CAV3

caveolin 3, the group of Caveolins

Basic information

Region (hg38): 3:8733801-8841808

Links

ENSG00000182533 ∙ NCBI:859 ∙ OMIM:601253 ∙ HGNC:1529 ∙ Uniprot:P56539 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 1 (Limited), mode of inheritance: AD
• Brugada syndrome (Limited), mode of inheritance: AD
• rippling muscle disease 2 (Moderate), mode of inheritance: AD
• long QT syndrome 9 (Moderate), mode of inheritance: AD
• inherited rippling muscle disease (Supportive), mode of inheritance: AD
• distal myopathy, Tateyama type (Supportive), mode of inheritance: AD
• autosomal dominant limb-girdle muscular dystrophy type 1C (Strong), mode of inheritance: AR
• long QT syndrome 9 (Limited), mode of inheritance: AD
• long QT syndrome (Limited), mode of inheritance: AD
• caveolinopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic; Long QT syndrome 9; Creatine phosphokinase, elevated serum	AD/Digenic	Cardiovascular; Pharmacogenomic	Preventive measures and medical management may be helpful to help decrease morbidity related to cardiovascular manifestations; In individuals with isolated CK elevation, precautions should be taken during surgical/anesthetic procedures and anesthesia due to malignant hyperthermia risk	Cardiovascular; Musculoskeletal	2705900; 9536092; 9537420; 10220144; 10227634; 10746614; 11431690; 11251997; 11805270; 12939441; 12666119; 14672715; 15668980; 16247063; 17060380; 17275750; 20229577; 20301308; 20301559; 20809527; 22245016; 22581547
Conditions may involve digenic inheritance

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAV3 gene.

• Long QT syndrome (182 variants)
• not provided (149 variants)
• Cardiovascular phenotype (88 variants)
• not specified (63 variants)
• Caveolinopathy (53 variants)
• Limb-Girdle Muscular Dystrophy, Dominant (28 variants)
• Congenital long QT syndrome (26 variants)
• Cardiomyopathy (25 variants)
• Rippling muscle disease 2 (11 variants)
• Elevated circulating creatine kinase concentration (6 variants)
• Long QT syndrome 9 (5 variants)
• Long QT syndrome 1 (4 variants)
• CAV3-related condition (4 variants)
• Hypertrophic cardiomyopathy 1;Distal myopathy, Tateyama type;Elevated circulating creatine kinase concentration;Long QT syndrome 9;Rippling muscle disease 2 (3 variants)
• Elevated circulating creatine kinase concentration;Long QT syndrome 9;Distal myopathy, Tateyama type;Hypertrophic cardiomyopathy 1;Rippling muscle disease 2 (3 variants)
• Distal myopathy, Tateyama type;Elevated circulating creatine kinase concentration;Long QT syndrome 9;Rippling muscle disease 2;Hypertrophic cardiomyopathy 1 (3 variants)
• Limb-girdle muscular dystrophy (2 variants)
• Hypertrophic cardiomyopathy 1;Long QT syndrome 9;Distal myopathy, Tateyama type;Elevated circulating creatine kinase concentration;Rippling muscle disease 2 (2 variants)
• Distal myopathy, Tateyama type (2 variants)
• Tip-toe gait (1 variants)
• Hypertrophic cardiomyopathy 1;Distal myopathy, Tateyama type;Long QT syndrome 9;Rippling muscle disease 2;Elevated circulating creatine kinase concentration (1 variants)
• Elevated circulating creatine kinase concentration;Distal myopathy, Tateyama type;Hypertrophic cardiomyopathy 1;Long QT syndrome 9;Rippling muscle disease 2 (1 variants)
• Inborn genetic diseases (1 variants)
• See cases (1 variants)
• Rippling muscle disease 2;Long QT syndrome 9;Distal myopathy, Tateyama type;Elevated circulating creatine kinase concentration;Hypertrophic cardiomyopathy 1 (1 variants)
• Hypertrophic cardiomyopathy 1;Long QT syndrome 9;Elevated circulating creatine kinase concentration;Rippling muscle disease 2;Distal myopathy, Tateyama type (1 variants)
• Rippling muscle disease 2;Hypertrophic cardiomyopathy 1;Elevated circulating creatine kinase concentration;Long QT syndrome 9;Distal myopathy, Tateyama type (1 variants)
• Elevated circulating creatine kinase concentration;Hypertrophic cardiomyopathy 1;Rippling muscle disease 2;Distal myopathy, Tateyama type;Long QT syndrome 9 (1 variants)
• Hypertrophic cardiomyopathy 1;Elevated circulating creatine kinase concentration;Rippling muscle disease 2;Long QT syndrome 9;Distal myopathy, Tateyama type (1 variants)
• Abnormality of the musculature (1 variants)
• Distal myopathy, Tateyama type;Elevated circulating creatine kinase concentration;Rippling muscle disease 2;Long QT syndrome 9;Hypertrophic cardiomyopathy 1 (1 variants)
• SUDDEN INFANT DEATH SYNDROME (1 variants)
• Hypertrophic cardiomyopathy 1;Distal myopathy, Tateyama type;Long QT syndrome 9;Elevated circulating creatine kinase concentration;Rippling muscle disease 2 (1 variants)
• Long QT syndrome 9;Rippling muscle disease 2;Elevated circulating creatine kinase concentration;Hypertrophic cardiomyopathy 1;Distal myopathy, Tateyama type (1 variants)
• Hypertrophic cardiomyopathy 1;Distal myopathy, Tateyama type;Rippling muscle disease 2;Long QT syndrome 9;Elevated circulating creatine kinase concentration (1 variants)
• Long QT syndrome 9;Rippling muscle disease 2;Distal myopathy, Tateyama type;Hypertrophic cardiomyopathy 1;Elevated circulating creatine kinase concentration (1 variants)
• Rippling muscle disease 2, autosomal recessive (1 variants)
• Long QT syndrome 2/9, digenic (1 variants)
• Rippling muscle disease 2;Hypertrophic cardiomyopathy 1;Long QT syndrome 9;Elevated circulating creatine kinase concentration;Distal myopathy, Tateyama type (1 variants)
• Hypertrophic cardiomyopathy 1 (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• Hypertrophic cardiomyopathy 1;Long QT syndrome 9;Distal myopathy, Tateyama type;Rippling muscle disease 2;Elevated circulating creatine kinase concentration (1 variants)
• Distal myopathy, Tateyama type;Hypertrophic cardiomyopathy 1;Rippling muscle disease 2;Long QT syndrome 9;Elevated circulating creatine kinase concentration (1 variants)
• Rippling muscle disease 2;Distal myopathy, Tateyama type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAV3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				59		59
missense	5	6	112	2		125
nonsense	1	1	1			3
start loss						0
frameshift	1	2	1			4
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1		2			3
splice region			2	6		8
non coding			17	21	25	63
Total	8	9	139	82	25

Highest pathogenic variant AF is 0.00000658

Variants in CAV3

This is a list of pathogenic ClinVar variants found in the CAV3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-8733829-C-T		not specified	Likely benign (Jun 17, 2016)
3-8733830-C-T		not specified	Benign (Apr 28, 2015)
3-8733831-G-A			Benign (Mar 03, 2015)
3-8733840-G-A		not specified • Limb-Girdle Muscular Dystrophy, Dominant • Caveolinopathy • Congenital long QT syndrome • Tip-toe gait	Conflicting classifications of pathogenicity (Jan 12, 2018)
3-8733844-G-A		not specified	Likely benign (Apr 20, 2017)
3-8733844-G-T		not specified • Caveolinopathy • Limb-Girdle Muscular Dystrophy, Dominant • Congenital long QT syndrome	Conflicting classifications of pathogenicity (Jan 12, 2018)
3-8733846-A-G		CAV3-related disorder	Benign/Likely benign (Aug 26, 2022)
3-8733848-C-T		not specified	Likely benign (Apr 20, 2017)
3-8733862-C-A		not specified	Benign (May 18, 2014)
3-8733875-C-A			Likely benign (Aug 01, 2023)
3-8733875-C-T		not specified • Cardiomyopathy	Conflicting classifications of pathogenicity (Jul 26, 2017)
3-8733876-G-A		not specified • Cardiovascular phenotype	Benign/Likely benign (Jan 25, 2019)
3-8733881-T-C		Long QT syndrome	Uncertain significance (Jan 26, 2019)
3-8733881-TGG-T		Long QT syndrome • not specified • CAV3-related disorder	Conflicting classifications of pathogenicity (Sep 06, 2023)
3-8733882-GGCAGAAGA-G		Elevated circulating creatine kinase concentration • Long QT syndrome • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jun 11, 2023)
3-8733883-G-A		Long QT syndrome	Uncertain significance (May 03, 2022)
3-8733885-A-G		Long QT syndrome • Cardiovascular phenotype	Likely benign (Oct 24, 2020)
3-8733888-A-AG			not provided (-)
3-8733891-G-C			Uncertain significance (Dec 08, 2017)
3-8733893-A-G		Cardiovascular phenotype	Uncertain significance (Nov 12, 2021)
3-8733893-A-T		Long QT syndrome	Uncertain significance (Oct 22, 2022)
3-8733894-C-T		Cardiovascular phenotype	Likely benign (Jan 11, 2022)
3-8733895-A-G		Long QT syndrome	Uncertain significance (Sep 18, 2023)
3-8733898-G-A		Long QT syndrome 9	Uncertain significance (Mar 09, 2021)
3-8733903-C-G		Long QT syndrome	Likely benign (Jan 02, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAV3	protein_coding	protein_coding	ENST00000343849	2	108007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00546	0.730	125733	0	13	125746	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.830	69	91.3	0.756	0.00000555	990
Missense in Polyphen		28	38.217	0.73265		393
Synonymous	-0.580	45	40.3	1.12	0.00000265	288
Loss of Function	0.787	4	6.10	0.656	3.48e-7	60

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Mediates the recruitment of CAVIN2 and CAVIN3 proteins to the caveolae (PubMed:19262564). {ECO:0000250|UniProtKB:P51637, ECO:0000269|PubMed:19262564}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 1C (LGMD1C) [MIM:607801]: A degenerative myopathy characterized by calf hypertrophy and mild to moderate proximal muscle weakness. Inheritance can be autosomal dominant or recessive. {ECO:0000269|PubMed:11001938, ECO:0000269|PubMed:11532985, ECO:0000269|PubMed:12557291, ECO:0000269|PubMed:12939441, ECO:0000269|PubMed:15564037, ECO:0000269|PubMed:15580566, ECO:0000269|PubMed:9537420}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: HyperCKmia (HYPCK) [MIM:123320]: Characterized by persistent elevated levels of serum creatine kinase without muscle weakness. {ECO:0000269|PubMed:10746614, ECO:0000269|PubMed:12082049, ECO:0000269|PubMed:14663034, ECO:0000269|PubMed:15099591, ECO:0000269|PubMed:15580566}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Rippling muscle disease 2 (RMD2) [MIM:606072]: A disorder characterized by mechanically triggered contractions of skeletal muscle. Mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers and cause visible ripples to move over the muscle. RMD2 inheritance is autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:11431690, ECO:0000269|PubMed:11756609, ECO:0000269|PubMed:12557291, ECO:0000269|PubMed:12666119, ECO:0000269|PubMed:15668980, ECO:0000269|PubMed:16458928}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic (CMH) [MIM:192600]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:14672715}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Long QT syndrome 9 (LQT9) [MIM:611818]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:17060380, ECO:0000269|PubMed:17275750}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. {ECO:0000269|PubMed:17275750}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Myopathy, distal, Tateyama type (MPDT) [MIM:614321]: A disorder characterized by progressive muscular atrophy and muscle weakness beginning in the hands, the legs, or the feet. Muscle atrophy may be restricted to the small muscles of the hands and feet. {ECO:0000269|PubMed:11805270, ECO:0000269|PubMed:15580566}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);Endocytosis - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Integrin-mediated Cell Adhesion;Focal Adhesion;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Smooth Muscle Contraction;Muscle contraction;PDGFR-alpha signaling pathway (Consensus)

Recessive Scores

• pRec: 0.557

Intolerance Scores

• loftool: 0.0466
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.383
• hipred: Y
• hipred_score: 0.813
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.791

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cav3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: plasma membrane repair;regulation of heart rate;negative regulation of protein kinase activity;triglyceride metabolic process;endocytosis;muscle contraction;plasma membrane organization;actin filament organization;positive regulation of cytosolic calcium ion concentration;muscle organ development;myoblast fusion;regulation of heart contraction;protein localization;positive regulation of cell population proliferation;negative regulation of cardiac muscle hypertrophy;positive regulation of myotube differentiation;regulation of skeletal muscle contraction;regulation of transforming growth factor beta receptor signaling pathway;cell differentiation;positive regulation of microtubule polymerization;cytoplasmic microtubule organization;membrane raft organization;T-tubule organization;detection of muscle stretch;regulation of signal transduction by receptor internalization;regulation of membrane potential;glucose homeostasis;cholesterol homeostasis;negative regulation of MAP kinase activity;negative regulation of MAPK cascade;negative regulation of cell size;muscle cell cellular homeostasis;negative regulation of nitric-oxide synthase activity;regulation of nerve growth factor receptor activity;nucleus localization;regulation of protein kinase B signaling;negative regulation of calcium ion transport;cardiac muscle cell development;regulation of cardiac muscle contraction;negative regulation of sarcomere organization;regulation of ventricular cardiac muscle cell membrane repolarization;heart trabecula formation;regulation of ventricular cardiac muscle cell membrane depolarization;regulation of branching involved in mammary gland duct morphogenesis;negative regulation of cell growth involved in cardiac muscle cell development;caveola assembly;cellular response to organonitrogen compound;protein localization to plasma membrane;ventricular cardiac muscle cell action potential;regulation of calcium ion import;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of p38MAPK cascade;regulation of membrane depolarization during cardiac muscle cell action potential;negative regulation of membrane depolarization during cardiac muscle cell action potential;negative regulation of potassium ion transmembrane transporter activity;regulation of calcium ion transmembrane transporter activity;negative regulation of potassium ion transmembrane transport;negative regulation of protein localization to cell surface;positive regulation of ubiquitin-dependent protein catabolic process;regulation of sodium ion transmembrane transporter activity;positive regulation of caveolin-mediated endocytosis
• Cellular component: Golgi membrane;cytoplasm;endoplasmic reticulum;plasma membrane;integral component of plasma membrane;caveola;focal adhesion;cell surface;intercalated disc;dystrophin-associated glycoprotein complex;Z disc;T-tubule;neuromuscular junction;vesicle;protein-containing complex;sarcolemma;intracellular membrane-bounded organelle;membrane raft
• Molecular function: structural molecule activity;calcium channel regulator activity;protein binding;protein C-terminus binding;sodium channel regulator activity;potassium channel inhibitor activity;protein-containing complex scaffold activity;alpha-tubulin binding;ion channel binding;protein-containing complex binding;nitric-oxide synthase binding;connexin binding