disability
  Retinopathy
  Specific language impairment
  Undifferentiated carcinoma
• UniProt ID: CSKP_HUMAN
• PDB ID: 1KGD; 1KWA; 1ZL8; 3C0G; 3C0H; 3C0I; 3MFR; 3MFS; 3MFT; 3MFU; 3TAC; 6KMH; 7OAI; 7OAJ; 7OAK; 7OAL
• EC Number: 2.7.11.1
• Pfam ID: PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF07653
• Sequence:
  MADDDVLFEDVYELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKFTSSPGLSTEDLK
  REASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADLCFEIVKRADAGFVYSEAVASH
  YMRQILEALRYCHDNNIIHRDVKPHCVLLASKENSAPVKLGGFGVAIQLGESGLVAGGRV
  GTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKGKYKMNPR
  QWSHISESAKDLVRRMLMLDPAERITVYEALNHPWLKERDRYAYKIHLPETVEQLRKFNA
  RRKLKGAVLAAVSSHKFNSFYGDPPEELPDFSEDPTSSGLLAAERAVSQVLDSLEEIHAL
  TDCSEKDLDFLHSVFQDQHLHTLLDLYDKINTKSSPQIRNPPSDAVQRAKEVLEEISCYP
  ENNDAKELKRILTQPHFMALLQTHDVVAHEVYSDEALRVTPPPTSPYLNGDSPESANGDM
  DMENVTRVRLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMIHRQGTLHVGDEIREIN
  GISVANQTVEQLQKMLREMRGSITFKIVPSYRTQSSSCERDSPSTSRQSPANGHSSTNNS
  VSDLPSTTQPKGRQIYVRAQFEYDPAKDDLIPCKEAGIRFRVGDIIQIISKDDHNWWQGK
  LENSKNGTAGLIPSPELQEWRVACIAMEKTKQEQQASCTWFGKKKKQYKDKYLAKHNAVF
  DQLDLVTYEEVVKLPAFKRKTLVLLGAHGVGRRHIKNTLITKHPDRFAYPIPHTTRPPKK
  DEENGKNYYFVSHDQMMQDISNNEYLEYGSHEDAMYGTKLETIRKIHEQGLIAILDVEPQ
  ALKVLRTAEFAPFVVFIAAPTITPGLNEDESLQRLQKESDILQRTYAHYFDLTIINNEID
  ETIRHLEEAVELVCTAPQWVPVSWVY
• Function: Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking. Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules.
• Tissue Specificity: Ubiquitous. Expression is significantly greater in brain relative to kidney, lung, and liver and in fetal brain and kidney relative to lung and liver.
• Reactome Pathway:
  Syndecan interactions (R-HSA-3000170)
  Nephrin family interactions (R-HSA-373753)
  Neurexins and neuroligins (R-HSA-6794361)
  Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Definitive	Genetic Variation	[1]
FG syndrome 4	DISBR29S	Definitive	X-linked	[2]
Isolated congenital microcephaly	DISUXHZ6	Definitive	Genetic Variation	[3]
Partington syndrome	DIS3H205	Definitive	Biomarker	[4]
Pontocerebellar hypoplasia	DISRICMU	Definitive	Genetic Variation	[5]
Retinoblastoma	DISVPNPB	Definitive	Biomarker	[6]
Rett syndrome	DISGG5UV	Definitive	Genetic Variation	[1]
Syndromic X-linked intellectual disability Najm type	DISP9PS7	Definitive	X-linked	[7]
West syndrome	DISLIAU9	Definitive	Biomarker	[8]
X-linked syndromic intellectual disability	DISG1YOH	Definitive	X-linked	[9]
Acinar cell carcinoma	DIS37Y0J	Strong	Biomarker	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[11]
Cerebellar disorder	DIS2O7WM	Strong	Biomarker	[12]
Coloboma	DISP39N5	Strong	Biomarker	[13]
Colon cancer	DISVC52G	Strong	Biomarker	[14]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[15]
Epileptic encephalopathy	DISZOCA3	Strong	GermlineCausalMutation	[16]
FG syndrome	DIS2MEFU	Strong	Genetic Variation	[16]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Biomarker	[17]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[18]
Glioma	DIS5RPEH	Strong	Biomarker	[18]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Genetic Variation	[16]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[19]
Microlissencephaly	DISUCKNT	Strong	Biomarker	[12]
Mungan syndrome	DISNR0AY	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[18]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[21]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[22]
Pathologic nystagmus	DIS1QSPO	Strong	Genetic Variation	[23]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[24]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[11]
X-linked intellectual disability	DISYJBY3	Strong	Biomarker	[4]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[25]
Systemic mastocytosis	DISNQ2OY	moderate	Biomarker	[26]
Tuberous sclerosis	DISEMUGZ	moderate	Biomarker	[27]
Infantile spasm	DISZSKDG	Supportive	Autosomal dominant	[28]
Acquired nystagmus	DISMYF5H	Limited	Genetic Variation	[23]
Autism	DISV4V1Z	Limited	Genetic Variation	[29]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[30]
Carcinoma	DISH9F1N	Limited	Biomarker	[31]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[5]
Retinopathy	DISB4B0F	Limited	Biomarker	[32]
Specific language impairment	DISEKRML	Limited	Genetic Variation	[29]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[31]

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 Peripheral plasma membrane protein CASK (CASK).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peripheral plasma membrane protein CASK (CASK).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Peripheral plasma membrane protein CASK (CASK).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Peripheral plasma membrane protein CASK (CASK).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peripheral plasma membrane protein CASK (CASK).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peripheral plasma membrane protein CASK (CASK).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Peripheral plasma membrane protein CASK (CASK).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[41]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol affects the expression of Peripheral plasma membrane protein CASK (CASK).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Peripheral plasma membrane protein CASK (CASK).	[44]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Peripheral plasma membrane protein CASK (CASK).	[45]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Peripheral plasma membrane protein CASK (CASK).	[46]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Peripheral plasma membrane protein CASK (CASK).	[48]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[49]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Peripheral plasma membrane protein CASK (CASK).	[39]

References

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