Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCXYW4Y)

DOT Name Heart- and neural crest derivatives-expressed protein 2 (HAND2)
Synonyms Class A basic helix-loop-helix protein 26; bHLHa26; Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2; dHAND
Gene Name HAND2
Related Disease
Advanced cancer ( )
Cardiac failure ( )
Chromosomal disorder ( )
Colon cancer ( )
Colon carcinoma ( )
Congenital deformities of limbs ( )
Congestive heart failure ( )
Endometriosis ( )
Familial dilated cardiomyopathy ( )
Familial long QT syndrome ( )
Immunodeficiency ( )
Incontinentia pigmenti ( )
Melanoma ( )
Neoplasm ( )
Neuroblastoma ( )
Pulmonary disease ( )
Saethre-Chotzen syndrome ( )
Tooth agenesis ( )
Triple negative breast cancer ( )
X-linked hypohidrotic ectodermal dysplasia ( )
Atrial fibrillation ( )
Colorectal carcinoma ( )
Familial atrial fibrillation ( )
HAND2 related congenital heart defect ( )
Hirschsprung disease ( )
Tetralogy of fallot ( )
Obsolete familial isolated dilated cardiomyopathy ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Adenocarcinoma ( )
Cardiomyopathy ( )
Cleft palate ( )
Congenital heart disease ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Dilated cardiomyopathy 1A ( )
Isolated cleft palate ( )
Squamous cell carcinoma ( )
UniProt ID
HAND2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00010
Sequence
MSLVGGFPHHPVVHHEGYPFAAAAAAAAAAAASRCSHEENPYFHGWLIGHPEMSPPDYSM
ALSYSPEYASGAAGLDHSHYGGVPPGAGPPGLGGPRPVKRRGTANRKERRRTQSINSAFA
ELRECIPNVPADTKLSKIKTLRLATSYIAYLMDLLAKDDQNGEAEAFKAEIKKTDVKEEK
RKKELNEILKSTVSSNDKKTKGRTGWPQHVWALELKQ
Function
Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries. Required for vascular development and regulation of angiogenesis, possibly through a VEGF signaling pathway. Also plays an important role in limb development, particularly in the establishment of anterior-posterior polarization, acting as an upstream regulator of sonic hedgehog (SHH) induction in the limb bud. Is involved in the development of branchial arches, which give rise to unique structures in the head and neck. Binds DNA on E-box consensus sequence 5'-CANNTG-3'.
Tissue Specificity Heart.
Reactome Pathway
Cardiogenesis (R-HSA-9733709 )
Transcriptional regulation by RUNX2 (R-HSA-8878166 )

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Cardiac failure DISDC067 Strong Biomarker [2]
Chromosomal disorder DISM5BB5 Strong Biomarker [3]
Colon cancer DISVC52G Strong Biomarker [4]
Colon carcinoma DISJYKUO Strong Biomarker [4]
Congenital deformities of limbs DISP4N1Q Strong Altered Expression [5]
Congestive heart failure DIS32MEA Strong Biomarker [2]
Endometriosis DISX1AG8 Strong Biomarker [6]
Familial dilated cardiomyopathy DISBHDU9 Strong Genetic Variation [7]
Familial long QT syndrome DISRNNCY Strong Biomarker [8]
Immunodeficiency DIS093I0 Strong Genetic Variation [9]
Incontinentia pigmenti DIS0ALLE Strong Biomarker [10]
Melanoma DIS1RRCY Strong Biomarker [1]
Neoplasm DISZKGEW Strong Biomarker [11]
Neuroblastoma DISVZBI4 Strong Biomarker [12]
Pulmonary disease DIS6060I Strong Biomarker [13]
Saethre-Chotzen syndrome DIS3A437 Strong Biomarker [14]
Tooth agenesis DIS1PWC7 Strong Biomarker [15]
Triple negative breast cancer DISAMG6N Strong Altered Expression [16]
X-linked hypohidrotic ectodermal dysplasia DISST0XM Strong Genetic Variation [9]
Atrial fibrillation DIS15W6U moderate Genetic Variation [17]
Colorectal carcinoma DIS5PYL0 moderate Biomarker [18]
Familial atrial fibrillation DISL4AGF moderate Biomarker [17]
HAND2 related congenital heart defect DISERMKS Moderate Autosomal dominant [19]
Hirschsprung disease DISUUSM1 moderate Biomarker [20]
Tetralogy of fallot DISMHFNW moderate Genetic Variation [21]
Obsolete familial isolated dilated cardiomyopathy DIS4FXO4 Supportive Autosomal dominant [7]
Endometrial cancer DISW0LMR Disputed Biomarker [22]
Endometrial carcinoma DISXR5CY Disputed Biomarker [22]
Adenocarcinoma DIS3IHTY Limited Altered Expression [23]
Cardiomyopathy DISUPZRG Limited Altered Expression [24]
Cleft palate DIS6G5TF Limited Genetic Variation [25]
Congenital heart disease DISQBA23 Limited Biomarker [21]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [26]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [26]
Dilated cardiomyopathy 1A DIS0RK9Z Limited Biomarker [7]
Isolated cleft palate DISV80CD Limited Genetic Variation [25]
Squamous cell carcinoma DISQVIFL Limited Altered Expression [23]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [27]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [28]
Progesterone DMUY35B Approved Progesterone increases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [29]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [30]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [31]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [32]
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⏷ Show the Full List of 6 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Heart- and neural crest derivatives-expressed protein 2 (HAND2). [33]
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References

1 LncRNA HAND2-AS1 overexpression inhibits cancer cell proliferation in melanoma by downregulating ROCK1.Oncol Lett. 2019 Aug;18(2):1005-1010. doi: 10.3892/ol.2019.10402. Epub 2019 May 27.
2 A context-specific cardiac -catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart.Nucleic Acids Res. 2018 Apr 6;46(6):2850-2867. doi: 10.1093/nar/gky049.
3 Overdosage of Hand2 causes limb and heart defects in the human chromosomal disorder partial trisomy distal 4q.Hum Mol Genet. 2013 Jun 15;22(12):2471-81. doi: 10.1093/hmg/ddt099. Epub 2013 Feb 27.
4 Identification of regulatory role of DNA methylation in colon cancer gene expression via systematic bioinformatics analysis.Medicine (Baltimore). 2017 Nov;96(47):e8487. doi: 10.1097/MD.0000000000008487.
5 The Hand2 gene dosage effect in developmental defects and human congenital disorders.Curr Top Dev Biol. 2014;110:129-52. doi: 10.1016/B978-0-12-405943-6.00003-8.
6 Upregulation of Fibroblast Growth Factors Caused by Heart and Neural Crest Derivatives Expressed 2 Suppression in Endometriotic Cells: A Possible Therapeutic Target in Endometriosis.Reprod Sci. 2019 Jul;26(7):979-987. doi: 10.1177/1933719118802053. Epub 2018 Oct 1.
7 HAND2 loss-of-function mutation causes familial dilated cardiomyopathy. Eur J Med Genet. 2019 Sep;62(9):103540. doi: 10.1016/j.ejmg.2018.09.007. Epub 2018 Sep 12.
8 Cardiac retention of [11C]HED in genotyped long QT patients: a potential amplifier role for severity of the disease.Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1286-93. doi: 10.1152/ajpheart.00276.2003. Epub 2003 May 29.
9 BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.Acta Neuropathol Commun. 2016 Jul 13;4(1):73. doi: 10.1186/s40478-016-0342-3.
10 Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.Pediatr Dermatol. 2014 Nov-Dec;31(6):716-21. doi: 10.1111/pde.12103. Epub 2013 Feb 14.
11 Giant Olfactory Groove Meningioma-2-Staged Approach: 2-Dimensional Operative Video.Oper Neurosurg (Hagerstown). 2019 Jan 1;16(1):115-116. doi: 10.1093/ons/opy092.
12 Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry.Nat Genet. 2018 Sep;50(9):1240-1246. doi: 10.1038/s41588-018-0191-z. Epub 2018 Aug 20.
13 Silencing of heart and neural crest derivatives expressed transcript 2 attenuates transforming growth factor-1-enhanced apoptosis of human bronchial epithelial cells.Oncol Lett. 2018 Oct;16(4):4997-5005. doi: 10.3892/ol.2018.9299. Epub 2018 Aug 13.
14 Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities.Nat Genet. 2005 Apr;37(4):373-81. doi: 10.1038/ng1525. Epub 2005 Feb 27.
15 Dento-maxillo-facial phenotype and implants-based oral rehabilitation in Ectodermal Dysplasia with WNT10A gene mutation: report of a case and literature review.J Craniomaxillofac Surg. 2014 Sep;42(6):e346-51. doi: 10.1016/j.jcms.2014.01.037. Epub 2014 Jan 15.
16 Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 overexpression inhibits the proliferation of cancer cells by reducing RUNX2 expression in triple-negative breast cancer.Oncol Lett. 2019 Dec;18(6):6775-6780. doi: 10.3892/ol.2019.11001. Epub 2019 Oct 18.
17 Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
18 LncRNA HAND2-AS1 inhibits 5-fluorouracil resistance by modulating miR-20a/PDCD4 axis in colorectal cancer.Cell Signal. 2020 Feb;66:109483. doi: 10.1016/j.cellsig.2019.109483. Epub 2019 Nov 21.
19 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
20 The research on screening differentially expressed genes in Hirschsprung's disease by using Microarray.J Pediatr Surg. 2013 Nov;48(11):2281-8. doi: 10.1016/j.jpedsurg.2013.06.024.
21 A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot.Int J Mol Med. 2016 Feb;37(2):445-51. doi: 10.3892/ijmm.2015.2436. Epub 2015 Dec 15.
22 Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings.Clin Epigenetics. 2019 Nov 28;11(1):170. doi: 10.1186/s13148-019-0765-3.
23 Expression analysis of angiogenesis-related genes in Bulgarian patients with early-stage non-small cell lung cancer.Tumori. 2011 Jan-Feb;97(1):86-94. doi: 10.1177/030089161109700116.
24 Human eHAND, but not dHAND, is down-regulated in cardiomyopathies.J Mol Cell Cardiol. 2001 Sep;33(9):1607-14. doi: 10.1006/jmcc.2001.1434.
25 Requirement of Hyaluronan Synthase-2 in Craniofacial and Palate Development.J Dent Res. 2019 Nov;98(12):1367-1375. doi: 10.1177/0022034519872478. Epub 2019 Sep 11.
26 A HAND to TBX5 Explains the Link Between Thalidomide and Cardiac Diseases.Sci Rep. 2017 May 3;7(1):1416. doi: 10.1038/s41598-017-01641-3.
27 Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
28 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
29 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
30 Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
31 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
32 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
33 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.