Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ1CQA2)

• DOT Name: Clathrin interactor 1 (CLINT1)
• Synonyms: Clathrin-interacting protein localized in the trans-Golgi region; Clint; Enthoprotin; Epsin-4; Epsin-related protein; EpsinR
• Gene Name: CLINT1
• Related Disease: Psychotic disorder
• UniProt ID: EPN4_HUMAN
• PDB ID: 1XGW; 2QY7; 2V8S
• Pfam ID: PF01417
• Sequence:
  MLNMWKVRELVDKATNVVMNYSEIESKVREATNDDPWGPSGQLMGEIAKATFMYEQFPEL
  MNMLWSRMLKDNKKNWRRVYKSLLLLAYLIRNGSERVVTSAREHIYDLRSLENYHFVDEH
  GKDQGINIRQKVKELVEFAQDDDRLREERKKAKKNKDKYVGVSSDSVGGFRYSERYDPEP
  KSKWDEEWDKNKSAFPFSDKLGELSDKIGSTIDDTISKFRRKDREDSPERCSDSDEEKKA
  RRGRSPKGEFKDEEETVTTKHIHITQATETTTTRHKRTANPSKTIDLGAAAHYTGDKASP
  DQNASTHTPQSSVKTSVPSSKSSGDLVDLFDGTSQSTGGSADLFGGFADFGSAAASGSFP
  SQVTATSGNGDFGDWSAFNQAPSGPVASSGEFFGSASQPAVELVSGSQSALGPPPAASNS
  SDLFDLMGSSQATMTSSQSMNFSMMSTNTVGLGLPMSRSQNTDMVQKSVSKTLPSTWSDP
  SVNISLDNLLPGMQPSKPQQPSLNTMIQQQNMQQPMNVMTQSFGAVNLSSPSNMLPVRPQ
  TNALIGGPMPMSMPNVMTGTMGMAPLGNTPMMNQSMMGMNMNIGMSAAGMGLTGTMGMGM
  PNIAMTSGTVQPKQDAFANFANFSK
• Function: Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly.
• Tissue Specificity: Ubiquitously expressed at low to intermediate levels.
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Clathrin interactor 1 (CLINT1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Clathrin interactor 1 (CLINT1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Clathrin interactor 1 (CLINT1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Clathrin interactor 1 (CLINT1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Clathrin interactor 1 (CLINT1).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Clathrin interactor 1 (CLINT1).	[8]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Clathrin interactor 1 (CLINT1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Clathrin interactor 1 (CLINT1).	[7]

References

• [1] The epsin 4 gene is associated with psychotic disorders in families of Latin American origin.Schizophr Res. 2008 Dec;106(2-3):253-7. doi: 10.1016/j.schres.2008.09.005. Epub 2008 Oct 17.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [9] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.