Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07035C)

• DOT Name: Protein YIPF5
• Synonyms: Five-pass transmembrane protein localizing in the Golgi apparatus and the endoplasmic reticulum 5; Smooth muscle cell-associated protein 5; SMAP-5; YIP1 family member 5; YPT-interacting protein 1 A
• Gene Name: YIPF5
• Related Disease:
  Microcephaly, epilepsy, and diabetes syndrome 2
  Obsolete primary microcephaly-epilepsy-permanent neonatal diabetes syndrome
• UniProt ID: YIPF5_HUMAN
• Pfam ID: PF04893
• Sequence:
  MSGFENLNTDFYQTSYSIDDQSQQSYDYGGSGGPYSKQYAGYDYSQQGRFVPPDMMQPQQ
  PYTGQIYQPTQAYTPASPQPFYGNNFEDEPPLLEELGINFDHIWQKTLTVLHPLKVADGS
  IMNETDLAGPMVFCLAFGATLLLAGKIQFGYVYGISAIGCLGMFCLLNLMSMTGVSFGCV
  ASVLGYCLLPMILLSSFAVIFSLQGMVGIILTAGIIGWCSFSASKIFISALAMEGQQLLV
  AYPCALLYGVFALISVF
• Function: Plays a role in transport between endoplasmic reticulum and Golgi. In pancreatic beta cells, required to transport proinsulin from endoplasmic reticulum into the Golgi.
• Tissue Specificity: Ubiquitously expressed with abundant expression in pancreatic tissue, islets, beta cells, and brain. Highly expressed in coronary smooth muscles.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microcephaly, epilepsy, and diabetes syndrome 2	DISLC5RW	Strong	Autosomal recessive	[1]
Obsolete primary microcephaly-epilepsy-permanent neonatal diabetes syndrome	DISK2F5H	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein YIPF5.	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein YIPF5.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein YIPF5.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein YIPF5.	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein YIPF5.	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein YIPF5.	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein YIPF5.	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein YIPF5.	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein YIPF5.	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein YIPF5.	[12]

References

• [1] YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress. J Clin Invest. 2020 Dec 1;130(12):6338-6353. doi: 10.1172/JCI141455.
• [2] YIPF5 mutations cause neonatal diabetes and microcephaly: progress for precision medicine and mechanistic understanding. J Clin Invest. 2020 Dec 1;130(12):6228-6231. doi: 10.1172/JCI142364.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.