Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DEZRM)

DOT Name Carbohydrate sulfotransferase 9 (CHST9)
Synonyms EC 2.8.2.-; GalNAc-4-O-sulfotransferase 2; GalNAc-4-ST2; GalNAc4ST-2; N-acetylgalactosamine-4-O-sulfotransferase 2
Gene Name CHST9
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Coronary heart disease ( )
Major depressive disorder ( )
Neoplasm ( )
Schizophrenia ( )
Triple negative breast cancer ( )
Acute lymphocytic leukaemia ( )
Acute myelogenous leukaemia ( )
Childhood myelodysplastic syndrome ( )
Myelodysplastic syndrome ( )
UniProt ID
CHST9_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.8.2.-
Pfam ID
PF03567
Sequence
MQPSEMVMNPKQVFLSVLIFGVAGLLLFMYLQVWIEEQHTGRVEKRREQKVTSGWGPVKY
LRPVPRIMSTEKIQEHITNQNPKFHMPEDVREKKENLLLNSERSTRLLTKTSHSQGGDQA
LSKSTGSPTEKLIEKRQGAKTVFNKFSNMNWPVDIHPLNKSLVKDNKWKKTEETQEKRRS
FLQEFCKKYGGVSHHQSHLFHTVSRIYVEDKHKILYCEVPKAGCSNWKRILMVLNGLASS
AYNISHNAVHYGKHLKKLDSFDLKGIYTRLNTYTKAVFVRDPMERLVSAFRDKFEHPNSY
YHPVFGKAIIKKYRPNACEEALINGSGVKFKEFIHYLLDSHRPVGMDIHWEKVSKLCYPC
LINYDFVGKFETLEEDANYFLQMIGAPKELKFPNFKDRHSSDERTNAQVVRQYLKDLTRT
ERQLIYDFYYLDYLMFNYTTPFL
Function
Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Participates in biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Has a higher activity toward carbonic anhydrase VI than toward lutropin. Only active against terminal GalNAcbeta1,GalNAcbeta. Isoform 2, but not isoform 1, is active toward chondroitin.
Tissue Specificity
Highly expressed in trachea. Also expressed in fetal lung, adult pancreas, testis and salivary gland. Expressed at low level in pituitary gland, apex of the heart, adult lung, prostate and mammary gland. Weakly or not expressed in heart, liver and spinal cord.
KEGG Pathway
Various types of N-glycan biosynthesis (hsa00513 )
Metabolic pathways (hsa01100 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Genetic Variation [1]
Breast carcinoma DIS2UE88 Strong Genetic Variation [2]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [3]
Major depressive disorder DIS4CL3X Strong Genetic Variation [3]
Neoplasm DISZKGEW Strong Genetic Variation [4]
Schizophrenia DISSRV2N Strong Genetic Variation [5]
Triple negative breast cancer DISAMG6N Strong Genetic Variation [4]
Acute lymphocytic leukaemia DISPX75S Disputed Biomarker [6]
Acute myelogenous leukaemia DISCSPTN Disputed Biomarker [6]
Childhood myelodysplastic syndrome DISMN80I Disputed Biomarker [6]
Myelodysplastic syndrome DISYHNUI Disputed Biomarker [6]
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⏷ Show the Full List of 11 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
Valproate DMCFE9I Approved Valproate decreases the methylation of Carbohydrate sulfotransferase 9 (CHST9). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Carbohydrate sulfotransferase 9 (CHST9). [15]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Carbohydrate sulfotransferase 9 (CHST9). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Carbohydrate sulfotransferase 9 (CHST9). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Carbohydrate sulfotransferase 9 (CHST9). [10]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Carbohydrate sulfotransferase 9 (CHST9). [11]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Carbohydrate sulfotransferase 9 (CHST9). [12]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Carbohydrate sulfotransferase 9 (CHST9). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Carbohydrate sulfotransferase 9 (CHST9). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Carbohydrate sulfotransferase 9 (CHST9). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Carbohydrate sulfotransferase 9 (CHST9). [16]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Carbohydrate sulfotransferase 9 (CHST9). [17]
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⏷ Show the Full List of 10 Drug(s)

References

1 Large-scale genotyping identifies 41 new loci associated with breast cancer risk.Nat Genet. 2013 Apr;45(4):353-61, 361e1-2. doi: 10.1038/ng.2563.
2 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
3 Association of Genetic Variation at AQP4 Locus with Vascular Depression.Biomolecules. 2018 Dec 5;8(4):164. doi: 10.3390/biom8040164.
4 CHST9 rs1436904 genetic variant contributes to prognosis of triple-negative breast cancer.Sci Rep. 2017 Sep 18;7(1):11802. doi: 10.1038/s41598-017-12306-6.
5 A Frameshift Variant in the CHST9 Gene Identified by Family-Based Whole Genome Sequencing Is Associated with Schizophrenia in Chinese Population.Sci Rep. 2019 Sep 3;9(1):12717. doi: 10.1038/s41598-019-49052-w.
6 Examination of copy number variations of CHST9 in multiple types of hematologic malignancies.Cancer Genet Cytogenet. 2010 Dec;203(2):176-9. doi: 10.1016/j.cancergencyto.2010.07.132.
7 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.
8 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
13 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 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.
16 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
17 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.