Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CD0VH)

• DOT Name: Matrilin-4 (MATN4)
• Gene Name: MATN4
• Related Disease:
  Corneal dystrophy
  Lattice corneal dystrophy type I
  Prostate cancer
  Prostate neoplasm
  Stromal corneal dystrophy
  Clear cell renal carcinoma
• UniProt ID: MATN4_HUMAN
• Pfam ID: PF12662 ; PF14670 ; PF10393 ; PF00092
• Sequence:
  MRGLLCWPVLLLLLQPWETQLQLTGPRCHTGPLDLVFVIDSSRSVRPFEFETMRQFLMGL
  LRGLNVGPNATRVGVIQYSSQVQSVFPLRAFSRREDMERAIRDLVPLAQGTMTGLAIQYA
  MNVAFSVAEGARPPEERVPRVAVIVTDGRPQDRVAEVAAQARARGIEIYAVGVQRADVGS
  LRAMASPPLDEHVFLVESFDLIQEFGLQFQSRLCGKDQCAEGGHGCQHQCVNAWAMFHCT
  CNPGYKLAADNKSCLAIDLCAEGTHGCEHHCVNSPGSYFCHCQVGFVLQQDQRSCRAIDY
  CSFGNHSCQHECVSTPGGPRCHCREGHDLQPDGRSCQVRDLCNGVDHGCEFQCVSEGLSY
  RCLCPEGRQLQADGKSCNRCREGHVDLVLLVDGSKSVRPQNFELVKRFVNQIVDFLDVSP
  EGTRVGLVQFSSRVRTEFPLGRYGTAAEVKQAVLAVEYMERGTMTGLALRHMVEHSFSEA
  QGARPRALNVPRVGLVFTDGRSQDDISVWAARAKEEGIVMYAVGVGKAVEAELREIASEP
  AELHVSYAPDFGTMTHLLENLRGSICPEEGISAGTELRSPCECESLVEFQGRTLGALESL
  TLNLAQLTARLEDLENQLANQK
• Function: Major component of the extracellular matrix of cartilage.
• Tissue Specificity: Embryonic kidney, lung and placenta.
• Reactome Pathway: ECM proteoglycans (R-HSA-3000178)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Corneal dystrophy	DISRDPA6	Strong	Altered Expression	[1]
Lattice corneal dystrophy type I	DISNKVHC	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Stromal corneal dystrophy	DIS41FDX	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[3]

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 Matrilin-4 (MATN4).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Matrilin-4 (MATN4).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Matrilin-4 (MATN4).	[5]

References

• [1] Fibrillin-2, tenascin-C, matrilin-2, and matrilin-4 are strongly expressed in the epithelium of human granular and lattice type I corneal dystrophies.Mol Vis. 2012;18:1927-36. Epub 2012 Jul 18.
• [2] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [3] Identification of a 5-Gene Signature Predicting Progression and Prognosis of Clear Cell Renal Cell Carcinoma.Med Sci Monit. 2019 Jun 13;25:4401-4413. doi: 10.12659/MSM.917399.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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.