Details of Drug Off-Target (DOT)

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

• DOT Name: Serine protease 56 (PRSS56)
• Synonyms: EC 3.4.21.-
• Gene Name: PRSS56
• Related Disease:
  Isolated microphthalmia 6
  Microphthalmia
  Primary angle-closure glaucoma
  Refractive error
  Angle-closure glaucoma
  Nanophthalmia
  Myopia
• UniProt ID: PRS56_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MLLAVLLLLPLPSSWFAHGHPLYTRLPPSALQVLSAQGTQALQAAQRSAQWAINRVAMEI
  QHRSHECRGSGRPRPQALLQDPPEPGPCGERRPSTANVTRAHGRIVGGSAAPPGAWPWLV
  RLQLGGQPLCGGVLVAASWVLTAAHCFVGAPNELLWTVTLAEGSRGEQAEEVPVNRILPH
  PKFDPRTFHNDLALVQLWTPVSPGGSARPVCLPQEPQEPPAGTACAIAGWGALFEDGPEA
  EAVREARVPLLSTDTCRRALGPGLRPSTMLCAGYLAGGVDSCQGDSGGPLTCSEPGPRPR
  EVLFGVTSWGDGCGEPGKPGVYTRVAVFKDWLQEQMSASSSREPSCRELLAWDPPQELQA
  DAARLCAFYARLCPGSQGACARLAHQQCLQRRRRCELRSLAHTLLGLLRNAQELLGPRPG
  LRRLAPALALPAPALRESPLHPARELRLHSGSRAAGTRFPKRRPEPRGEANGCPGLEPLR
  QKLAALQGAHAWILQVPSEHLAMNFHEVLADLGSKTLTGLFRAWVRAGLGGRHVAFSGLV
  GLEPATLARSLPRLLVQALQAFRVAALAEGEPEGPWMDVGQGPGLERKGHHPLNPQVPPA
  RQP
• Function: Serine protease required during eye development.
• Tissue Specificity: Expressed neural retina, cornea, sclera and optic nerve.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated microphthalmia 6	DISZR9L5	Definitive	Autosomal recessive	[1]
Microphthalmia	DISGEBES	Strong	Genetic Variation	[2]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[3]
Refractive error	DISWNEQ1	Strong	Biomarker	[4]
Angle-closure glaucoma	DISZ95KY	moderate	Genetic Variation	[3]
Nanophthalmia	DISIULDO	Supportive	Autosomal dominant	[5]
Myopia	DISK5S60	Limited	Posttranslational Modification	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine protease 56 (PRSS56).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serine protease 56 (PRSS56).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine protease 56 (PRSS56).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Serine protease 56 (PRSS56).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Serine protease 56 (PRSS56).	[10]

References

• [1] Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease. Am J Hum Genet. 2011 Mar 11;88(3):382-90. doi: 10.1016/j.ajhg.2011.02.006.
• [2] Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study.Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2904-2913. doi: 10.1167/iovs.18-26275.
• [3] Evaluation of PRSS56 in Chinese subjects with high hyperopia or primary angle-closure glaucoma.Mol Vis. 2013 Nov 7;19:2217-26. eCollection 2013.
• [4] Mller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.PLoS Genet. 2018 Mar 12;14(3):e1007244. doi: 10.1371/journal.pgen.1007244. eCollection 2018 Mar.
• [5] Mutations in a novel serine protease PRSS56 in families with nanophthalmos. Mol Vis. 2011;17:1850-61. Epub 2011 Jul 12.
• [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] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.