CAV1

caveolin 1, the group of Caveolins

Basic information

Region (hg38): 7:116524993-116561179

Previous symbols: [ "CAV" ]

Links

ENSG00000105974 ∙ NCBI:857 ∙ OMIM:601047 ∙ HGNC:1527 ∙ Uniprot:Q03135 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital generalized lipodystrophy type 3 (Limited), mode of inheritance: AR
• congenital generalized lipodystrophy type 3 (Moderate), mode of inheritance: AD
• pulmonary hypertension, primary, 3 (Limited), mode of inheritance: AD
• Berardinelli-Seip congenital lipodystrophy (Supportive), mode of inheritance: AR
• heritable pulmonary arterial hypertension (Supportive), mode of inheritance: AD
• partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (Strong), mode of inheritance: AD
• pulmonary hypertension, primary, 3 (Strong), mode of inheritance: AD
• pulmonary arterial hypertension (Definitive), mode of inheritance: AD
• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary hypertension, primary 3; Lipodystrophy, familial partial, type 7; Lipodystrophy, congenital generalized, type 3	AD/AR	Cardiovascular; Endocrine; Gastrointestinal; Pulmonary	Individuals with Pulmonary hypertension, primary, may manifest at variable ages, and awareness may allow surveillance, diagnosis of sequelae, and prompt management of disease; In Lipodystrophy, congenital generalized and Lipodystrophy, familial partial, dietary measures and medications may be beneficial; Surveillance for manifestations, including diabetes and abnormal lipid balance may allow early diagnosis and treatment	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	15028826; 18211975; 18237401; 21865368; 22474227

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CAV1 gene.

• Pulmonary hypertension, primary, 3 (46 variants)
• Inborn genetic diseases (44 variants)
• not provided (27 variants)
• Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (5 variants)
• not specified (3 variants)
• Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome;Congenital generalized lipodystrophy type 3;Pulmonary hypertension, primary, 3 (3 variants)
• Pulmonary hypertension, primary, 3;Congenital generalized lipodystrophy type 3;Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (3 variants)
• Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome;Pulmonary hypertension, primary, 3;Congenital generalized lipodystrophy type 3 (2 variants)
• Monogenic diabetes (2 variants)
• Congenital generalized lipodystrophy type 3 (2 variants)
• Pulmonary hypertension, primary, 3;Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (2 variants)
• Congenital generalized lipodystrophy type 3;Pulmonary hypertension, primary, 3 (1 variants)
• Congenital generalized lipodystrophy type 3;Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome;Pulmonary hypertension, primary, 3 (1 variants)
• CAV1-related condition (1 variants)
• Pulmonary hypertension, primary, 3;Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome;Congenital generalized lipodystrophy type 3 (1 variants)
• Pulmonary arterial hypertension associated with congenital heart disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAV1 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			1	25		26
missense			26	9		35
nonsense	1		1	1		3
start loss						0
frameshift	3	2				5
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			1	10	12	23
Total	4	2	29	45	12

Highest pathogenic variant AF is 0.00000657

Variants in CAV1

This is a list of pathogenic ClinVar variants found in the CAV1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-116525071-G-A		Inborn genetic diseases	Likely benign (Jan 29, 2024)
7-116525074-C-A		Pulmonary hypertension, primary, 3	Likely benign (May 17, 2021)
7-116525087-T-G		Inborn genetic diseases	Uncertain significance (Feb 11, 2022)
7-116525090-G-T		Pulmonary hypertension, primary, 3 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 06, 2022)
7-116525092-G-C		Pulmonary hypertension, primary, 3	Uncertain significance (Jul 17, 2020)
7-116525104-TG-T		Pulmonary hypertension, primary, 3	Benign (Dec 01, 2023)
7-116525104-T-TG		not specified • Pulmonary hypertension, primary, 3	Benign (Jan 31, 2024)
7-116525105-G-A		Pulmonary hypertension, primary, 3	Likely benign (Apr 28, 2023)
7-116525105-G-C		Pulmonary hypertension, primary, 3	Benign (Nov 13, 2023)
7-116525105-G-T		Pulmonary hypertension, primary, 3	Benign (Jan 11, 2024)
7-116525106-G-T		not specified • Pulmonary hypertension, primary, 3	Benign (Jan 30, 2024)
7-116525107-G-C		Pulmonary hypertension, primary, 3	Likely benign (Oct 30, 2023)
7-116525107-G-T		Pulmonary hypertension, primary, 3	Likely benign (Aug 16, 2023)
7-116525108-G-A		Pulmonary hypertension, primary, 3	Benign/Likely benign (Jan 30, 2024)
7-116525111-G-A		Pulmonary hypertension, primary, 3	Likely benign (Nov 24, 2023)
7-116525112-C-T		Pulmonary hypertension, primary, 3 • Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome;Congenital generalized lipodystrophy type 3;Pulmonary hypertension, primary, 3	Benign (Dec 08, 2023)
7-116525120-C-T			Likely benign (Mar 29, 2019)
7-116525179-C-T			Benign (Jul 06, 2018)
7-116525306-A-C		Congenital generalized lipodystrophy type 3 • Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome • Pulmonary hypertension, primary, 3	Benign (Jul 14, 2021)
7-116525409-T-C			Benign (Jun 14, 2018)
7-116526020-G-A			Benign (Jun 26, 2018)
7-116526072-C-CCGGGGA			Benign (Jun 26, 2018)
7-116526269-GC-G		Pulmonary hypertension, primary, 3	Likely benign (Nov 19, 2022)
7-116526317-TCTGC-T			Likely benign (Jul 07, 2018)
7-116526346-C-T			Benign (Jul 30, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAV1	protein_coding	protein_coding	ENST00000341049	3	36395

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00827	0.807	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.669	86	105	0.817	0.00000578	1194
Missense in Polyphen		30	39.207	0.76516		396
Synonymous	0.814	32	38.4	0.833	0.00000222	329
Loss of Function	1.03	4	6.94	0.576	2.99e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00228	0.00228
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)- mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3- dependent manner. Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway. Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (PubMed:25893292). Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (PubMed:19262564). {ECO:0000250|UniProtKB:P49817, ECO:0000269|PubMed:11751885, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:19262564, ECO:0000269|PubMed:25893292}.
• Disease: DISEASE: Congenital generalized lipodystrophy 3 (CGL3) [MIM:612526]: An autosomal recessive disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. {ECO:0000269|PubMed:18211975}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pulmonary hypertension, primary, 3 (PPH3) [MIM:615343]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269|PubMed:22474227}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome (LCCNS) [MIM:606721]: A form of familial partial lipodystrophy associated with congenital cataracts and neurodegeneration leading to cerebellar and spinal cord dysfunction. {ECO:0000269|PubMed:18237401}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);Viral myocarditis - 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);Androgen receptor signaling pathway;Integrin-mediated Cell Adhesion;Focal Adhesion;TGF-beta Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;EGF-EGFR Signaling Pathway;Signal Transduction;integrin signaling pathway;corticosteroids and cardioprotection;ion channels and their functional role in vascular endothelium;vegf hypoxia and angiogenesis;VEGFA-VEGFR2 Pathway;Metabolism of lipids;Metabolism of nitric oxide;eNOS activation;NOSTRIN mediated eNOS trafficking;eNOS activation and regulation;Metabolism;AndrogenReceptor;actions of nitric oxide in the heart;Integrin;TGF_beta_Receptor;Triglyceride catabolism;Triglyceride metabolism;EGFR1;Cell surface interactions at the vascular wall;Hemostasis;Signaling by VEGF;Direct p53 effectors;Basigin interactions;TNFalpha;Signaling by Receptor Tyrosine Kinases;Insulin Pathway;ALK1 signaling events;TNF receptor signaling pathway ;Canonical Wnt signaling pathway;Signaling events mediated by PTP1B;Signaling events mediated by VEGFR1 and VEGFR2;PDGFR-alpha signaling pathway;TGF-beta receptor signaling;VEGFR1 specific signals;VEGFR2 mediated vascular permeability (Consensus)

Recessive Scores

• pRec: 0.863

Intolerance Scores

• loftool: 0.0663
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.487
• hipred: Y
• hipred_score: 0.769
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.793

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cav1
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; digestive/alimentary phenotype; neoplasm; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); hematopoietic system phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: cav1
• Affected structure: muscle cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;inactivation of MAPK activity;angiogenesis;vasculogenesis;response to hypoxia;negative regulation of endothelial cell proliferation;negative regulation of cytokine-mediated signaling pathway;response to ischemia;regulation of the force of heart contraction by chemical signal;triglyceride metabolic process;calcium ion transport;cellular calcium ion homeostasis;regulation of smooth muscle contraction;skeletal muscle tissue development;lactation;protein localization;response to bacterium;positive regulation of calcium ion transport into cytosol;posttranscriptional regulation of gene expression;positive regulation of gene expression;positive regulation of peptidase activity;vesicle organization;receptor-mediated endocytosis of virus by host cell;regulation of fatty acid metabolic process;lipid storage;cell differentiation;regulation of blood coagulation;cholesterol transport;positive regulation of cell migration;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of epithelial cell differentiation;mammary gland development;T cell costimulation;negative regulation of protein ubiquitination;positive regulation of protein ubiquitination;receptor internalization;negative regulation of protein binding;positive regulation of protein binding;maintenance of protein location in cell;response to progesterone;negative regulation of peptidyl-serine phosphorylation;positive regulation of peptidyl-serine phosphorylation;nitric oxide homeostasis;positive regulation of toll-like receptor 3 signaling pathway;vasoconstriction;negative regulation of tyrosine phosphorylation of STAT protein;cholesterol homeostasis;positive regulation of catalytic activity;negative regulation of MAPK cascade;response to estrogen;protein localization to plasma membrane raft;negative regulation of nitric oxide biosynthetic process;positive regulation of vasoconstriction;negative regulation of JAK-STAT cascade;negative regulation of pinocytosis;leukocyte migration;regulation of nitric-oxide synthase activity;negative regulation of nitric-oxide synthase activity;protein homooligomerization;regulation of cytosolic calcium ion concentration;response to calcium ion;membrane depolarization;regulation of peptidase activity;calcium ion homeostasis;mammary gland involution;positive regulation of cell adhesion molecule production;negative regulation of necroptotic process;negative regulation of protein tyrosine kinase activity;caveola assembly;cellular response to exogenous dsRNA;cellular response to peptide hormone stimulus;cellular response to hyperoxia;cellular response to transforming growth factor beta stimulus;caveolin-mediated endocytosis;regulation of heart rate by cardiac conduction;angiotensin-activated signaling pathway involved in heart process;negative regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;apoptotic signaling pathway;regulation of membrane repolarization during action potential;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of ventricular cardiac muscle cell action potential;positive regulation of cold-induced thermogenesis;regulation of ruffle assembly;negative regulation of peptidyl-tyrosine autophosphorylation;negative regulation of potassium ion transmembrane transport;regulation of cell communication by electrical coupling involved in cardiac conduction;positive regulation of ER-associated ubiquitin-dependent protein catabolic process;protein localization to basolateral plasma membrane;positive regulation of gap junction assembly;negative regulation of inward rectifier potassium channel activity;beta-catenin destruction complex disassembly;receptor internalization involved in canonical Wnt signaling pathway;regulation of entry of bacterium into host cell;negative regulation of anoikis;positive regulation of extrinsic apoptotic signaling pathway;positive regulation of intrinsic apoptotic signaling pathway
• Cellular component: Golgi membrane;acrosomal membrane;cytoplasm;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;lipid droplet;plasma membrane;integral component of plasma membrane;caveola;focal adhesion;cilium;cell cortex;membrane;endocytic vesicle membrane;cytoplasmic vesicle;early endosome membrane;protein-containing complex;VCP-NPL4-UFD1 AAA ATPase complex;sarcolemma;membrane raft;perinuclear region of cytoplasm
• Molecular function: signaling receptor binding;patched binding;structural molecule activity;protein binding;cholesterol binding;peptidase activator activity;enzyme binding;protein kinase binding;protein binding, bridging;protein-containing complex scaffold activity;identical protein binding;ion channel binding;protein heterodimerization activity;Rac GTPase binding;nitric-oxide synthase binding;ATPase binding;inward rectifier potassium channel inhibitor activity