Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5YLZIH)

DOT Name Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1)
Synonyms Voltage-gated calcium channel subunit alpha-2/delta-1
Gene Name CACNA2D1
Related Disease
Short QT syndrome ( )
Brugada syndrome ( )
Brugada syndrome 1 ( )
Developmental and epileptic encephalopathy 110 ( )
Infantile spasm ( )
UniProt ID
CA2D1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7MIX; 7MIY; 7UHF; 7UHG; 7VFS; 7VFU; 7VFV; 7VFW; 7XLQ; 7YG5; 8E59; 8E5A; 8E5B; 8EPL; 8EPM; 8IF3; 8IF4; 8WE6; 8WE7; 8WE8; 8WE9; 8WEA
Pfam ID
PF08473 ; PF00092 ; PF08399
Sequence
MAAGCLLALTLTLFQSLLIGPSSEEPFPSAVTIKSWVDKMQEDLVTLAKTASGVNQLVDI
YEKYQDLYTVEPNNARQLVEIAARDIEKLLSNRSKALVRLALEAEKVQAAHQWREDFASN
EVVYYNAKDDLDPEKNDSEPGSQRIKPVFIEDANFGRQISYQHAAVHIPTDIYEGSTIVL
NELNWTSALDEVFKKNREEDPSLLWQVFGSATGLARYYPASPWVDNSRTPNKIDLYDVRR
RPWYIQGAASPKDMLILVDVSGSVSGLTLKLIRTSVSEMLETLSDDDFVNVASFNSNAQD
VSCFQHLVQANVRNKKVLKDAVNNITAKGITDYKKGFSFAFEQLLNYNVSRANCNKIIML
FTDGGEERAQEIFNKYNKDKKVRVFTFSVGQHNYDRGPIQWMACENKGYYYEIPSIGAIR
INTQEYLDVLGRPMVLAGDKAKQVQWTNVYLDALELGLVITGTLPVFNITGQFENKTNLK
NQLILGVMGVDVSLEDIKRLTPRFTLCPNGYYFAIDPNGYVLLHPNLQPKPIGVGIPTIN
LRKRRPNIQNPKSQEPVTLDFLDAELENDIKVEIRNKMIDGESGEKTFRTLVKSQDERYI
DKGNRTYTWTPVNGTDYSLALVLPTYSFYYIKAKLEETITQARYSETLKPDNFEESGYTF
IAPRDYCNDLKISDNNTEFLLNFNEFIDRKTPNNPSCNADLINRVLLDAGFTNELVQNYW
SKQKNIKGVKARFVVTDGGITRVYPKEAGENWQENPETYEDSFYKRSLDNDNYVFTAPYF
NKSGPGAYESGIMVSKAVEIYIQGKLLKPAVVGIKIDVNSWIENFTKTSIRDPCAGPVCD
CKRNSDVMDCVILDDGGFLLMANHDDYTNQIGRFFGEIDPSLMRHLVNISVYAFNKSYDY
QSVCEPGAAPKQGAGHRSAYVPSVADILQIGWWATAAAWSILQQFLLSLTFPRLLEAVEM
EDDDFTASLSKQSCITEQTQYFFDNDSKSFSGVLDCGNCSRIFHGEKLMNTNLIFIMVES
KGTCPCDTRLLIQAEQTSDGPNPCDMVKQPRYRKGPDVCFDNNVLEDYTDCGGVSGLNPS
LWYIIGIQFLLLWLVSGSTHRLL
Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling.
Tissue Specificity
Isoform 1 is expressed in skeletal muscle. Isoform 2 is expressed in the central nervous system. Isoform 2, isoform 4 and isoform 5 are expressed in neuroblastoma cells. Isoform 3, isoform 4 and isoform 5 are expressed in the aorta.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Cardiac muscle contraction (hsa04260 )
Adrenergic sig.ling in cardiomyocytes (hsa04261 )
Oxytocin sig.ling pathway (hsa04921 )
Hypertrophic cardiomyopathy (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Dilated cardiomyopathy (hsa05414 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Short QT syndrome DISOI9X1 Supportive Autosomal dominant [1]
Brugada syndrome DISSGN0E Disputed Autosomal dominant [2]
Brugada syndrome 1 DISKBA7V Disputed Autosomal dominant [3]
Developmental and epileptic encephalopathy 110 DISBPXM2 Limited Autosomal recessive [4]
Infantile spasm DISZSKDG Limited Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [7]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [8]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [9]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [10]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [13]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [11]
OXYBENZONE DMMZYX6 Investigative OXYBENZONE increases the expression of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [15]
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⏷ Show the Full List of 11 Drug(s)
2 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 Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1). [14]
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References

1 Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J. 2011 May;32(9):1077-88. doi: 10.1093/eurheartj/ehr076. Epub 2011 Mar 7.
2 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3 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.
4 The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Nov 13;515(7526):216-21. doi: 10.1038/nature13908. Epub 2014 Oct 29.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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 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.
10 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
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 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.
13 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
14 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.
15 Chromatin modifiers: A new class of pollutants with potential epigenetic effects revealed by in vitro assays and transcriptomic analyses. Toxicology. 2023 Jan 15;484:153413. doi: 10.1016/j.tox.2022.153413. Epub 2022 Dec 26.