Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA6M8M4)

• DOT Name: Cysteine-rich PDZ-binding protein (CRIPT)
• Synonyms: Cysteine-rich interactor of PDZ three; Cysteine-rich interactor of PDZ3
• Gene Name: CRIPT
• Related Disease:
  Isolated growth hormone deficiency type IA
  Short stature with microcephaly and distinctive facies
• UniProt ID: CRIPT_HUMAN
• PDB ID: 7DVQ
• Pfam ID: PF10235
• Sequence:
  MVCEKCEKKLGTVITPDTWKDGARNTTESGGRKLNENKALTSKKARFDPYGKNKFSTCRI
  CKSSVHQPGSHYCQGCAYKKGICAMCGKKVLDTKNYKQTSV
• Function: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in the cytoskeletal anchoring of DLG4 in excitatory synapses.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated growth hormone deficiency type IA	DISLPIAM	Definitive	Genetic Variation	[1]
Short stature with microcephaly and distinctive facies	DIS8AUSD	Strong	Autosomal recessive	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Cysteine-rich PDZ-binding protein (CRIPT) affects the response to substance of Vinblastine.	[16]

2 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 Cysteine-rich PDZ-binding protein (CRIPT).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cysteine-rich PDZ-binding protein (CRIPT).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cysteine-rich PDZ-binding protein (CRIPT).	[15]

References

• [1] CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.Am J Med Genet A. 2016 Aug;170(8):2206-11. doi: 10.1002/ajmg.a.37780. Epub 2016 Jun 2.
• [2] Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res. 2014 Feb;24(2):291-9. doi: 10.1101/gr.160572.113. Epub 2014 Jan 3.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.