Details of Drug Off-Target (DOT)

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

DOT Name Gap junction alpha-8 protein (GJA8)
Synonyms Connexin-50; Cx50; Lens fiber protein MP70
Gene Name GJA8
Related Disease
Cataract 1 multiple types ( )
Cataract - microcornea syndrome ( )
Early-onset nuclear cataract ( )
Early-onset sutural cataract ( )
Pulverulent cataract ( )
Total early-onset cataract ( )
UniProt ID
CXA8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00029 ; PF03509
Sequence
MGDWSFLGNILEEVNEHSTVIGRVWLTVLFIFRILILGTAAEFVWGDEQSDFVCNTQQPG
CENVCYDEAFPISHIRLWVLQIIFVSTPSLMYVGHAVHYVRMEEKRKSREAEELGQQAGT
NGGPDQGSVKKSSGSKGTKKFRLEGTLLRTYICHIIFKTLFEVGFIVGHYFLYGFRILPL
YRCSRWPCPNVVDCFVSRPTEKTIFILFMLSVASVSLFLNVMELGHLGLKGIRSALKRPV
EQPLGEIPEKSLHSIAVSSIQKAKGYQLLEEEKIVSHYFPLTEVGMVETSPLPAKPFNQF
EEKISTGPLGDLSRGYQETLPSYAQVGAQEVEGEGPPAEEGAEPEVGEKKEEAERLTTEE
QEKVAVPEGEKVETPGVDKEGEKEEPQSEKVSKQGLPAEKTPSLCPELTTDDARPLSRLS
KASSRARSDDLTV
Function
Structural component of eye lens gap junctions. Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore.
Tissue Specificity Eye lens.
Reactome Pathway
Gap junction assembly (R-HSA-190861 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cataract 1 multiple types DIS5M02Q Definitive Autosomal dominant [1]
Cataract - microcornea syndrome DISL51AQ Supportive Autosomal dominant [2]
Early-onset nuclear cataract DISGIHUY Supportive Autosomal dominant [3]
Early-onset sutural cataract DISKFS14 Supportive Autosomal dominant [4]
Pulverulent cataract DISMJ2AH Supportive Autosomal dominant [5]
Total early-onset cataract DISACMEZ Supportive Autosomal dominant [6]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Gap junction alpha-8 protein (GJA8). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Gap junction alpha-8 protein (GJA8). [10]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Gap junction alpha-8 protein (GJA8). [8]
Tetracycline DMZA017 Approved Tetracycline decreases the expression of Gap junction alpha-8 protein (GJA8). [9]
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References

1 New mutations in GJA8 expand the phenotype to include total sclerocornea. Clin Genet. 2018 Jan;93(1):155-159. doi: 10.1111/cge.13045. Epub 2017 Sep 8.
2 A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree. Mol Vis. 2010 Aug 11;16:1585-92.
3 A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract. J Med Genet. 2003 Nov;40(11):e124. doi: 10.1136/jmg.40.11.e124.
4 A mutation in GJA8 (p.P88Q) is associated with "balloon-like" cataract with Y-sutural opacities in a family of Indian origin. Mol Vis. 2008 Jun 17;14:1171-5.
5 A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet. 2008 Mar;45(3):155-60. doi: 10.1136/jmg.2007.051029. Epub 2007 Nov 15.
6 Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract. J Med Genet. 2007 Jul;44(7):e85. doi: 10.1136/jmg.2007.050138.
7 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
8 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
9 Effects of residual levels of tetracycline on the barrier functions of human intestinal epithelial cells. Food Chem Toxicol. 2017 Nov;109(Pt 1):253-263. doi: 10.1016/j.fct.2017.09.004. Epub 2017 Sep 4.
10 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.