Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5D60QU)

• DOT Name: Protein disulfide-isomerase-like protein of the testis (PDILT)
• Gene Name: PDILT
• Related Disease:
  Chronic renal failure
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Cardiovascular disease
  Urolithiasis
• UniProt ID: PDILT_HUMAN
• PDB ID: 4NWY; 5XF7
• Pfam ID: PF00085 ; PF13848
• Sequence:
  MDLLWMPLLLVAACVSAVHSSPEVNAGVSSIHITKPVHILEERSLLVLTPAGLTQMLNQT
  RFLMVLFHNPSSKQSRNLAEELGKAVEIMGKGKNGIGFGKVDITIEKELQQEFGITKAPE
  LKLFFEGNRSEPISCKGVVESAALVVWLRRQISQKAFLFNSSEQVAEFVISRPLVIVGFF
  QDLEEEVAELFYDVIKDFPELTFGVITIGNVIGRFHVTLDSVLVFKKGKIVNRQKLINDS
  TNKQELNRVIKQHLTDFVIEYNTENKDLISELHIMSHMLLFVSKSSESYGIIIQHYKLAS
  KEFQNKILFILVDADEPRNGRVFKYFRVTEVDIPSVQILNLSSDARYKMPSDDITYESLK
  KFGRSFLSKNATKHQSSEEIPKYWDQGLVKQLVGKNFNVVVFDKEKDVFVMFYAPWSKKC
  KMLFPLLEELGRKYQNHSTIIIAKIDVTANDIQLMYLDRYPFFRLFPSGSQQAVLYKGEH
  TLKGFSDFLESHIKTKIEDEDELLSVEQNEVIEEEVLAEEKEVPMMRKGLPEQQSPELEN
  MTKYVSKLEEPAGKKKTSEEVVVVVAKPKGPPVQKKKPKVKEEL
• Function: Probable redox-inactive chaperone involved in spermatogenesis.
• Tissue Specificity: Testis-specific.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Genetic Variation	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Urolithiasis	DISNFTKT	Limited	Genetic Variation	[4]

2 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 Protein disulfide-isomerase-like protein of the testis (PDILT).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein disulfide-isomerase-like protein of the testis (PDILT).	[6]

References

• [1] A catalog of genetic loci associated with kidney function from analyses of a million individuals.Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.
• [2] A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.Diabetes. 2018 Jul;67(7):1414-1427. doi: 10.2337/db17-0914. Epub 2018 Apr 27.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population.J Am Soc Nephrol. 2019 May;30(5):855-864. doi: 10.1681/ASN.2018090942. Epub 2019 Apr 11.
• [5] 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.
• [6] 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.