Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSFDB4)

DOT Name Caveolin-3 (CAV3)
Synonyms M-caveolin
Gene Name CAV3
Related Disease
Caveolinopathy ( )
Distal myopathy ( )
Hyperglycemia ( )
Type-1/2 diabetes ( )
Absence epilepsy ( )
Acute lymphocytic leukaemia ( )
Arrhythmia ( )
Atrial fibrillation ( )
Benign prostatic hyperplasia ( )
Breast neoplasm ( )
Cardiac disease ( )
Cardiac failure ( )
Cardiomyopathy ( )
Cardiovascular disease ( )
Childhood acute lymphoblastic leukemia ( )
Congestive heart failure ( )
Dilated cardiomyopathy 1A ( )
Duchenne muscular dystrophy ( )
Familial hypertrophic cardiomyopathy ( )
Familial long QT syndrome ( )
Hepatitis C virus infection ( )
High blood pressure ( )
Hypertrophic cardiomyopathy ( )
Limb-girdle muscular dystrophy ( )
Lymphoma, non-Hodgkin, familial ( )
Myasthenia gravis ( )
Myocardial infarction ( )
Myopathy ( )
Neoplasm ( )
Neuralgia ( )
Non-hodgkin lymphoma ( )
Non-insulin dependent diabetes ( )
Obsolete autosomal dominant limb-girdle muscular dystrophy type 1C ( )
Osteoporosis ( )
Vibrio cholerae infection ( )
Long QT syndrome 9 ( )
Rhabdomyosarcoma ( )
Rippling muscle disease 2 ( )
Distal myopathy, Tateyama type ( )
Inherited rippling muscle disease ( )
Rippling muscle disease ( )
Brugada syndrome ( )
GNE myopathy ( )
Hypertrophic cardiomyopathy 1 ( )
Intellectual disability ( )
Long QT syndrome ( )
Muscular dystrophy ( )
Peripheral neuropathy ( )
UniProt ID
CAV3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF01146
Sequence
MMAEEHTDLEAQIVKDIHCKEIDLVNRDPKNINEDIVKVDFEDVIAEPVGTYSFDGVWKV
SYTTFTVSKYWCYRLLSTLLGVPLALLWGFLFACISFCHIWAVVPCIKSYLIEIQCISHI
YSLCIRTFCNPLFAALGQVCSSIKVVLRKEV
Function
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium channels. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress. Mediates the recruitment of CAVIN2 and CAVIN3 proteins to the caveolae.
Tissue Specificity Expressed predominantly in muscle.
KEGG Pathway
Endocytosis (hsa04144 )
Focal adhesion (hsa04510 )
Prion disease (hsa05020 )
Bacterial invasion of epithelial cells (hsa05100 )
Proteoglycans in cancer (hsa05205 )
Hypertrophic cardiomyopathy (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Dilated cardiomyopathy (hsa05414 )
Viral myocarditis (hsa05416 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Smooth Muscle Contraction (R-HSA-445355 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Caveolinopathy DISLVYBG Definitive Autosomal dominant [1]
Distal myopathy DIS7F5R0 Definitive Genetic Variation [2]
Hyperglycemia DIS0BZB5 Definitive Altered Expression [3]
Type-1/2 diabetes DISIUHAP Definitive Altered Expression [3]
Absence epilepsy DISJPOUD Strong Biomarker [4]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [5]
Arrhythmia DISFF2NI Strong Biomarker [6]
Atrial fibrillation DIS15W6U Strong Altered Expression [7]
Benign prostatic hyperplasia DISI3CW2 Strong Altered Expression [8]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Cardiac disease DISVO1I5 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Altered Expression [11]
Cardiomyopathy DISUPZRG Strong Genetic Variation [2]
Cardiovascular disease DIS2IQDX Strong Biomarker [12]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Altered Expression [5]
Congestive heart failure DIS32MEA Strong Altered Expression [11]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Genetic Variation [13]
Duchenne muscular dystrophy DISRQ3NV Strong Altered Expression [14]
Familial hypertrophic cardiomyopathy DISQ89HN Strong Genetic Variation [13]
Familial long QT syndrome DISRNNCY Strong Genetic Variation [15]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [16]
High blood pressure DISY2OHH Strong Altered Expression [7]
Hypertrophic cardiomyopathy DISQG2AI Strong Genetic Variation [17]
Limb-girdle muscular dystrophy DISI9Y1Z Strong Genetic Variation [2]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Altered Expression [5]
Myasthenia gravis DISELRCI Strong Altered Expression [18]
Myocardial infarction DIS655KI Strong Altered Expression [10]
Myopathy DISOWG27 Strong Genetic Variation [19]
Neoplasm DISZKGEW Strong Altered Expression [20]
Neuralgia DISWO58J Strong Biomarker [4]
Non-hodgkin lymphoma DISS2Y8A Strong Altered Expression [5]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [21]
Obsolete autosomal dominant limb-girdle muscular dystrophy type 1C DISDUBBY Strong Autosomal recessive [22]
Osteoporosis DISF2JE0 Strong Altered Expression [23]
Vibrio cholerae infection DISW7E3U Strong Biomarker [24]
Long QT syndrome 9 DISZ5RC4 Moderate Autosomal dominant [25]
Rhabdomyosarcoma DISNR7MS moderate Biomarker [20]
Rippling muscle disease 2 DISVFPSL Moderate Autosomal dominant [25]
Distal myopathy, Tateyama type DISQIXBQ Supportive Autosomal dominant [26]
Inherited rippling muscle disease DISURBY5 Supportive Autosomal dominant [27]
Rippling muscle disease DISKW2XB Disputed Biomarker [28]
Brugada syndrome DISSGN0E Limited Autosomal dominant [29]
GNE myopathy DIS73X4W Limited Biomarker [30]
Hypertrophic cardiomyopathy 1 DISFOPCJ Limited Autosomal dominant [13]
Intellectual disability DISMBNXP Limited Genetic Variation [31]
Long QT syndrome DISMKWS3 Limited Autosomal dominant [1]
Muscular dystrophy DISJD6P7 Limited Genetic Variation [32]
Peripheral neuropathy DIS7KN5G Limited Biomarker [33]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Phenylephrine DMZHUO5 Approved Caveolin-3 (CAV3) decreases the response to substance of Phenylephrine. [38]
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This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
ANW-32821 DMMJOZD Phase 2 Caveolin-3 (CAV3) affects the import of ANW-32821. [39]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Caveolin-3 (CAV3). [34]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Caveolin-3 (CAV3). [35]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Caveolin-3 (CAV3). [36]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Caveolin-3 (CAV3). [37]
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References

1 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.
2 Mutation in the caveolin-3 gene causes asymmetrical distal myopathy.Neuropathology. 2016 Oct;36(5):485-489. doi: 10.1111/neup.12297. Epub 2016 Mar 7.
3 Hyperglycemia-Induced Oxidative Stress Abrogates Remifentanil Preconditioning-Mediated Cardioprotection in Diabetic Rats by Impairing Caveolin-3-Modulated PI3K/Akt and JAK2/STAT3 Signaling.Oxid Med Cell Longev. 2019 Sep 5;2019:9836302. doi: 10.1155/2019/9836302. eCollection 2019.
4 Cdk5-Dependent Phosphorylation of Ca(V)3.2 T-Type Channels: Possible Role in Nerve Ligation-Induced Neuropathic Allodynia and the Compound Action Potential in Primary Afferent C Fibers.J Neurosci. 2020 Jan 8;40(2):283-296. doi: 10.1523/JNEUROSCI.0181-19.2019. Epub 2019 Nov 19.
5 Deletion of 6q16-q21 in human lymphoid malignancies: a mapping and deletion analysis.Cancer Res. 2000 Jun 1;60(11):2775-9.
6 Caveolin-3 Microdomain: Arrhythmia Implications for Potassium Inward Rectifier and Cardiac Sodium Channel.Front Physiol. 2018 Nov 9;9:1548. doi: 10.3389/fphys.2018.01548. eCollection 2018.
7 Caveolae-Mediated Activation of Mechanosensitive Chloride Channels in Pulmonary Veins Triggers Atrial Arrhythmogenesis.J Am Heart Assoc. 2019 Oct 15;8(20):e012748. doi: 10.1161/JAHA.119.012748. Epub 2019 Oct 10.
8 NF-B and GATA-Binding Factor 6 Repress Transcription of Caveolins in Bladder Smooth Muscle Hypertrophy.Am J Pathol. 2019 Apr;189(4):847-867. doi: 10.1016/j.ajpath.2018.12.013. Epub 2019 Jan 30.
9 Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation.Am J Pathol. 2009 Feb;174(2):613-29. doi: 10.2353/ajpath.2009.080653.
10 Abnormal Downregulation of Caveolin-3 Mediates the Pro-Fibrotic Action of MicroRNA-22 in a Model of Myocardial Infarction.Cell Physiol Biochem. 2018;45(4):1641-1653. doi: 10.1159/000487732. Epub 2018 Feb 21.
11 Cardiac-specific overexpression of caveolin-3 preserves t-tubular I(Ca) during heart failure in mice.Exp Physiol. 2019 May;104(5):654-666. doi: 10.1113/EP087304. Epub 2019 Mar 14.
12 Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin.J Biol Chem. 2009 Jun 5;284(23):15894-902. doi: 10.1074/jbc.M109.009589. Epub 2009 Apr 20.
13 Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2004 Jan 2;313(1):178-84. doi: 10.1016/j.bbrc.2003.11.101.
14 Transgenic overexpression of caveolin-3 in the heart induces a cardiomyopathic phenotype.Hum Mol Genet. 2003 Nov 1;12(21):2777-88. doi: 10.1093/hmg/ddg313. Epub 2003 Sep 9.
15 Long QT syndrome caveolin-3 mutations differentially modulate K(v) 4 and Ca(v) 1.2 channels to contribute to action potential prolongation.J Physiol. 2019 Mar;597(6):1531-1551. doi: 10.1113/JP276014. Epub 2019 Jan 24.
16 A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus-coinfected patients.Hepatology. 2016 Nov;64(5):1462-1472. doi: 10.1002/hep.28695. Epub 2016 Jul 29.
17 Caveolinopathies: translational implications of caveolin-3 in skeletal and cardiac muscle disorders.Handb Clin Neurol. 2011;101:135-42. doi: 10.1016/B978-0-08-045031-5.00010-4.
18 Caveolin-3 is aberrantly expressed in skeletal muscle cells in myasthenia gravis.J Neuroimmunol. 2016 Dec 15;301:30-34. doi: 10.1016/j.jneuroim.2016.10.011. Epub 2016 Nov 9.
19 Coexistence of a CAV3 mutation and a DMD deletion in a family with complex muscular diseases.Brain Dev. 2019 May;41(5):474-479. doi: 10.1016/j.braindev.2019.01.005. Epub 2019 Feb 2.
20 MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.PLoS One. 2015 Jun 18;10(6):e0130287. doi: 10.1371/journal.pone.0130287. eCollection 2015.
21 Effect of type 2 diabetes mellitus caveolin-3 K15N mutation on glycometabolism.Exp Ther Med. 2019 Oct;18(4):2531-2539. doi: 10.3892/etm.2019.7840. Epub 2019 Aug 2.
22 Mutations in the caveolin-3 gene: When are they pathogenic?. Am J Med Genet. 2001 Apr 1;99(4):303-7. doi: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1168>3.0.co;2-o.
23 Overexpression of CAV3 facilitates bone formation via the Wnt signaling pathway in osteoporotic rats.Endocrine. 2019 Mar;63(3):639-650. doi: 10.1007/s12020-018-1803-1. Epub 2018 Nov 14.
24 Expression of caveolar components in primary desminopathy.Neuromuscul Disord. 2008 Mar;18(3):215-9. doi: 10.1016/j.nmd.2007.12.006. Epub 2008 Mar 14.
25 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.
26 Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy. Neurology. 2002 Jan 22;58(2):323-5. doi: 10.1212/wnl.58.2.323.
27 Consequences of a novel caveolin-3 mutation in a large German family. Ann Neurol. 2003 Feb;53(2):233-41. doi: 10.1002/ana.10442.
28 229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017.Neuromuscul Disord. 2018 Aug;28(8):702-710. doi: 10.1016/j.nmd.2018.05.007. Epub 2018 May 24.
29 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
30 Quantification of lectin fluorescence in GNE myopathy muscle biopsies.Muscle Nerve. 2018 Aug;58(2):286-292. doi: 10.1002/mus.26135. Epub 2018 Apr 23.
31 Molecular characterization and clinical features of a patient with an interstitial deletion of 3p25.3-p26.1.Am J Med Genet A. 2010 Dec;152A(12):3110-4. doi: 10.1002/ajmg.a.33353.
32 Characteristic findings of skeletal muscle MRI in caveolinopathies.Neuromuscul Disord. 2018 Oct;28(10):857-862. doi: 10.1016/j.nmd.2018.07.010. Epub 2018 Jul 31.
33 Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Physalin F via Block of CaV2.3 (R-Type) and CaV2.2 (N-Type) Voltage-Gated Calcium Channels.ACS Chem Neurosci. 2019 Jun 19;10(6):2939-2955. doi: 10.1021/acschemneuro.9b00166. Epub 2019 Apr 18.
34 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.
35 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
36 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
37 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.
38 Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy. Hypertension. 2003 Aug;42(2):213-9. doi: 10.1161/01.HYP.0000082926.08268.5D. Epub 2003 Jul 7.
39 High levels of caveolar cholesterol inhibit progesterone-induced genomic actions in human and guinea pig gallbladder muscle. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G948-54. doi: 10.1152/ajpgi.90699.2008. Epub 2009 Feb 12.