Details of Drug Off-Target (DOT)

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

• DOT Name: Late cornified envelope protein 3D (LCE3D)
• Synonyms: Late envelope protein 16; Small proline-rich-like epidermal differentiation complex protein 6A; Small proline-rich-like epidermal differentiation complex protein 6B
• Gene Name: LCE3D
• Related Disease:
  Palmoplantar pustulosis
  Psoriasis
• UniProt ID: LCE3D_HUMAN
• Pfam ID: PF14672
• Sequence:
  MSCQQNQQQCQPPPKCPSPKCPPKSPVQCLPPASSGCAPSSGGCGPSSEGGCFLNHHRRH
  HRCRRQRPNSCDRGSGQQGGGSGCGHGSGGCC
• Function: Precursors of the cornified envelope of the stratum corneum.
• Tissue Specificity: Skin-specific. Expression was readily detected in adult trunk skin, adult arm skin, fetal skin, penal skin, vulva, esophagus and tongue. Not expressed in the cervix, rectum, lung, colon, or placenta.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[1]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]

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 Late cornified envelope protein 3D (LCE3D).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Late cornified envelope protein 3D (LCE3D).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Late cornified envelope protein 3D (LCE3D).	[3]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Late cornified envelope protein 3D (LCE3D).	[3]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Late cornified envelope protein 3D (LCE3D).	[3]

References

• [1] A large-scale screen for coding variants predisposing to psoriasis.Nat Genet. 2014 Jan;46(1):45-50. doi: 10.1038/ng.2827. Epub 2013 Nov 10.
• [2] 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.
• [3] Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation. J Dermatol Sci. 2014 Nov;76(2):112-9. doi: 10.1016/j.jdermsci.2014.08.003. Epub 2014 Aug 26.
• [4] 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.