Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAP9L2A)

DOT Name Keratocan (KERA)
Synonyms KTN; Keratan sulfate proteoglycan keratocan
Gene Name KERA
Related Disease
Angle-closure glaucoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Connective tissue disorder ( )
Cornea plana ( )
Cornea plana 2 ( )
Myopia ( )
Peters anomaly ( )
Primary angle-closure glaucoma ( )
Keratoconus ( )
Obsolete congenital cornea plana ( )
Glaucoma/ocular hypertension ( )
UniProt ID
KERA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF13516 ; PF13855 ; PF01462
Sequence
MAGTICFIMWVLFITDTVWSRSVRQVYEVHDSDDWTIHDFECPMECFCPPSFPTALYCEN
RGLKEIPAIPSRIWYLYLQNNLIETIPEKPFENATQLRWINLNKNKITNYGIEKGALSQL
KKLLFLFLEDNELEEVPSPLPRSLEQLQLARNKVSRIPQGTFSNLENLTLLDLQNNKLVD
NAFQRDTFKGLKNLMQLNMAKNALRNMPPRLPANTMQLFLDNNSIEGIPENYFNVIPKVA
FLRLNHNKLSDEGLPSRGFDVSSILDLQLSHNQLTKVPRISAHLQHLHLDHNKIKSVNVS
VICPSPSMLPAERDSFSYGPHLRYLRLDGNEIKPPIPMALMTCFRLLQAVII
Function May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix.
Tissue Specificity Cornea (at protein level) . Increased expression in the stroma of keratoconus corneas . Also detected in trachea, and in low levels, in intestine, skeletal muscle, ovary, lung and putamen .
Reactome Pathway
Keratan sulfate degradation (R-HSA-2022857 )
Defective CHST6 causes MCDC1 (R-HSA-3656225 )
Defective ST3GAL3 causes MCT12 and EIEE15 (R-HSA-3656243 )
Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244 )
Keratan sulfate biosynthesis (R-HSA-2022854 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Angle-closure glaucoma DISZ95KY Strong Genetic Variation [1]
Arteriosclerosis DISK5QGC Strong Genetic Variation [2]
Atherosclerosis DISMN9J3 Strong Genetic Variation [2]
Connective tissue disorder DISKXBS3 Strong Genetic Variation [3]
Cornea plana DISE38HI Strong Genetic Variation [4]
Cornea plana 2 DISMALYT Strong Autosomal recessive [5]
Myopia DISK5S60 Strong Biomarker [3]
Peters anomaly DISERK0M Strong Biomarker [6]
Primary angle-closure glaucoma DISX8UKZ Strong Genetic Variation [1]
Keratoconus DISOONXH moderate Altered Expression [7]
Obsolete congenital cornea plana DIS6FVOP Supportive Autosomal dominant [5]
Glaucoma/ocular hypertension DISLBXBY Limited Genetic Variation [8]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Keratocan (KERA). [9]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Keratocan (KERA). [10]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Keratocan (KERA). [11]
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References

1 A Novel KERA Mutation in a Case of Autosomal Recessive Cornea Plana With Primary Angle-Closure Glaucoma.J Glaucoma. 2016 Feb;25(2):e106-9. doi: 10.1097/IJG.0000000000000258.
2 Mutation in KERA identified by linkage analysis and targeted resequencing in a pedigree with premature atherosclerosis.PLoS One. 2014 May 30;9(5):e98289. doi: 10.1371/journal.pone.0098289. eCollection 2014.
3 Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.Nat Commun. 2018 May 14;9(1):1864. doi: 10.1038/s41467-018-03646-6.
4 Novel variants in the KERA gene cause autosomal recessive cornea plana in a Chinese family: A case report.Mol Med Rep. 2019 Jun;19(6):4711-4718. doi: 10.3892/mmr.2019.10153. Epub 2019 Apr 11.
5 Mutations in KERA, encoding keratocan, cause cornea plana. Nat Genet. 2000 May;25(1):91-5. doi: 10.1038/75664.
6 Keratocan and lumican regulate neutrophil infiltration and corneal clarity in lipopolysaccharide-induced keratitis by direct interaction with CXCL1.J Biol Chem. 2007 Dec 7;282(49):35502-9. doi: 10.1074/jbc.M705823200. Epub 2007 Oct 2.
7 Keratocan expression is increased in the stroma of keratoconus corneas.Mol Med. 2001 Jul;7(7):470-7.
8 Roles of lumican and keratocan on corneal transparency.Glycoconj J. 2002 May-Jun;19(4-5):275-85. doi: 10.1023/A:1025396316169.
9 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
10 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
11 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.