CAV1

Chr 7ARAD

caveolin 1

Also known as: BSCL3, CGL3, LCCNS, MSTP085, PPH3, VIP21

NCBI Gene: 857 ENSG00000105974 UniProt: Q03135 OMIM: 601047

Caveolin-1 is a scaffolding protein that forms caveolae plasma membrane structures and regulates multiple signaling pathways including integrin-FYN coupling and Wnt signaling. Mutations cause congenital generalized lipodystrophy type 3, familial partial lipodystrophy type 7, and primary pulmonary hypertension type 3 with both autosomal recessive and autosomal dominant inheritance patterns. The gene shows tolerance to loss-of-function variants (pLI 0.008, LOEUF 1.31), reflecting the multiple disease mechanisms possible with different variant types.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. Caveolin 1 and caveolin 2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Mutations in this gene have been associated with Berardinelli-Seip congenital lipodystrophy. Alternatively spliced transcripts encode alpha and beta isoforms of caveolin 1.[provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Lipodystrophy, congenital generalized, type 3MIM #612526

Lipodystrophy, familial partial, type 7MIM #606721

Pulmonary hypertension, primary, 3MIM #615343

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

286

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CAV1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.008

Z-score 1.03

OE 0.58 (0.28–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.82 (0.69–0.98)

86 obs / 105.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.28–1.31)

0≤0.351.4

Missense OE?0.82 (0.69–0.98)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 4 / 6.9Missense obs/exp: 86 / 105.3Syn Z: 0.81

Background carrier burden — how many people carry a rare variant somewhere in CAV1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

308 rare PASS variants

Rare truncating (LoF)

1 in 2,600

38 rare PASS variants

Rare synonymous (reference)

1 in 440

82 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CAV1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 1,800
South Asian	~43k	1 in 130	1 in 360
Remaining (unassigned)	~30k	1 in 140	1 in 2,500
European (Finnish)	~27k	1 in 410	1 in 3,800
Admixed American	~22k	1 in 170	1 in 3,300
African / African American	~21k	1 in 150	1 in 1,800
East Asian	~20k	1 in 240	1 in 3,500
Ashkenazi Jewish	~13k	1 in 200	none seen
Middle Eastern	~2,884	1 in 200	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓