Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL2ENWI)

DOT Name HORMA domain-containing protein 2 (HORMAD2)
Gene Name HORMAD2
Related Disease
Breast carcinoma ( )
Hypothyroidism ( )
Lung cancer ( )
Lung carcinoma ( )
Multiple sclerosis ( )
Nephropathy ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Type-1 diabetes ( )
IgA nephropathy ( )
Ulcerative colitis ( )
Crohn disease ( )
Inflammatory bowel disease ( )
Neoplasm ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
UniProt ID
HORM2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02301
Sequence
MATAQLSHCITIHKASKETVFPSQITNEHESLKMVKKLFATSISCITYLRGLFPESSYGE
RHLDDLSLKILREDKKCPGSLHIIRWIQGCFDALEKRYLRMAVLTLYTDPMGSEKVTEMY
QFKFKYTKEGATMDFDSHSSSTSFESGTNNEDIKKASVLLIRKLYILMQDLEPLPNNVVL
TMKLHYYNAVTPHDYQPLGFKEGVNSHFLLFDKEPINVQVGFVSTGFHSMKVKVMTEATK
VIDLENNLFRENSTTEIAHQGLDCDEEEECNDHIQRMNFVCSQQSSECSRKKRKVSEPVK
VFIPNRK
Function
Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes. Required for the DNA double-strand break-independent, BRCA1-dependent activation of ATR on the sex chromosomes that is essential for normal sex body formation.
Tissue Specificity Highly expressed in testis (at protein level). Expressed in lung adenocarcinoma and squamous cell carcinoma (at protein level). Expressed at lower levels in the liver, brain and kidney.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast carcinoma DIS2UE88 Strong Genetic Variation [1]
Hypothyroidism DISR0H6D Strong Genetic Variation [2]
Lung cancer DISCM4YA Strong Genetic Variation [3]
Lung carcinoma DISTR26C Strong Genetic Variation [3]
Multiple sclerosis DISB2WZI Strong Genetic Variation [4]
Nephropathy DISXWP4P Strong Genetic Variation [5]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [6]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [3]
Type-1 diabetes DIS7HLUB Strong Genetic Variation [7]
IgA nephropathy DISZ8MTK moderate Genetic Variation [8]
Ulcerative colitis DIS8K27O moderate Genetic Variation [9]
Crohn disease DIS2C5Q8 Limited Genetic Variation [10]
Inflammatory bowel disease DISGN23E Limited Genetic Variation [10]
Neoplasm DISZKGEW Limited Altered Expression [11]
Thyroid cancer DIS3VLDH Limited Altered Expression [11]
Thyroid gland carcinoma DISMNGZ0 Limited Altered Expression [11]
Thyroid tumor DISLVKMD Limited Altered Expression [11]
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⏷ Show the Full List of 17 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 decreases the methylation of HORMA domain-containing protein 2 (HORMAD2). [12]
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References

1 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.
2 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
3 Association of polymorphisms at HORMAD2 and prognosis in advanced non-small-cell lung cancer patients.Cancer Epidemiol. 2014 Aug;38(4):414-8. doi: 10.1016/j.canep.2014.03.013. Epub 2014 May 3.
4 Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
5 Genome-wide association study identifies susceptibility loci for IgA nephropathy.Nat Genet. 2011 Mar 13;43(4):321-7. doi: 10.1038/ng.787.
6 Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
7 Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.Nat Genet. 2015 Apr;47(4):381-6. doi: 10.1038/ng.3245. Epub 2015 Mar 9.
8 Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.Nat Genet. 2014 Nov;46(11):1187-96. doi: 10.1038/ng.3118. Epub 2014 Oct 12.
9 Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
10 Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
11 HORMAD2 methylation-mediated epigenetic regulation of gene expression in thyroid cancer.J Cell Mol Med. 2018 Oct;22(10):4640-4652. doi: 10.1111/jcmm.13680. Epub 2018 Jul 24.
12 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.