CAV2

protein-coding

caveolin 2, the group of Caveolins

Gene summary

The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462). [provided by RefSeq, May 2011]

MANE transcript

NM_001233.5

Inheritance

ClinVar variants

U:26B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr7:116,287,380-116,508,541

External References & Databases

Ensembl (ENSG00000105971)

Transcript & Mutation Effects

hg38 • Region Span ~221.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amyotrophic lateral sclerosisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0004976

Submitter: ClinGen

Variants in the CAV2 gene have not been reported in relation any disease. CAV2 gene is known to be co-localized with CAV1 gene and has not been associated with any disease independently. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in inheritance pattern and phenotypic variability for these assertions. Therefore, these assertions have been split into the following disease entities: autosomal dominant Amyotrophic lateral Sclerosis (ALS), Pulmonary Hypertension (PPH3), Congenital Lipodystrophy (CGL3) and Familial Lipodystrophy – Type 7 (FPLD7). This curation for autosomal dominant ALS does not include probands from the other reported diseases. Heterozygous missense variants in enhancer regions of the CAV2 gene have been reported till date in individuals with ALS (PMIDs: 33264630). In all instances of literature when available, affected probands with CAV1/CAV2 enhancer variants are identified to have dysregulated caveolar protein expression levels (PMIDs: 33264630, 36937187, 30894019). The maximum score for genetic evidence reached is 3.5 (Limited 0-6). Evidence supporting this gene disease pair also includes experimental data from patient lymphoblastoid cells and and IPSC derived neurons measuring expression of the calveolar protein (33264630, 36937187, 30894019).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CAV2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001233.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	1 clinvar	5
missense			26 clinvar			26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	26	4	1	31

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001233.5	RefSeq	NP_001224.1	3	MANE Select
ENST00000222693.5	Ensembl	ENSP00000222693.4	3	MANE Select
NM_001206747.2	RefSeq	NP_001193676.1	3	Standard
NM_001206748.2	RefSeq	NP_001193677.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

negative regulation of endothelial cell proliferation
positive regulation of endothelial cell proliferation
vesicle fusion
mitochondrion organization
endoplasmic reticulum organization

Molecular Function

structural molecule activity
protein binding
protein kinase binding
protein binding, bridging
protein-containing complex scaffold activity

Cellular Component

Golgi membrane
acrosomal membrane
nucleus
cytoplasm
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222693
Coding exons: 3
Length: 221162
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0450	89	90.2	0.987	0.00000422	1067
Missense (PolyPhen)		35	32.114	1.0899		406
Synonymous	0.145	36	37.1	0.970	0.00000177	310
Loss of Function	1.05	3	5.70	0.527	2.42e-7	65

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000055	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity). {ECO:0000250, ECO:0000269|PubMed:15504032, ECO:0000269|PubMed:18081315}.;

Recessive Scores

pRec: 0.293

Intolerance Scores

LoFtool: 0.228
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.722

Gene Damage Prediction

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